Category: Publications

Parent category to all problems relating to the physical aspect of the body

  • Homeopathic Remedies for Headaches

    Guna Oral Remedies

    • GUNA-FLAM (10 drops every 15 minutes in the acute phase; continue with 10 drops 3 times a day for 30-60 days)
    • GUNA-LYMPHO (10 drops 3 times a day for 30-60 days)
    • GUNA-FEM (10 drops 3 times a day for 30-60 days)
    • GUNA-MALE (10 drops 3 times a day for 30-60 days)

    Guna Ampoules 

    Reckeweg Oral Remedies

    Heel Oral Remedies for Headaches

    For chronic headache the remedies indicated should be administered once each daily for a longer period.

    Ampoule Therapy

    Spigelon  (neural, segmental), possibly mixed with Gelsemium-Homaccord – often also indicated with

    and

    Your goal is obviously to eliminate the headaches completely long term.

  • Treating Osteoarthritis of the Knee with a Homeopathic Preparation

    Results of a Randomized, Controlled, Clinical Trial

    in Comparison to Hyaluronic Acid

    ABSTRACT

    This multicentric, randomized, singleblind, controlled study compared the efficacy and tolerance of Zeel® compositum and Hyalart brand of hyaluronic acid in the treatment of patients wich osteoarthritis of the knee. Over the five week course of the study, each patient received either 10 injections of Zeel compositum (two 2 ml intra-articular injections per week) or 5 injections of Hyalartt (one 2 ml intrarticular injection per week). Key parameters were the intensity of pain in the arthritic joint during active movement, and the glnbal assessment nf tolerance, both as reported by the patient. Out of a total of 121 patients, the data on 114 (2 treatment groups of 57 patients each) were suitable for stacistical analysis. Zeel® compositum and Hyalarr® proved to be equally efficacious in treating patients wich either milder or more severe pain. Undesirable incidents occurred in 6 patients receiving Zeel® compositum and in 13 of those receiving Hyalart®.In both treatment groups, the most fre- quencly reported side effects were signs of local inflammation or irritation after the intra-articular injections.

    INTRODUCTION

    Osreoarthritis of the knee is a painful, degenerative joint disease that occurs in approximately 10% of all individuals over the age of 65 and in approximately 2% of the total adult population. At present there is no effective means of treating the cause. Depending on the stage of the illness, however, good therapeutic results can be achieved with non-steroidal anti-inflammatories, corticosteroids, hyaluronic acid, homeopathic remedies, and organ lysates. Age-related cartilage degeneration is a crucial Factor in the development of arthritis, since all bradytrophic tissues due in large part ro the fact that they are poorly supplied with blood vessels are subject to regressive aging processes with increasing loss of elasticity. Because of the chronic and generally progressive nature of the disease,the best possible ratio of therapeutic efficacy to risk of undesirable side effects is a prime consideration in the selection of pharmaceutical cherapy.

    The goal of this multicenter, randomized, controlled, singleblind, clinical equivalence study was to prove the therapeutic efficacy of Zeel® compositum in treating knee arthritis. According to the symptom pictures of its individual ingre- dients (Rhus toxicodendron, Arnica montana, Solanum dulcamara, Sanguinaria canadensis, and Sulphur), Zeel® compositum, a combinacion homeopathic preparation, is appropriate for effectively alleviating arthricic symptonms with little risk. Hyalart® brand of hyaluronic acid (a polysaccharide and a natural component of synovial fluid) was selected as the comparative drug. Controlled studies have demonstrated the therapeutic efficacy of Hyalart in treating arthritis. Because Hyalart®is visibly more viscous than Zeel compositum and because the manufacturer recommends less frequent applications than are recommended for Zeel® compositum, it was not possible to conduct this trial on a strict double-blind basis, so it was conducted as a single-blind study. Additional injections of a placebo to equalize application frequencies berween the two drugs were rejected as unethical.

    Editor’s note: The formula of the complex bomeopathic preparation featured in this study, Zeel® compositum, is not avail- able in the U.S. In the U.S. Zeel is distributed ointment, tablets, and oral vials, all of which contain the same ingredients of Zeel® compositum,plus others.

    METHODOLOGY

    Between July 1994 and February 1995,12 orthopedic physicians in active practice in Germany and Austria accepted a total of 121 patients of boch sexes with primary osteoarthritis of the knee into this clinical trial.

    Criteria for inclusion were:

    presence of primary (idiopathic) arthritis, verified by:

    a typical X-ray (medial narrowing of the joint cavity, peripheral osteo- phyte development, compact ossifi- cation of subchondral bone)

    chronic pain in one or both knee joints for at least three months, with no sign of acure inflammation

    Written statement of patient consent. Criteria for exclusion were:

    • age <35 or>85 years
    • arthritis resulting from prior deforma- tions, injuries, or metabolic causes (secondary arthritis)
    • other ailments with symptoms similar to arthricis of the knece, such as archri- tis of the hip, varicosis, bone and muscle disorders, rheumatoid archritis
    • signs of acute inflammation (acure active arthritis)
    • non-ambulatory or bedridden patients ·patients who stated their intention to change their level of physical activity during the study
    • probable surgical treatment of the arthritic joint in the near furure
    • intra-articular corticosteroid treatment of the arthricic joint within the past 2 months
    • low-grade pain (<75 mm on the 100 mm visual analog scale)
    • a history of allergic reactions to Zeel® compositum or Hyalart®
    • serious liver or kidlney disease
    • long-term treatment wih immuno- suppressives during the last month
    • ongoing concomitant therapy with analgesics/anti-inflammatories

    Random assignment to one of the two

    treatment groups was accomplished with the help of a special EDP program (Rancode,IDV), which also sorted the patients into subgroups on the basis of pain intensity during active movement of the arthritic joint. Less severe pain was defined as 25-60 mm on the VAS-SB, severe pain as 61-100 mm. Treatment proceeded according to the manufactur- ers’ recommendations. Over the five- week course f the study, each patient received eicher 10 injections of Zeele compositum (two 2 ml intra-articular injections per week) or 5 injections of Hyalart® (one 2 ml intra-articular injection per week). To ensure that the parients did not know which medication they were receiving,the physicians were requested to prepare and administer the injections in such a way that the patients could not see the packaging and to make sure that participants in the study were not in the same room at the same time.

    Primary parameters were:

    • subjective experience of pain in the arthritic knee joint during active movement, measured on a standard- ized visual analog scale(VAS) 100 mm in length (0 mm =pain-free,100 mm =worst pain to date)
    • the patients’ final assessment of toler- ance ar the end of five weeks of treat- ment,measured on the 100 mm VAS (0 =extremely poorly tolerated, 100=extremely well tolerated)

    Secondary parameters were:

    • pain in the arthritic knee joint during the night,measured on the 100 mm VAS (0 mm = pain-free,100 mm= worst pain to dare)
    • duration of moming stiffness (in minutes)
    • maximum distancc the patient was capable of wallcing (as a functional criterion for assessing the severity of the arthritis)
    • time required (in seconds) to walk up and down a standard series (one flight) of stairs (relative change)
    • final assessment of efficacy by physician and patienc ac the end of five weeks of rreatment,measured on the 100 mm VAS (0 mm = no improvement,100 mm =extreme improvement)
    • final assessment of tolerance by physician and patient ar the end of five weeks of treatment,measured on che 100 mm VAS (0 mm = cxtremely poorly tolerated,100=extremely well tolerated)
    • drop-out rate in both groups resulting from inadequate product efficacy
    • reporting of undesired side effects dur- ing treatment(recorded weekly)

    All of the compiled data were recorded on standardized questionnaires. The study was conducted in accordance witl the European Union’s Good Clinical Practice guidelines and German and Austrian national laws.

    Data Preparation and Statistical Analysis

    A two-tailed Wilcoxon’s rank-sum test (=0.05 and =0.20) was used to analyze the differences between the treatment groups with regard to efficacy and tolerance. In calculating required sample size, the efficacy or tolerance of the two forms of treatment was assumed to be therapeutically equivalent if the absolute dif- ference in therapeutic efficacy (defined as reduction in pain during active move- ment after five weeks of treatment, as measured on the VAS) or tolerance (defined as final assessment after five weeks of treatment, as measured on the VAS) between Zeel® compositum and Hyalart® was no greater than 33%. Minimum group size was calculated ar nl=n2=51, without including dropouts amounting to approximarely 10%. Comparabilicy of treatment groups with regard to baseline characteristics was cested by means of either the Wilcoxon test (pain during active movement or during the night when the study began) or the chi-square test.(number of affected knee joints); the difference in frequency of side effects was tesred by means of the chi-square tesr. Taking into account the patierics’ subjective experierce of pain intensity during active movcinent when the study began (as per VAS-SB), therapeutic efficacy and tolerance in each trearment group were compared by means of either covariance analysis or the Wilcoxon test (patiencs with more or less severe pain were assigned to subgroups). A descriptive statistical analysis of baseline characteristics and all secondary parameters was performed wich a chosen level of significance of =0.05.

    Results

    In accordance wich the intent-to-treat principle, all available analyzable dara on 114 parients, including dropouts and protocol violators, were used in analyzing efficacy and tolerance. Of a total of 121 randomly selected patients, three did not meer the minimum pain requirement (at least 25 mm on the VAS-SB). Four patients who had been mistakenly treated with both products (in different knees)were studied only with respect to undesired incidents and excluded from the analysis of efficacy, resulting in 114 assessable patients (Table 1). The two treacment groups (n=57) were comparable both with regard to all baseline characteristics (age, gender, height and weight, concomitant illnesses and medications) and with regard to anamnestic data on the artchricis (duration of illness, intensity of pain,and morning stiffness ar the inception of the study, Table 2). In accordance with the exclusion criteria, concomitant use of analgesics and antinflammatories was prohibited. Protocol violations on this count occurred in one patient receiving Zeel® compositum and in three receiving Hyalart®. Other protocol violations were premature termina- tion of therapy for non-medical reasons (one patient), failure to adhere to trear- ment schedule (one parient),and prema- ture termination of therapy because of inadequate improvement (two patients receiving Zeel® compositum and one receiving Hyalart®).

    a) Therapeutic Efficacy

    The patients’ arthritic symptoms clearly decreased both under treatment with Zeel® compositum and under treatment with Hyalart.® In boch treatment groups there was a roughly linear decrease in pain due to active movement of the arthricic joint.This decrease aver- aged 36 mm for Zeel® compositum (from 67 mm to 31 mm) and 37 mm for Hyalart®(from 63 mm to 26 mm).The reduction in nocturnal joint pain fol- lowed a similar pattern, with a linear decrease during treatment (from 33 mm ro 9 mra for Zeel® compositum and from 35″mm to 7 mm for Hyalart). Duration of morning stiffness in the arthricic joint was reduced from 5 min- utes to 2 minutes for Zeel® compositum and to 1 minute for Hyalare®(Table 3). According to analysis of the difference in therapeutic efficacy berween Zeel® compositum and Hyalart® by means of a two-tailed Wilcoxon’s rank-sum test, these two forms of treatment can be seen as therapeutically equivalent (pain during movement: p = 0.4298; pain during the night:p=0.3077;duration of morning stiffness:p=0.9211).An increase in functional ability was associated with pain reduction during treatment.After five weeks of treatment, the percentage of patients who were able to walk more than 1 km increased from 55% to 67% for Zeel® compositum and from 68% to 79% for Hyalart®. In 3 out of 5 pacients in the Zeel® compositum group and 1 out of 3 patients in the Hyalart® group, symptoms improved so much that they were able to do without the cane they had needed when treatment began.The time needed to climb one flight of stairs also decreased by an average of 18% for patients treated with Zeel compositum and by an average of 9% for those treated with Hyalart®.

    Table 1
    Table 2
    Table 3

    The results of the final assessment confirmed the comparable therapeutic efficacy of the two products (Table 4). Noticeable improvement in symptoms was reported for 87.3% of the patients treated with Zeel® compositum and 93.0% of those treared wich Hyalart®.In boch treatment groups, The patients’ subjective assessment was slighdy more favorable than that of the physicians who treated them. VAS values assigned by patients were 2 mm greater for Zeel® compositum and 4 mm greater for Hyalart® than the values assigned by the physicians.In both treatment groups, co-variance analysis reveals that the suc- cess of treatment depends significanly on pain intensity at the inception of the study (p =0.0060).When initial pain was considered as a co-variable, no significant difference between Zeel® compositum and Hyalart which regard to therapeutic success could be derermined (p =0.7555). This means that the effica- cy of Zeel® compositum must be seen as equivalent to that of Hyalart® boch in patients witch less severe pain (25 to 60 mm as per VAS) and in cases of more severe pain (61 to 100 mm as per VAS). The fundamental character of the results is not changed if, instead of conducting che assessment according to the intent- to-treat principle, the analysis comprises only the data on the 103 patients who completed the study according to plan.

    Table 4

    b) Tolerance

    In terms of tolerance, the trend favored Zeel® compositum.A total of 6 patients(11%)treated wich Zeel° compositum and 13 patients (23%) treated with Hyalart® developed undesirable side effects (chi-square test: p=0.079). While receiving twice-weekly injections of Zeel® compositum 3 patients developed low-grade joint effusions that had tapped. Renewed applications of Zeel® compositum induced new effu- sions in 2 of these 3 patients, and as a result treatment was prematurely termi- nated(after 9 injections) in one case. The two other patients completed the study according to plan in spite of intermittent joint effusions. One patient reported a temporary sensation of heaviness in the leg after the first injection of Zeel® composicum Another Zeel® compositum patient terminated treatment prematurely after two weeks because of headaches and insomnia. Two patients from the Zeel® compositum group and 9 from the Hyalart group complained of increased pain in the knee joint after the intra-articular injections; the pain lasted from 3 to 7 days. One patient from the Hyalart® group had to terminate therapy after the first injection because of an allergic reaction (pain, swelling and redness from the knee to the mid thigh). In contrast to Zeel® compositum, no joint effusions were observed in the Hyalart group, but one patient complained of a hot burning sensation in the knee joint that appeared 24 hours after cach of the first two Hyalart®injections and Iasted approximately 24 hours. Another Hyalart® patient reported a mild sensation of pressure and fullness in the joint for about 15 minutes after the third injection. In one patient, nausea and repeated vertigo were experienced after intra-articular applications of Hyalart®. The physicians of two additional patients from the Hyalart® group reported that side effects had appeared but they failed to specify further. In all of these cases, the side effects subsided without medication during the course of the study.

    The final assessment of tolerance (as per VAS) upon conclusion of treatment indicated very good tolerance of both ested products wichout significant differences berween the two treatment groups. According to the Wilcoxon tesc: patients’ assessment of tolerance p=0.1213; physicians’ assessment p=0.7287; in the great majority of cases, the physicians’ assessments coincided with those of their patients. (The difference between physician and pacient assessments was 2mm for both treatment groups; Table 4).

    Discussion

    Many studies restrict themselves to statistically substantiating improvement over the course of therapy in comparison to the starting point (pre-post comparison). However, since symptom patterns do not remain constant over the course of an illness, patients generally tend to see a physician only when the pain has already increased. As a result, there is a high degree of probability that the pain will revert spontaneously to its previous level. This is also known as ‘regression to the mean.” Thus analyses based on pre-post comparisons are not always reliable because, taken by themselves, they cannot separate spontaneous improvement from stricly therapeutic effects. A different route was chosen in the context of this present study, namely comparison of improvement in the two treatment groups at the end of a predefined course of therapy (post-post comparison). The definition of therapeutic equivalence that was used here was not purely statistical but primarily clinical, namely a certain range within which the improvement in one group would be considered equivalent to that in the other. In this study, equivalence was assumed if the maximum difference in decrease in pain between the two groups was no more than 33% (pain at inception of study= 100%). In fact, this investigation showed the difference to be only five percentage points (59% for Hyalart vs. 54% for Zeel® compositum),meaning thac wich regard to therapeutic efficacy, Zeel”compositum and Hyalart” are equivalent. There is a linear correlation between improvemenc in pain and duration of treatment. The criterion ‘pain during movement’ yields a coefficient of r=- 0.80 while the criterion ‘pain during the night’ yields a coefficient of=-0.69. A similarly linear relationship was also found in a recently compleced prospective study in which 446 patients wich knee arthritis were treated with Zeel® compositum.

    In addition, it is especially interesting to note that the therapeutic efficacy of Zeel® compositum was found to be equivalent to that of Hyalart® not only in the subgroup wich less severe pain but also in the group which more severe pain. Analysis of the assessments of functional capacity(climbing stairs, distance patients were able to walk) that also contributed to improving the patients’ quality of life.

    In this trial, a trend in Favor of Zeel® compositum was noted with regard to tolerance. Although Zeel® compositum was injected twice as often as Hyalart and the probabilicy of complications was therefore greater, Zeel® compositum had only half as many undesired incidents. While one patient terminated treatment prematurely because of a suspected allergic reaction after being injected with Hyalart®, no allergic reactions of any kind appeared in the Zeele composirum group.

    The results of this clinical study and of the prospective study of Zeel® compositum confirm the favorable empirical reports of this homeopachic preparation that have accumulated over the years. A 1992 prospective study of Zeel® P (which has 10 more ingredients than Zeel® compositum) involved 1845 patients with osteoarthritis of the knee. That study also documented a significant linear decrease in pain symptoms. Like Zeelr compositum, Zeel® P was also found to be therapeutically effective for mild, moderate, and severe symptoms, wich 93.1% of the patients rating the therapeutic success as positive, i.e. satisfactory to very good.

  • Treatment of Allergic Respiratory Conditions with Antihomotoxic Remedies

    A summary abstract, original by: Werner Frase, M.D.

    Reprint from Medicina Biologica, Vol. 2, April-June 2002, 52-54.

    SUMMARY

    The basis of antihomotoxic preparations in allergic respiratory conditions is to stabilize the mucous membranes, thereby normalizing their response to allergens. In general, an oral treatment combines Tartephedreel, Drosera-Homaccord and Husteel. Seven (7) drops of each in a little water 3x/day before meals is a general protocol. The use of this protocol for bronchial problems contributes a broncodilating effect by acting in a spasmolytic capacity. The frequent use of such a protocol can greatly diminish the need for conventional medicine and reduce the frequency and/or duration of the condition. You will find below a list of recommended preparations along with their respective properties and indications.

    ANTIHOMOTOXIC MEDICATION PROPERTIES & INDICATIONS


    BRONCHALIS-HEEL/BRONKEEL Bronchitis, catarrh, chronic bronchitis
    COENZYME COMP/UBICOENZYME Dysfunction of the Krebs cycle
    DROSERA-HOMACCORD Cough, bronchitis, spasm with cough
    ECHINACEA COMPOSITUM Immune stimulation, bacterial infections
    ENGYSTOL Immune modulator, viral infections
    GALIUM-HEEL Activates immune system in chronic cases
    HISTAMIN-INJEEL Modulates histamine release in allergic mechanism of the mucous membranes
    HUSTEEL Cough from varied pathology, spastic bronchitis
    IGNATIA-HOMACCORD Reduces symptoms, sedative
    MUCOSA COMPOSITUM Drainage of mucous membranes
    PSORINOHEEL/SORINOHEEL Stimulating agent
    TARTEPHEDREEL Bronchial conditions with spasm
    TRAUMEEL Localized inflammation from various etiology
    UBICHINON COMPOSITUM Enzymatic dysfunction, stimulation of oxygen metabolism
    URTICA-INJEEL Conditions of the mucous membranes, urticaria

  • Therapeutic Report BHI Allergy Remedy

    Allergic reactions and symptoms are extremely com- plex in their origins and not yet fully understood.

    Allergies can be divided into three major types:

    1. delayed reaction allergies caused by sensitized lymphocytes
    2. antigen-antibody allergies caused by a reaction between immunoglobulin G (IgG) antibodies and antigens and
    3. atopic or inherited allergies which are characterized by the presence of large amounts of sensitizing antibodies called IgE antibodies.

    Examples of delayed reaction allergies, also called cell-mediated hypersensitivity allergies, include contact dermatitis or skin eruptions resulting from exposure to causative agents such as drugs, chemicals and the toxins of poison oak or poison ivy.

    Antigen-antibody allergies occur when an individual has built up a high titer of antibodies following exposure to a specific antigen.Examples of antigen-antibody reactions include transfusion reactions and autoimmune disease.

    Atopic allergies affect roughly 10% of the population. The hypersensitivity involves the production of excessive amounts of IgE antibodies. Allergens which react specifically in this way include pollen,dust, foods as well as bee,wasp and hornet venoms.Reactions of this type include hay fever, asthma, urticaria (hives) and potentially fatal anaphylaxis. Contact with an allergen by a person with an atopic allergy triggers a local inflammatory reaction with accompanying tis- sue damage.

    At the metabolic crossroads of all these allergic reactions is histamine. An excess of histamine is apparently re- leased when the body comes into contact with substances to which is it sensitive.Histamine acting as a mediator of hypersensitivity triggers the inflammatory process.

    A remedy which lends itself exceptionally well to the antihomotoxic treatment of various allergies is BHI Allergy, which has been specifically formulated for the treatment of allergic reactions and symptoms.

    Focusing Ingredient:

    Histamine hydrochloride 8x:

    specific antiallergy effectiveness

    Accompanying Ingredients:

    Arnica 6x:

    inflammations, tissue traumas, neurodermatitis

    Ignatia amara 6x:

    constrictive sensation in larynx and trachea,cough,dif- ficult breathing,fluent coryza, catarrh

    Lycopodium clavatum 6x:

    throbbing headache, cough, inflammation of the eyes, violent catarrh, difficult breathing, sore throat

    Thuja occidentalis 6x:

    skin inflammations, warts,nasal catarrh, asthma, eczema

    Arctium lappa 8x:

    chronic skin inflammations

    Arsenicum album 8x:

    eczema, itching, skin inflammations

    Acidum formicum 8x:

    stimulating factor for toxin elimination

    Ledum palustre 8x:

    constrictive oppression of the chest,suffocative breathing arrest, cough, painful respiration

    Antimonium crudum 10x:

    affections of the mucous membranes, nasal and bronchial catarrh, eczema, skin eruptions with itching

    Embryo bouis 10x:

    detoxicating factor for all tissues

    Graphites 10x:

    skin disorders with eczematous eruptions, scrofulous affections

    Pix liquida 10x:

    eczemas of the hands, itching, eruptions

    Tellurium metallicum 10x:

    eczema scrofulous conditions, eruptions and pain

    Selenium 12x:

    nasal catarrh, cough with mucus and expectoration, straining in the chest, skin inflammations, blisters, itching

    Sulphur 12x:

    skin conditions, eruptions,mucous membranes of the bronchi,allergic reactions

    Psorinum nosode 15x:

    nosode for skin infections, eczemas and inflammations

    This combination of ingredients works together to mutually strengthen their effects on the histamine metabolismand allergic symptoms.

    The respiratory symptoms associated with allergies such as sneezing,cough, itching, burning watery eyes, catarrh and difficult breathing respond well to treatment with BHI Allergy. Skin inflammations due to chemical or food allergies as well as poison oak or ivy and insect bites and stings may also be treated in this way.

    The recommended dosage is one tablet taken six (6) to ten (10) times daily, or about every two hours at the onset of symptoms.This dosage should then be decreased to three (3) times daily upon improvement. In cases where symptoms are severe due to reexposure to causative agents, BHI Allergy may be administered, one tablet every 8-10 minutes to relieve the immediate discomfort. Once relief is observed, the normal dosage schedule is resumed.

    This remedy combines well with other BHI remedies when,additional symptoms are present. For example:

    Hay fever, catarrh:

    BHI Sinus

    Asthma:

    BHI Asthma

    Skin inflammations:

    BHI Skin

    Healing of skin lesions:

    BHI Hair & Skin

    These accompanying remedies should be administered six (6) to eight (8) times daily, every 2-2/2 hours, alternating with BHI Allergy.

    For example:

    For asthma with difficult breathing administer BHI Asthma upon rising, BHI Allergy one hour later, BHI Asthma one hour following Allergy and so on throughout the waking day until symptoms improve. For acute asthmatic attacks administer one tablet of BHI Asthma every eight (8) minutes until symptoms improve and then return to the previous schedule.

  • Mucosal inflammation syndrome in allergic disease

    Reprint and translated from: Rosales-Estrada M. El syndrome de inflamación
    de las mucosas en la enfermedad alérgica. Revista Colombiana de Pediatría.
    2003;38(3):201-5.

    INTRODUCTION
    It is common to find allergic patients with simultaneous clinical signs or symptoms of the respiratory and/or gastrointestinal and/or genitourinary mucosal membranes. In the present study the common denominator was allergic rhinitis. Simultaneous clinical involvement, circumscribed to the aforementioned mucosal tissues (mucosae) clearly suggests common physiopathological factors in allergic disease; accordingly, alterations of one type of membrane affect the others, or alterations of two or more mucosae may be explained on the basis of a common mechanism.

    Hypothesis. Allergic disease can give rise to simultaneous clinical manifestations of the respiratory, gastrointestinal and genitourinary mucosal membranes.

    Objective. To determine whether allergic disease can give rise to simultaneous clinical manifestations of these mucosae.

    Summary. Patients who have allergies can have simultaneous respiratory, digestive and genitourinary mucosal disease. I performed a retrospective study in 30 patients; 24 children and 6 women. The children were between 5 and 9 years old, and the women were between 26 to 40 years old. All of them suffer from allergic diseases.

    Results. 100% had clinical respiratory diseases like rhinitis, asthma, arithenoids or vocal cord inflammation, tonsillectomy, and/or frequent respiratory viral infections. 100% of the patients had clinical digestive diseases such as gastro-esophageal reflux, gastroduodenitis, constipation and diarrhea. 87% of the female patients had clinical genitourinary diseases such as vulvovaginitis and urinary infections.

    The results of this study are very important because they provide information regarding the clinical behaviour of allergic diseases, which can be systemic. According to this concept, its treatment should be holistic and individual because each patient can have one or more mucosae involved. The most recent articles of medical literature refer to rhinitis and asthma only as a like process.

    MATERIALS AND METHODS
    A retrospective analysis was made of 30 deliberately selected allergic patients with clinical manifestations of allergic rhinitis that coincided with clinical manifestations of the respiratory and/or gastrointestinal and/or genitourinary mucosal membranes. These clinical manifestations were: asthma, sinusitis, otitis media, acute and recurrent viral respiratory infections, adenotonsillar hypertrophy, inflammation of the vocal cords and arytenoiditis, esophagitis, gastroesophageal reflux (GERD), gastritis, duodenitis, diarrhea, constipation, vaginitis and urinary infections.

    The study series comprised 24 children and 6 adult women. Of the pediatric patients, 10 were girls and 14 were boys. The patient age varied from 5-9 years among the children and from 26-40 years in the case of the adults. Three of the women were nulliparous. The study period was from April 30, 2002 to April 30, 2003.

    Allergic patient classification was based on an evident clinical history of rhinitis, with or without simultaneous asthma and/or total immunoglobulin E (IgE) levels above normal or specific IgE positivity for a given antigen. Clinical antecedents of adenoid removal or tonsillectomy in a large proportion of cases contributed to establish the diagnosis. Thus, the sum of these clinical events undoubtedly would classify these patients as allergic subjects.

    The definition of rhinitis was based on a clinical history of abnormally increased and chronic nasal itching, marked sneezing particularly in the morning, nasal congestion and rhinorrhea of variable intensity according to the severity of the clinical process. Almost all these patients had previously used local steroids applied to the nasal mucosa, prescribed by a physician unrelated to the
    present study.

    Asthmatic patients in turn were defined as those with two or more asthmatic episodes a year on average, in the previous three years, with frequent beta-2-adrenergic and/or inhalatory steroid use.


    Esophago- and/or gastro- and/or duodenitis were diagnosed in the presence of endoscopic and histological findings corresponding to such disorders.

    Recurrent acute viral respiratory infection (ARI) was diagnosed when the patient suffered one or more infections a month.

    Clinical gastritis in turn was defined by clinical signs of acute gastritis – the latter being established by acute epigastric pain accompanied or not by vomiting and relief following antacid administration.

    Chronic cough was defined as cough persisting for more than 20 days in different episodes, with a cause not different from allergy of the upper airways.

    Gastroesophageal reflux (GERD) in turn was diagnosed by gammagraphy or a history of chronic vomiting in a child, or – in the case of adults – chronic heartburn.

    Arytenoiditis and inflammation of the vocal cords was accepted when laryngoscopy confirmed inflammation of these structures.

    Mucosal inflammation index

    Chronic diarrhea was defined as two or more daily depositions, with diarrheic consistency on one or more occasions – all with colic type abdominal pain.


    Constipation was defined as an absence of bowel movement for over 48 hours, with hard stools and a large fecal bolus.

    Vulvovaginitis was described as an episode of vaginal secretion, itching or inflammation of the skin of the vulva and vaginal mucosa.

    Urinary infection in turn was considered for those patients presenting at least one episode of clinical signs and symptoms of urinary infection and positive urine culture for a microorganism known to cause such disorders (bacterial count: 100,000 CFUs or more).

    Likewise, 100% had clinical manifestations of the gastrointestinal mucosa. These manifestations may or may not correspond to allergic physiopathological processes of the membranes. Many of these patients presented clinical signs and symptoms of gastritis in the presence of acute respiratory infection (ARI); 5 of them presented gastric ulcer as established at endoscopy, coinciding with an acute episode of viral respiratory infection.


    On the other hand, 61.9% of the female patients, regardless of age, showed clinical alterations of these mucosae, manifesting as vulvovaginitis and/or urinary infection.

    CONCLUSION
    The selected allergic patients with clinical manifestations of the respiratory tract were seen to possibly present simultaneous alterations of the gastrointestinal and/or genitourinary mucosal membranes.

    DISCUSSION
    The following syndromic manifestations simultaneously affect the mucosal membranes of the respiratory and/or gastrointestinal and/or genitourinary tracts, and partially or completely confirm the different clinical manifestations of MUCOSAL INFLAMMATION SYNDROME, as described for the first time in the present article. These observations were made in allergic outpatients or allergic individuals admitted to hospital, and their detection merits attention and sensitivity on the part of the supervising physician.

    1. Girls with sinusitis and/or allergic rhinitis and/or pharyngitis, with concomitant vaginitis. Eventual ascending urinary tract infection.
    2. Nursing infant (age under 3 months) with gastroesophageal reflux (GERD) (or underlying gastroenteritis) and nasal congestion (noisy nasal breathing) – this latter symptom often being observed before manifestations of GERD become apparent.
    3. Rhinitis, sinusitis and asthma.
    4. Upper respiratory tract allergy and esophago-gastroduodenitis.
    5. Acute viral respiratory tract infection and gastritis and/or exacerbation of gastritis.
    6. Immediate recurrence of GERD (or underlying gastroenteritis), associated with acute viral respiratory infections.
    7. Sinusitis and soft stools with mucus and sometimes of a foul-smelling nature, in children under three years of age.
    8. Acute viral respiratory tract infections with soft stools, and sometimes diarrhea.
    9. Concurrence of tonsillitis with right iliac fossa pain simulating appendicitis or diffuse abdominal pain.
    10. Viral respiratory infections and so-called mesenteric adenitis (diffuse abdominal pain concomitant to viral respiratory infection).
    11. GERD (or underlying gastroenteritis) and chronic cough and/or asthma.
    12. GERD and recurrent airway infections.
    13. Geographic tongue and manifestations of upper respiratory allergy and/or gastroduodenitis.
    14. Reappearance of geographic tongue with acute viral respiratory infections.
    15. Posterior laryngitis (edema, leveling and erythema of the inter-arytenoid mucosa) and edema of Reinke (vocal cord edema),
      associated with GERD.
    16. Urinary infection and/or vulvovaginitis associated with constipation.
    17. Urinary infection and/or vulvovaginitis associated with allergic enteropathy.
    18. Endometriosis in allergic women and allergic enteropathy and/or constipation.
    19. While GERD of the nursing infant (generally under 6 months of age) reflects gastrointestinal mucosal disorders, it has been seen to exacerbate if the mother consumes dairy products, suffers inflammatory enteric disease (constipation, diarrhea), asthma crises, or acute viral respiratory infections.
      • The medical literature reports the partial concurrence of these manifestations:
        • 77% of the adult asthmatic population experience symptoms of GERD.
        • 43% of asthmatic patients subjected to digestive tract endoscopy present esophagitis or Barrett’s esophagus.
        • 20% of children with rhinitis develop asthma.
        • 50% of children with asthma develop rhinitis.
        • Marked association of sinusitis, asthma, laryngitis, pneumonia and bronchiectasia in patients with GERD (patients aged 2-18 years).
        • Clinical association of tonsillitis and right iliac fossa pain simulating acute appendicitis (involving patients needlessly subjected
        to appendectomy). The importance of focusing attention on the global involvement of the mucosal membranes in a given
        patient is that the diagnostic and management approach should be holistic and individualized.
        A lack of response to treatment on the part of pathology related to a given mucosal membrane in the context of allergic disease is seen
        on a daily basis in medical practice when necessary attention is not focused on other simultaneously affected mucosal membranes. The
        following may serve as examples:

    A lack of surgical intervention to correct important adenoid hypertrophy implies frequent respiratory infections (viral, otitis,
    sinusitis).

    1. Torpid course of asthma in patients with uncontrolled GERD (or underlying gastroenteritis).
    2. Acute respiratory infections and the presence of GERD (or underlying gastroenteritis).
    3. A lack of response in allergic patients with uncontrolled rhinitis.
    4. Persistent asthma due to undiagnosed bacterial sinusitis.
    5. Persistence of vaginal secretion and/or urinary infections in patients with constipation or allergic enteropathy.

    In order to begin to modify old paradigms, allergic disease seen from this perspective would not be exclusive to the different subspecialties, determined by the affected body organ. In effect, such conditions could be treated by all physicians, regardless of their specialty, provided thorough knowledge is gained in all spheres where allergy as a systemic disorder produces its devastating effects. Neglect in this context would be a sign of incompetence.

    STUDY

    As an example, an ear, nose and throat (ENT) specialist could not treat rhinitis if the intestinal alterations are not first dealt with. Gynecologists or urologists likewise would not be able to treat a large percentage of cases of vulvovaginitis and urinary tract infections without first treating the respiratory allergies and intestinal disorders. In turn, pneumologists would not diagnose gastritis if not intentionally explored. The same considerations apply to the other medical specialties that deal with allergic processes.


    This clinical approach involving physiopathological dependency of the mucosae in allergic disease would fully reorientate the current treatment established by conventional medicine; each mucosal membrane deals with somewhat different immunological information, though with crossed immune data among different membranes. As an example, a food allergen can produce digestive tract and respiratory symptoms at the same time.


    Food allergies can coincide with allergy produced by aeroallergens in up to 70% of cases, which increases the possibility of crossreactions between foods with aeroallergens. This data implicates the intestine as an important antigen generating source – a fact that must be taken into account when treating an allergic patient, regardless of where the allergic process manifests. It is our experience that once a patient starts a correct diet, with good intestinal hygiene and environmental control, allergic processes largely disappear.


    Another mistake in medical practice is to consider these symptoms as a disease. Such manifestations are actually symptoms or signs of allergic disease, and the correct diagnosis of an allergic patient should be based on the following premises: allergic disease with manifestations of esophagitis, gastritis, rhinitis, asthma, vulvovaginitis, etc. The practice of considering an organ isolatedly from the rest of the organism fails to take into account that the mucosal membranes share immunological information, and that alterations of one membrane can affect others.


    Lastly, another aspect that deserves mention on the basis of the findings of the present study is that ascending urinary tract infection and vulvovaginitis may be related to alterations of nearby mucosal membranes – such as constipation or allergic enteropathy – or more distant mucosae, such as in the case of allergic rhinosinusitis. A number of studies already mention allergic disease as a cause of vulvovaginitis, and even establish a relation to dust mite allergy.10 In my opinion, this problem is very common, though the medical literature does not yet report the situation as such.

    It is hoped that the present study may serve as motivation for investigators to clarify the prevalence of this syndrome in allergic disease, to establish a new definition for the latter, and to explore the association between allergic pathology and other mucosal disorders such as GERD in the adult, vesicoureteral reflux, interstitial cystitis in the adult, constipation and endometriosis.

    As a general conclusion, I am of the opinion that a clinical syndrome exists in allergic disease, which from the physiopathological perspective may partially or fully implicate the respiratory, gastrointestinal and genitourinary tracts, and that the medical literature has not yet recognized its relevance.

    The scientific bases explaining the physiopathology of mucosal inflammation syndrome in allergic disease are based on the new concept of modern psycho-neuro-endocrino-immunology, which we hope to develop in the following issue pending publication.


    The latest publications referring to allergies only view rhinitis and asthma as manifestations of one same process. The corroboration by other investigators of the simultaneous involvement of the mucosal membranes in the allergic patient would help confirm a new definition of allergic disease, and thus also promote a new approach to management.

  • Trio of Homeopathy

    Short Symptomatic IndexTrioRemedy 1Remedy 2Remedy 3
    All gone sensation in chestTRIO-1Digitalis Phosphorous Stannum Met
    All gone sensation in abdomenTRIO-2Phosphorous Sepia Stannum Met
    Aphasia during singing or talkingTRIO-3Argentum Nitricum Arum Triph Causticum
    Bed feels hardTRIO-4Arnica Baptisia Pyrogenium
    Bites (poisoned stage), Insects ofTRIO-5Gentiana Lutea Ledum Pal Staphisagria
    Bites Cats ofTRIO-6Hepar Sulph Ledum Pal Silicea
    Bites Dogs ofTRIO-7Chromic Acid Lachesis Lyssin
    Bites Mad dogs of (Rabies)TRIO-8Belladonna Cantharis Lyssin
    Bites Snakes ofTRIO-9Ars Album Lachesis Ledum
    Bites Spiders ofTRIO-10Cedron Lachesis Tarentula Cub
    Burning (in general)TRIO-11Ars Album Phosphorous Sulphur
    Burning in solesTRIO-12Chamomilla Medorrhinum Sulphur
    CatharticsTRIO-13Aloe Soc Croton Tig Podophyllum
    CholeraTRIO-14Camphor Cuprum Met Veratrum Alb
    Chronic rheumatismTRIO-15Causticum Rhus Tox Sulphur
    ClimactericTRIO-16Graphites Lachesis Psorinum
    Collapse stageTRIO-17Ars Album Camphor Carbo Veg
    Coma with renal failureTRIO-18Apis Mel Cantharis Merc Cor
    CondylomataTRIO-19Nitric Acid Staphisagria Thuja
    ConvulsionsTRIO-20Causticum Cicutaver Cuprum Met
    Cough, Caused by least exposure of body parts to coldTRIO-21Baryta Carb Hepar Sulph Rhus Tox
    Cough, Drinking, amelTRIO-22Causticum Coccus Cacti Spongia
    Cough, During sleepTRIO-23Chamomilla Kali Carb Lachesis
    Cough, While eatingTRIO-24Kali Bich Nux Vomica Thuja
    Cough, 3 A.M aggravationTRIO-25Antim Tart Kali Carb Sambucus
    Cough, 2 A.M aggravationTRIO-26Ars Album Kaliars Kali Carb
    Croup coughTRIO-27Aconite Nap Hepar Sulph Spongia
    Damp weather, ailments fromTRIO-28Dulcamara Natrum Sulph Nux Moschata
    Death desireTRIO-29Aurum Met Laccan Sulphur
    DeliriumTRIO-30Belladonna Hyoscyamus Stramonium
    DiarrhoeaTRIO-31Aloe Soc Gambogia Gratiola
    Diarrhoea, morningTRIO-32Aloe Soc Natrum Sulph Sulphur
    Dread of downward motionTRIO-33Borax Gelsemium Sanicula
    Drooping of eyelidsTRIO-34Causticum Gelsemium Sepia
    Dust aggravation (in general)TRIO-35Bromium Drosera Lyssinum
    FlatulenceTRIO-36Carbo Veg China Lycopodium
    Foetid urineTRIO-37Benzoic Acid Nitric Acid Sepia
    Gouty mucous dischargeTRIO-38Argentum Nit Hydrastis Kali Bichrom
    HaemorrhageTRIO-39Erigeron Millefolium Trillium
    Hands upon chest during coughingTRIO-40Arnica Bryonia Alba Drosera
    Hard tumorsTRIO-41Calc Fluor Conium Hecla Lava
    HopefulTRIO-42Merc Sol Staphisagria Tuberculinum
    Hyper-aesthesia Cruelty, hearing ofTRIO-43Calc Carb Carcinocin Causticum
    Hyper-aesthesia Drugs, fromTRIO-44Nux Vomica Pulsatilla Nig Sulphur
    Hyper-aesthesia, Fever duringTRIO-45Coffea Cruda Nux Vomica Pulsatilla Nig
    Hyper-aesthesia, Light to – TRIO-46Belladonna Nux Vomica Phosphorous
    Hyper-aesthesia, Music toTRIO-47Natrum Carb Nux Vomica Sepia
    Hyper-aesthesia, Odors toTRIO-48Colchicum Nux Vomica Sepia
    Hyper-aesthesia, Pain toTRIO-49Chamomilla Coffea Cruda Hepar Sulph
    Hyper-aesthesia, Taste toTRIO-50China Coffea Cruda Lycopodium
    Hyper-aesthesia, Touch toTRIO-51Aconite Nap Belladonna Lachesis
    Least touching causes violent excitement of sexual organsTRIO-52Murex Per Origanum Zincum Met
    Liver diseasesTRIO-53Cardus Mar Chelidonium Leptandra
    MasturbationTRIO-54Buforana Platina Staphisagria
    MeningitisTRIO-55Apis Mel Helleborous Stramonium
    Nausea, Children, inTRIO-56Chamomilla Ipecacuanha Rheum
    Nausea, Church,inTRIO-57Ars Album Kali Carb Pulsatilla
    Nausea, Closing eyes, aggravatesTRIO-58Lachesis Theridion Thuja Occ
    Nausea, Cold, after taking, aggravatesTRIO-59Dulcamara Nux Vomica Ipecacuanha
    Nausea, Cold,Becoming afterTRIO-60Cocculus Ind Hepar Sulph Kali Carb
    Nausea, Delivery duringTRIO-61Cocculus Ind Ipecacuanha Pulsatilla
    Nausea, Disordered stomach, fromTRIO-62Ipecacuanha Nux Vomica Pulsatilla
    Nausea, Drunkards,inTRIO-63Ars Album Kali Bich Lachesis
    Nausea, Eating after, amelioratesTRIO-64Ferrum Met Kali Bich Sepia
    Nausea, Fats, after eatingTRIO-65Ars Album Drosera Pulsatilla
    Nausea, Food, looking atTRIO-66Colchicum Kali Bich Sulphur
    Nausea, Food, smell ofTRIO-67Colchicum Ipecacuanha Sepia
    Nausea, Food, thought ofTRIO-68Cocculus Ind Colchicum Sepia
    Nausea, Odours fromTRIO-69Colchicum Phos Acid Sepia
    OffensivenessTRIO-70Baptisia Tinc Merc Sol Psorinum
    Offensive breatheTRIO-71Kali Phos Kreosotum Merc Sol
    PainTRIO-72Belladonna Chamomilla Coffea Cruda
    Pain, Cramping painTRIO-73Colocynthis Dioscorea Mag Phos
    Pain, Nervous painTRIO-74Belladonna Chamomilla Coffea Cruda
    Pain, Radiating pain in abdomenTRIO-75Berberis Vulg Mag Phos Plumbum Met
    Pain under scapulaTRIO-76Calcarea Carb Chelidonium Chenopodium
    Painful urinationTRIO-77Cantharis Merc Sol Sarsaparilla
    PalpitationTRIO-78Digitalis Cactus Kalmia
    Paralysis, Right sidedTRIO-79Causticum Rhus Tox Thuja
    Paralysis, Left sidedTRIO-80Lachesis Nux Vomica Rhus Tox
    Paralysis, Single parts,ofTRIO-81Ars Album Causticum Dulcamara
    Pneumonia, Children, ofTRIO-82Antim Tart Ipecacuanha Kali Carb
    Pneumonia, Drunkards, ofTRIO-83Hyoscyamus Nux Vomica Opium
    Pneumonia, First stageTRIO-84Aconite Nap Bryonia Alba Sulphur
    Pneumonia, Old peoples, ofTRIO-85Aconite Nap Ferrum Phos Merc Sol
    PoliomyelitisTRIO-86Causticum Gelsemium Plumbum Met
    Prolapsus of uterus (sensation of)TRIO-87Lilium Tig Murex Per Sepia
    Prolapsus of rectumTRIO-88Ignatia Podophyllum Ruta
    Profuse expectorationTRIO-89Hepar Sulph Pulsatilla Nig Stannum Met
    Prostration, Cares, fromTRIO-90Cocculus Ind Phos Acid Picric Acid
    Prostration, Coition, afterTRIO-91Calc Carb Sepia Staphisagria
    Prostration, Grief, afterTRIO-92Ignatia Lecithin Phos Acid
    Prostration, Mental exertion, fromTRIO-93Anacardium Orient Kali Phos Kali Sulph
    Prostration, Reading, fromTRIO-94Aurum Met Picric Acid Silicea
    Prostration, Sexual excesses, afterTRIO-95Agnuscastus Phos Acid Picric Acid
    Purulent expectorationTRIO-96Kali Carb Lycopodium Silicea
    Rattling coughTRIO-97Antim Tart Hepar Sulph Ipecacuanha
    RestlessnessTRIO-98Aconite Nap Ars Album Rhus Tox
    Reverse periostalsisTRIO-99Nux Vomica Opium Plumbum Met
    Sensitiveness of nose from inspirationTRIO-100Hepar Sulph Nux Vomica Phosphorous
    SleepinessTRIO-101Antim Tart Gelsemium Nux Moschata
    SorenessTRIO-102Arnica Eupatorium Perf Rhus Tox
    Spinal disordersTRIO-103Cocculus Ind Nux Vomica Phosphorous
    Sticky, pus dischargesTRIO-104Calc Sulph Graphites Hepar Sulph
    Stitching painTRIO-105Bryonia Alba Kali Carb Natrum Sulph
    Stool, during flatusTRIO-106Aloe Soc Oleander Phos Acid
    Stringy expectorationTRIO-107Coccus Cacti Hydrastis Kali Bich
    StuporTRIO-108Nux Moschata Opium Phosphoric Acid
    Suicidal dispositionTRIO-109Aurum Met Natrum Sulph Psorinum
    Suppuration, on slightest injuryTRIO-110Hepar Sulph Merc Sol Silicea
    Sweating solesTRIO-111Ammon Mur Nitric Acid Silicea
    Sweating soles, OffensiveTRIO-112Petroleum Plumbum Met Silicea
    Thirstless with dryness of mouthTRIO-113Bryonia Alba Nux Moschata Pulsatilla Nig
    Wandering pain, ExtremitiesTRIO-114Kali Sulph Laccan Pulsatilla Nig
    Wandering pain, JointsTRIO-115Kali Bich Laccan Pulsatilla Nig
    Warm applications, amel (in general)TRIO-116Ars Album Kali Phos Mag Phos
    WartsTRIO-117Nitric Acid Causticum Dulcamara
    Weepiness in childrenTRIO-118Chamomilla Lycopodium Pulsatilla Nig
    Weepines, NightTRIO-119Borax Lycopodium Psorinum
    Weepines, Will is not fulfilled, whenTRIO-120Cina Dulcamara Spongia
    Whooping coughTRIO-121Carbo Veg Drosera Kali Sulph

  • A randomized equivalence trial comparing the efficacy and safety of a homeopathic nasal spray with cromolyn sodium spray in the treatment of seasonal allergic rhinitis

    Randomisierte Äquivalenzstudie zum Vergleich der Wirksamkeit und Verträglichkeit eines homöopathischen Nasensprays mit einem Cromoglicinsäure-Nasenspray bei der Behandlung der saisonalen allergischen Rhinitis

    Michael Weiser’, Lutz H. Gegenheimer, Peter Klein3

    1 Department of Antihomotoxic Medicine, Baden-Baden

    2 Reporting and Consulting Services in Clinical Pharmacology, Mannheim

    3 Datenservice Eva Hoenig GmbH, Rohrbach

    Address of corresponding author:.

    Dr. Michael Weiser

    Department of Antihomotoxic Medicine

    Dr. -Reckeweg-Str. 2-4, D 76532 Baden-Baden, Germany

    KEY WORDS
    Homeopathy, cromolyn sodium, clinical study, seasonal allergic rhinitis

    SUMMARY
    Background: The. objective of the clinical. study was to investigate the-efficacy and
    tolerance of a homeopathic nasal spray in cases of hay fever (seasonal allergic rhinitis) in comparison with the conventional intranasal. cromolyn sodium therapy. Patients, and methods: In total 146 out-patients with symptoms of hay fever were enrolled into the clinical study(randomized, , double-blind, equivalence-trial)(time of treatment: 42 days). The homeopathic remedy (Luffa comp. -Heel'" Nasal Spray, dosage: 0. 14 ml per application, 4 times a day/naris) consisted of a fixed combination made up of Luffa operculata, Galphimia glauca, histamine, and sulfur. The main outcome measure of the efficacy was the quality of life as. measured by means of the Rhinoconjunctivitis Quality of Life-Questionnaire (RQLQ). The tolerance of the trial medication was registered by means of global assessment, rhinoscopy, recording of adverse events and with the aid of vital and laboratory parameters.

    Results: The results of the study demonstrate a quick and lasting effect of the treatment that was independent from the medication applied and produced a' nearly complete remission of the hay fever symptoms. The RQLQ global score changed significantly in the course of the treatment indicating therapeutic equivalence between the two forms of treatment. Adverse systemic effects did not occur. Local adverse events appeared in three patients.

    Conclusions: The . study proved that for the treatment of hay fever the homeopathic nasal spray is as efficient and well tolerable as the conventional therapy with cromolyn sodium.

    INTRODUCTION
    Seasonal allergic rhinitis (hay fever) is widespread among general·population. The prevalence of the disease in Central Europe is estimated to range around 20% [1, 2]. Seasonal allergic rhinitis is provoked by pollen from various plants. Via an immunological mechanism·they cause inflammation of the nasal, mucosa which is associated with characteristic symptoms including nasal hypersecretion and obstruction, mucosal erythema and enema, sneezing, and itchy. nose. Accompanying symptoms of allergic conjunctivitis, fatigue, and headache may in addition. impair subjective well-being. The intensity of these symptoms. depends. on the. extent of antigen exposure and is thus season-specific. Concentrations of tree pollens are generally highest in spring, while grass pollens are more abundant in summer and weed pollens in late summer and early autumn [3].

    Since pollen allergens are ubiquitous and difficult to avoid, and. since desensitization may take years, is not always successful, and carries risks (e. g. anaphylaxis), symptomatic

    treatment of hay fever 'is often. necessary. Conventional medicine offers several well-established therapeutic strategies, such as intranasal cromolyn sodium, intranasal or oral antihistamines as well as intranasal and if necessary oral corticosteroids.

    A homeopathic remedy for seasonal allergic rhinitis was developed as a therapeutic option comprised of Luffa operculata, Galphimia, glauca, histamine, and sulfur. The constituents of this remedy (manufactured and marketed as. Luffa comp. -Heel" Nasal.


    Spray, by Heel GmbH, Baden-Baden, Germany)have accordingly been co-ordinated in such a manner that they effectively complement each other in their therapeutic action: Gallophilia glauca and histamine are two agents whose therapeutic effectiveness is well known, especially for affections of the skin and mucous membranes. Their therapeutic action is enhanced by sulfur as stimulation (reversal) remedy for chronic and inflammatory diseases and Luffa. operculata, indicated for common colds and allergic affections of the respiratory organs such as hay fever and asthma. The homeopathic nasal spray used in this study contains a fixed combination of Luffa operculata and Galphimia glauca in dilutions 4X, 12X, and 30X and histamine and sulfur in dilutions 12X, , 30X, and 200X (the degree of dilution is indicated by an X, which indicates the rati) of 1. part of active ingredient to. 10 parts of diluent. A"1X" indicates a ratio of 1:10, a "2X" indicates a dilution of 1:100, etc.（4, 5]). In a meta-analysis of seven randomized double-blind trials Galphimia glauca proved superior to placebo' in reducing ocular hay fever symptoms; the response rates of Galphimia glauca were estimated to he similar to those specified for conventional antihistamines [6]. The present study was designed to compare uffa comp. -Heel" Nasal Spray with a nasal spray containing 20 mg/ml cromolyn sodium (usual concentration marketed in Germany) with respect to both efficacy and tolerance in the therapy of seasonal allergic rhinitis.

    PATIENTS AND METHODS

    The study protocol was approved by an independent Ethics Committee (Ethikkommittee der Landesärztekammer Rheinland-Pfalz) and implemented in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. All patients participating in the study gave written informed consent. The study was performed according to a parallel group design.Within each study.center the patients were evenly randomized to cromolyn sodium or homeopathic treatment (because the number of patients recruited-by each center could not be estimated apriori, randomization was performed in blocks of 2). In a double-blind manner, one spray, about 0.14 ml, was administered 4 times daily into each nostril. During acute exacerbation of symptoms, up to 8 sprays per nostril were allowed. To ensure blinded conditions both compounds (representing aqueous solutions and containing benzalkonium chloride as a preservative) were dispensed in identical,neutral bottles (eventually by direct and immediate comparison the preparations were distinguishable by.taste).Sealed envelopes containing the code for each patient were supplied by the sponsor to the investigators. It was only allowed to break the individual random code in cases of emergency (the code was broken after data entry and the decision about protocol deviations/evaluations groups through the responsible biostatician). Patients were recruited from different study centers located in the same geographic region(Upper Rhine Valley of Germany) during the hay fever seasons of 1996 and 1997. They were to be seen for assessment of baseline status (visit 1), and after 7±1,14±2,28±3 and 42±3 consecutive days of treatment (visits 2 to 5). The treatment duration of 6 weeks was chosen based on clinical experience; it was short enough to ensure that in the majority of patients antigenic exposure persisted throughout their participation in the trial and long enough to compensate for variation of weather conditions affecting pollen concentrations.

    Study Population

    Male and female out-patients,.aged 18 to 60 years, suffering from seasonal allergic rhinitis as diagnosed by RAST (lgE-antibody measurement),'scratch or skin-prick test were eligible for the study. Patients were excluded if they had a diagnosis of perennial allergic rhinitis or infectious diseases of the upper respiratory tract; known hypersensitivity to the study medication; treatment with drugs containing cromolyn sodium or corticosteroids within two' weeks of the: study start; treatment with antihistamines or alpha-sympathomimetics within 24 hours of. the study start; or regular use of anti-inflammatory agents and analgesics. No pregnant or nursing women were accepted. In addition, to reduce the risk of dropouts due to the need for prohibited co-medication, patients were disqualified from study. participation if they had a history of emergency treatment of allergic symptoms or of regular treatment of hay fever with oral corticosteroids and/or antihistamines during the past two years (by this restriction an overrepresentation of patients suffering from mild to moderate symptoms was favoured). Prohibited co-medication encompassed any compounds used for treatment of hay fever (even if they were, not prescribed for this indication) other than the respective study. drug (in particular. alpha-sympathomimetics, corticosteroids and antihistamines); this also applied to the therapy of ocular hay fever symptoms.

    Assessments

    Drug efficacy was assessed primarily with a validated self-rating (patient) instrument, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)[7,8].The German adaptation of the questionnaire [9].was completed at visits 1 through 5. The questionnaire consists of 28 items that pertain to particular symptoms and their practical consequences for daily life. The items are subdivided into seven ·domains: 1) nasal symptoms (4 items); 2) ocular symptoms (4 items); 3) general non-hay fever symptoms (7 items); 4) sleep disturbances (3 items); 5) practical problems associated with rhinoconjunctivitis, such as carrying tissues and nose blowing (3 items); 6) implications on 3 personal activities named by the patient at the outset (3 items); and 7) emotional symptoms, such as frustration (4 items). The particular items are represented by questions of the general form 'how troubled have you been by (e.g. stuffy nose)' that refer to the preceding week. Patients rated the degree (physical symptoms and their practical implications) or the temporal extension (emotional symptoms) of their, subjective impairment on a 7-point scale ranging from 0 (not troubled at all; none of the time) to 6 (extremely troublesome; all the time). Domain-specific scores were obtained by averaging the numerical values of the pertinent items. Division of the sum of the domain-specific scores by the number of domains yielded an overall score reflecting the quality of life of patients suffering from seasonal allergic rhinitis. This overall score, ranging from 0 to 6 (highest to lowest quality) was the main efficacy parameter.

    In addition, efficacy was measured by using the domain-specific subscores and the global assessment of the present quality of Life on a visual analog scale that ranged from 0mm.("could not be worse") to 100 mm ("could not be better") at visits 1 through 5.The global al assessment of therapeutic efficacy at the end of treatment was measured by both patient and investigator on a 4-point scale ranging from "excellent" to "poor."

    Local tolerance was assessed at visits 2 through 5 by rhinoscopic examination（using a nasal speculum) of the nasal mucosa for erythema, edema, and dryness of nose. These symptoms were classified on 'a 5-point scale ranging from "missing" to "strong." Patients also rated nasal pruritus, urge of sneezing, and feelings of burning and dryness of nose on 5-category scales according to frequency (from-"never" to "after each administration") and intensity (from "slight" to "very strong").

    At the end of treatment, tolerance was globally assessed by both the patient and the investigator on a 4-point scale ranging from 1 (very good)to 4 (poor).Physicians performed drug safety evaluations based on the incidence of adverse events reported at visits 2 through 5 and monitoring of vital signs and laboratory status, such as hematology, clinical chemistry, and urinalysis at visits 1 and 5.

    Statistical Evaluation

    To show the non-inferiority of the homeopathic group according to the "Statistical Principles of Clinical Trials" a one-sided (1-a). confidence interval was. used. Equivalence was inferred if the lower limit of the interval was larger than the equivalence limit. For the main efficacy parameter (overall.RQLQ scores at visits 2 through 5) ·a generalized Wilcoxon-Mann-Whitney procedure was used (directional test for stochastic. ordered alternatives according to Wei and Lachin).[10-12].A one-sided equivalence test can be formulated using the Mann-Whitney statistic P(X<Y)+0.5P(X=Y)[abbreviated as P(X<Y)].It is a measure of stochastic superiority. Values lower then 0.5 denote inferiority and values higher then 0.5 denote superiority. The test for one-sided equivalence ("equivalent “or＂better") can be performed by means of .a one-sided (1-a) confidence interval (Cl) in the following way If the lower bound of the Cl is larger then 0.36 (corresponding to a medium- sized inferiority according to Cohen [13]) the null hypothesis of inferiority. can be rejected（null hypothesis Ho:P(X<Y)≤0.36; alternative hypothesis HA:P(X<Y)>0:36).

    Analysis of all randomized patients may be biased toward demonstrating equivalence. For this reason the first-line analysis for efficacy was a per-protocol analysis considering dropout rates and major study protocol deviations. Missing values because of dropouts were replaced using the principle of "last value carried forward". None of the patients excluded from per-protocol analysis had an observation after medication. Therefore an additional intention-to-treat analysis was not performed. Demographic' data and baseline characteristics were analysed by means of Mann-Whitney's U-test and Fisher's exact test. Domain-specific RQLQ  scores visual analog scores, results· of global assessment of therapeutic efficacy, and tolerance ratings performed by patients and investigators were analysed by means of explorative methods based on Mann-Whitney statistics and pertinent. 95% CI. An analysis of homogeneity of efficacy data across study centres was performed by providing an overview of treatment effects by mean scores. Because there was no evidence of interaction between centres and treatment no supportive analysis was done.

    Sample Size Calculation
    At the time the study was designed (1995) there was no sample algorithm available for the test to be used. Thus, an appropriate procedure was used:t-test one-sided with the analog difference, which was a standardized difference of 0.5. When the sample size in each group is 72,a two group 0.05 one-sided t-test will have 91% power to reject the null hypothesis that the test and standard are not équivalent (the difference in means is 0.5 or farther from zero in the same direction) in favor of the alternative hypothesis that the means of the two groups are equivalent, assuming that the expected difference in means is 0.0 and the common standard deviation is 1.0.

    RESULTS
    Demographic and Baseline Characteristics
    A total of 146 patients (82 male, 64 female) recruited from 17 centers (each
    contributing 1-25 cases), including 10 general, 5 ear-nose-throat physicians and 2 internists in private practice, were enrolled in the study. From this population 72 patients were randomly assigned to the homeopathic group and 74 to the cromolyn sodium group. A total of 135 patients (68 in the homeopathic,67 in the cromolyn sodium group) completed the trial according to protocol Seven patients dropped out after visit 2 (2 patients in either group due to end of pollen season; one from the homeopathic and 2 from the cromolyn sodium group due to lack of efficacy/wish of patient/or other reasons).They were included in the analysis of efficacy, whereas 4 other patients could not be included because they dropped out before visit 2 (one of the cromolyn sodium group due to adverse events and 2 from the cromolyn sodium group and one from the homeopathic group due to lack of efficacy/wish of patient/other reasons)(fig.1): Demographic characteristics of the total study population are summarized in table 1. There were no statistically significant differences between the two treatment groups with respect to sex, age, height and weight. The same applies to the overall RQLQ score at visit 1 which averaged 2.37 in the cromolyn sodium and 2.41 in the homeopathic group (but individually reached up to 4.7 and 4.9 respectively, thus indicating that higher baseline scores were disfavoured in this study but not excluded). Comparability can also be assumed for the essential anamnestic parameters (table 2). In only 4 of the enrolled patients hay fever was newly diagnosed; the others had suffered from one or more previous episodes of the disease (mean duration of medical history: 9.3 years in the homeopathic and 7.2 years in the cromolyn sodium group), most of them for 1-6 months during spring and/or summer. In the 51 patients of either group for which they were documented the provoking allergen(s) were tree pollens (mostly hazel, birch; alder, ash), alone or in combination with grass or weed pollens (such as mugwort and rye) without notable group-specific differences. Since the patients lived in the same geographic region it can be concluded that the patients and thus the treatment groups were simultaneously exposed to roughly the same pollen types and concentrations (fig. 2). In both groups the beginning of treatment was similarly distributed to the months of the year (between February and August with an accumulation·in spring). Equivalence considerations can therefore be carried out disregarding environmental and predisposition conditions. An influence of concomitant medication (which was used by 16 patients in the homeopathic
    group and 12 patients in the cromolyn sodium group) on the study results did not become evident. The average compliance with the administration of the two study drugs (93% in the homeopathic group and 98% in the cromolyn sodium group) was comparable.


    Efficacy
    Data from a total of 142 patients (71 homeopathic and 71 cromolyn sodium) were subjected to efficacy analysis. Figure 3 which illustrates the time course of the mean overall RQLQ score from visit 1 to visit 5 reveals a marked reduction of subjective impairment in both treatment groups starting from nearly equal baseline levels. The decrease of the primary parameter was slightly more pronounced in the cromolyn sodium group (from 2.37 to 1.33) than in the homeopathic group (from 2.41 to 1.57). Under both treatments, the effect was most striking during the first week. The alternative hypothesis (therapeutic non-inferiority of homeopathic versus cromolyn sodium treatment) with a=0.05 with the chosen equivalence bound P(X<Y)=0.36 is confirmed The Mann-Whitney statistic for the combined（directional) test of this study was P(X<Y)=0.44, showing the homeopathic group to be slightly inferior. However, the lower bound of the confidence interval was 0.37 which is above the equivalence bound of 0.36. Thus, equivalence (efficacy) of the homeopathic treatment could be proven.

    All RQLQ subscore means showed tine courses Similar to that of the overall score. Mean baseline subscores ranged from 3.34 jo 1.53 and mean final scores from 1.93 to 0.99. The most marked reductions, amounting to 1.2 to 1.6 points, were related to nasal symptoms, practical problems and individual activities (table 3). The results of the visual analog scores were in accordance with the RQLQ scores, indicating that the perceived quality of life increased during the study. Between visit 1 and visit 5, the visual analog scores of the homeopathic group increased 24% (from 55 to 68mm) and those of the cromolyn sodium group increased 29% (from 57 to 74 mm) (Visit 1:U-test P=0.72,P(X<Y)=0.47,95% CI-LB=0.38; Visit 5:U-test P=0.92,P(X<Y)=0.43,95% CI LB=0.35).

    Global assessments of therapeutic efficacy did not markedly differ with respect to treatments or the rating person. The therapeutic efficacy of the homeopathic treatment (vs. the cromolyn sodium treatment) was rated as "excelļent" by 13% (vs. 24%) of the patients and 16% (vs. 18%) of the investigatorş, as "good" by 63% (vs. 55%) and 63%(vs. 66%) respectively as "satisfactory" by 18% (vs. 14%) and 17% (vs. 9%), respectively and as“poor" by 6% (vs. 6%) and.4% (vs. 6%), respectively (patient assessment: U-test P=0.92, P(X<Y)=0.44,95% CI LB=0.37;investigator assessment: U-test P=0.82,P(X<Y)=0.46,95% CI LB=0.39).

    Tolerance
    Under both treatments rhinoscopic assessments of erythema, edema, and dryness of the nasal mucosa remained largely unchanged during visits 2 through 5. In the cromolyn sodium group there was a sustained minor relief of all symptoms whereas the ratings in the homeopathic group, also being consistently slightly better at the beginning than at the end of the observation period, were subjected to some intermediate fluctuation. Similar results occurred relative to patients' assessments of nasal pruritus, sneezing, and sensations of burning and dryness of the nose. All of these symptoms were rated as less intense and less frequent at visit 5 than at visit 2. The differences were small and comparable for both treatments. The tolerance of the homeopathic treatment (vs. the cromolyn sodium treatment) was assessed as "very good" by 25% (vs. 28%) of the patients and 29% (vs. 31%) of the investigators; as "good" by 69% (vs. 61%) and 63% (vs. 58%), respectively; and as“satisfactory/poor” by 4% (vs. 5%) and 7% (vs. 5%), respectively. In general, the vast majority of investigators and patients had no complaints about tolerance (patient
    assessment: U-test P=0.70, P(X<Y)=0.48,95% CI LB=0.41;investigator assessment: U test P=0.63,P(X<Y)=0.48.95% CI LB=0.40).


    Safety
    A total of four adverse events (observed in three patients) reported during the study were rated as "possibly," "probably," or "very probably" related to treatment. All were mild to moderate. Minor intermittent nose bleeding occurred for two days after 30 days of homeopathic treatment. A sensation of burning in the nose, as well as discrete facial exanthema occurred for 8 days after 1 day of homeopathic treatment. A sensation of burning in the nose, which caused the patient to drop out of the study, occurred after 5 days of cromolyn sodium treatment. All adverse events disappeared spontaneously; a premature revelation of the random code was not necessary: All clinically relevant laboratory values
    measured during the study resulted from concomitant.or intervening diseases. Medians of haematology clinical chemistry, urinalysis, and vital signs at visit 1 and visit 5 were consistent with normal values. There was no evidence of adverse systemic action for either the homeopathic or cromolyn sodium treatment.


    DISCUSSION
    Topical cromolyn sodium is a well-established standard therapy for seasonal allergic rhinitis and·conjunctivitis that proved superior to placebo in many clinical trials and has frequently been used as reference (e.g. [14-21]). By this means it was possible to avoid the ethical problems arising from implementation of a placebo treatment in patients suffering from symptoms of considerable intensity. For the present study these problems would have been particularly relevant due to the long duration of 6 weeks. Moreover, to prevent a high dropout rate. in a placebo group and yet to maintain double-blind conditions it would have been necessary to allow non-homeopathic rescue medication (e.g. a topical antihistamine) also to the patients of the homeopathic group; this however would have restricted the validity of the study. results since the interaction of homeopathic and non-homeopathic medication cannot be evaluated. For the same reason the only rescue measure allowed in this trial was a short-term dose increase of the regular compound to which the particular patient had been randomized.

    However, even in the absence of a placebo control the study results strongly suggest that both treatments were in fact effective. About 70-80% of the total mean overall RQLQ score reduction. Occurred within the first two weeks of treatment in both groups. Because most patients were experienced hay fever sufferers who consulted physicians at an early stage of symptom development, it is likely that antigen exposure increased rather than decreased during the initial treatment period. From anamnestic data we know that the majority of patients were sensitive to different antigens being present during different periods so that their hay fever persisted for months. Moreover, only 4 patients dropped out due to end of pollen season (i.e. due to cessation of airborne pollen dissemination). It can therefore be assumed that antigenic exposure was maintained throughout the 6 weeks of treatment.


    In their validation studies Zander et al [9] found a mean overall RQLQ score of 1.0 in a population of asymptomatic hay fever patients investigated during the winter; in a group of symptomatic patients completing the RQLQ during hay fever season they found a score of. 3 0 before and a score of 1.5 after 14 days of anti-allergic treatment. For the present study these results suggest two conclusions. First at the end of both homeopathic and cromolyn sodium treatment the remission·of hay fever symptoms and associated subjective impairment was larġely complete. The final mean RQLQ scores of 1.57 for the homeopathic group and 1.33 for the cromolyn sodium group (which correspond fairly well to the post-treatment result of the validation study) are close to the putative minimum level, which likely could not have been reduced much further considering the persistence of antigen exposure.


    Second, the mean pretreatment overall RQLQ score in the symptomatic groups of the Zander et.al studies.[9] may have been more representative than the mean pre-treatment scores in the present study, in which participation depended on certain restrictions that disfavoured the enrolment of patients with severe allergic reactions. Therefore, the statements about the efficacy of homeopathic and cromolyn sodium therapy may be particularly valid in cases of mild or moderate symptoms of seasonal allergic rhinitis that prevail in the general population.

    Interestingly, the intensity of ocular. symptoms in this study was reduced, according to the pertinent drop in RQLQ score, from 1.87 to 1.26 in the homeopathic group, and from 2.12 to 1.10 in the cromolyn sodium group, although only 6 patients in the homeopathic and 2 in the cromolyn sodium group used eye drops. This ocular relief has also been described in other studies [17,22] involving intranasal cromolyn sodium and antihistamines (and may therefore represent a general indicator of a successful therapy) and was not attributed to a systemic action but to an improved nasal drainage.

    A recent meta-analysis showed that the clinical effects of homeopathy generally are due to more than a placebo effect [23], and in a study using an oral formulation of mixed grass pollens this was demonstrated for the therapy of hay-fever in particular [24]. However, the mode of action of homeopathic treatment is controvérsial. According to one hypothesis, homeopathic drugs act through regulation of gene expression [25]. A different view suggests they act by stimulating an immunological bystander reaction [26,27]. Up to now the effects of homeopathic remedies on the lgE- and mast cell-mediated pathopysiology of allergic rhinitis have not been investigated.

    Homeopathic therapies represent an alternative to conventional methods for
    physicians and patients who seek unconventional treatments. The demand for effective medical alternatives was highlighted by a study in 1990 which estimated that Americansmade 425 million visits to providers of unconventional therapy, compared with 388 million visits to all U.S. primary care physicians [28]. In conclusion; the homeopathic nasal spray proved as effective, safe; and well-tolerated therapy for seasonal allergic rhinitis as the conventional cromolyn sodium nasal spray in this study.

    Tab. 1: Demographic and baseline characteristics of total population by treatment group（SD=standard deviation).

    Tab. 2: Allergy-specific anamnestic data of patients included in efficacy evaluation by treatment group ('mean duration of individual history before enrolment±SD [years], 2 duration unknown, 3 patients could be assigned to more than one category, SD=standard deviation).

    Tab. 3: Means±SD of RQLQ subscores at visit 1 and visit 5 (Mann-Whitney statistic P(X<Y), and pertinent lower 95% confidence bounds in parentheses, SD=standard deviation).

    Fig. 2: Classification of pollen exposure (1=first half of_the month,2=second half of themonth, the data based on the information from the Deutsche Pollenflugwetterdienst and were pooled for the years 1996/97:1=mild,2=moderate,3=severe,4=very severe).

    Fig. 3: Time course of the mean overall RQLQ·score under homeopathic and cromolyn sodium treatment.