Biomedical subjects

R W Gorter

Publications and source records attributed to R W Gorter.

12 recordsLinked to original sources

PubMed2002

Safety, tolerability, and efficacy of orally administered cannabinoids in MS.

The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression.

Administration, Oral↗

PubMed2000

Prospective cohort trial of Euphrasia single-dose eye drops in conjunctivitis.

INTRODUCTION: Eye drops made from Euphrasia rostkoviana Hayne have been used in anthroposophical medicine for more than 70 years for the structuring of the fluid organism in the eye, especially in inflammatory and catarrhal conjunctivitis. The aim of this prospective cohort trial was to describe the efficacy and tolerability of these eye drops in a community-based setting. To evaluate these questions, prospective cohort studies are the best method. This enables the investigator to attain real insights as to which treatment administered related to specific results in a specific group of patients. DESIGN: Prospective, open label, one-armed, multicentered, multinational cohort trial. SETTING: The trial was carried out in the clinics of 12 experienced anthroposophical general practitioners and ophthalmologists in Germany and Switzerland. PATIENTS: Patients with inflammatory or catarrhal conjunctivitis, treated with Euphrasia single-dose eye drops were included in the trial. INTERVENTION: One drop of Euphrasia single-dose eye drops 1-5 times a day was prescribed. The prescription was determined solely by medical therapeutic needs. OUTCOME MEASURES: Efficacy variables were: redness, swelling, secretion, burning of the conjunctiva, and foreign body sensation. Tolerability variables were: conjunctival reddening, burning of the conjunctiva, foreign body sensation, and veiled vision. All symptoms were given for the right or left eye separately, with degree of severity in relation to baseline after approximately 7 days (+/-3 days; first follow-up examination) and after approximately 14 days (+/-3 days; second follow-up examination). If, after the first follow-up, all symptoms had disappeared, no second follow-up was done. RESULTS: Sixty-five (65) patients fulfilled the inclusion criteria for the protocol evaluation. A complete recovery was seen in 53 patients (81.5%) and a clear improvement in 11 patients (17.0%). A slight worsening could only be determined in 1 patient in the second week of treatment (1.5%). No serious adverse events were observed during the entire trial. The efficacy and tolerability were evaluated by the patients and doctors as "good" to "very good" in more than 85%. CONCLUSION: Euphrasia single-dose eye drops can effectively and safely be used for various conjunctival conditions by general practitioners and ophthalmologists. A dosage of one drop three times a day seems to be the general prescribed dosage.

Cohort Studies↗

PubMed1999

Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks.

Subcutaneous injections of fermented and unfermented aqueous extracts of Viscum album L. result in a local inflammatory reaction at the injection site. In this trial, the symptoms associated with this local reaction were investigated. Furthermore the occurrence of local reactions was tried to correlate with an increase in CD3/25- and CD8/38-positive lymphocyte counts, with eosinophilic granulocyte numbers, and with the formation of mistletoe lectin antibodies. Included in the trial were 30 HIV-antibody-positive patients and 17 healthy non-smokers, aged 24-51 years. The CD4 cell count in the HIV-negative subjects was > 800/microliter, compared with 200-600/microliter in the HIV-positive patients. All study participants had a Karnofsky score > or = 70. The trial subjects were observed over a period of 18 weeks. With escalation of the dose of a fermented and unfermented extract of Viscum album L. (Iscador Qu Spezial and Viscum album QuFrF), there was an increase in local reactions. Erythema at the injection site was the most frequently reported symptom. Between the doses and the symptoms induration, swelling and pruritus were marked correlations. Effects of the application of mistletoe extracts on the immune system were demonstrated by an increase in CD3/25-positive lymphocyte counts and antibodies against mistletoe-lectins. There were no changes in eosinophilic granulocytes or CD8/38-positive lymphocyte populations. For evaluation of the therapeutic applications of mistletoe extracts in HIV-positive patients it is advisable to assess primarily activation of CD3-positive lymphocytes and the patient response on the basis of the local reaction. The local inflammatory reaction at the injection site is desirable and well tolerated if the reaction is smaller than 5 cm in diameter.

Adjuvants, Immunologic↗

PubMed1999

Toxicity of a standardized mistletoe extract in immunocompromised and healthy individuals.

Iscador is being used by many patients as unconventional anticancer and immunomodulating therapy. To determine the toxicity profile and biochemical effects of Iscador Qu Spezial (Weleda AG Schwäbisch Gmünd, Germany) in human immunodeficiency virus (HIV)-positive patients and healthy controls, we performed a phase I/II study. Escalating doses of Iscador Qu Spezial, standardized for its lectin and viscotoxin content, were administered to 16 HIV-positive patients and 8 healthy subjects during a period of 6 to 8 months. Iscador Qu Spezial preparations were administered twice per week subcutaneously in increasing doses (ie, 0.01 mg, 0.1 mg, 1.0 mg, 2.0 mg, 5.0 mg, and 0.1 mg/kg for 2-6 weeks per dose). Drug-related adverse effects were flulike symptoms, gingivitis, fever, local erythema, and eosinophilia. These side effects were never severe. The incidence of systemic adverse events was highest in HIV-positive patients. Furthermore, increased urea levels and slightly decreased total protein caused by a minor decrease in albumin were observed. None of the HIV-positive patients progressed in disease stage. Iscador Qu Spezial can be administered safely to immunocompromised patients.

Adjuvants, Immunologic↗

PubMed1999

Cancer cachexia and cannabinoids.

Anorexia and cachexia are diagnosed in more than two-thirds of all cancer patients with advanced disease, and are independent risk factors for morbidity and mortality. Anorexia, nausea and vomiting often are described as more significant inhibiting factors for quality of life of cancer patients than even intense pain. In 1986, delta-9-tetrahydrocannabinol (THC), the main effective constituent of cannabis, was licensed as an anti-emetic drug in cancer patients receiving chemotherapy. In addition, in clinical studies THC has shown significant stimulation of appetite and increase of body weight in HIV-positive and cancer patients. The appetite-stimulating effect of cannabis itself has also been well documented in many anecdotal cases. There are strong indications that cannabis is better tolerated than THC alone, because cannabis contains several additional cannabinoids, like cannabidiol (CBD), which antagonize the psychotropic actions of THC, but do not inhibit the appetite-stimulating effect. Therefore, we intend to compare the therapeutic effects of whole-plant extracts of cannabis to those of THC (dronabinol) alone in controlled studies.

Appetite Stimulants↗

PubMed1999

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area].

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications.

Adolescent↗

PubMed1999

Tolerability of an extract of European mistletoe among immunocompromised and healthy individuals.

CONTEXT: European mistletoe (Viscum album L) has been used parenterally for more than 80 years as an anticancer medication with significant immunomodulating action. Since 1984, clinical experience with a Viscum album extract (Viscum album Quercus Frischsaft [Qu FrF]) among HIV-positive patients has suggested that it inhibits HIV disease progression. OBJECTIVE: To determine the toxicity profile and biochemical effects of a Viscum album extract. DESIGN: A dose-escalating phase I/II study. PATIENTS: 32 HIV-positive and 9 healthy participants. INTERVENTION: Standardized for its lectin and viscotoxin content, the extract was administered subcutaneously twice weekly in gradually increasing doses for 2 to 17 weeks per dose increase. Doses of 0.01 mg to 10.0 mg were administered. MAIN OUTCOME MEASURES: Adverse events, hematology, and biochemistry. RESULTS: No severe side effects were found. During gradual dose escalation, more adverse events occurred at the lower dose range. The hazard rate of systemic adverse events was highest among HIV-positive patients. Drug-related adverse events were flu-like symptoms and transient exacerbations of gingivitis, fever, and eosinophilia. An increase of serum urea nitrogen and serum creatinine levels occurred, as did a slight decrease in total protein caused by a minor fall in albumin concentrations. Dose dependence was apparent for inflammation and fever, which may or may not have been side effects of the preparation. CONCLUSIONS: Viscum album Qu FrF can be administered safely to HIV-positive patients. It induces immunomodulation in HIV-positive and healthy individuals and may inhibit the progression of HIV disease.

Adolescent↗

PubMed1998

Subcutaneous infiltrates induced by injection of mistletoe extracts (Iscador).

Iscador, an aqueous extract of Viscum album L., has been widely used as an anti-cancer drug for several decades. Mistletoe lectins have the capacity to activate nonspecific defense mechanisms, and lectin-carbohydrate interactions may be involved in clinically applicable immunomodulation. During treatment with whole-plant mistletoe extract, an inflammatory reaction usually occurs at the site of the injection, early in therapy. These injection sites were examined histologically. Seven subjects received three subcutaneous injections of Iscador QuFrF or Iscador Qu Spezial (twice 0.1 mg and once 2.5 mg) during 9 days. In all subjects, examination of skin biopsies showed a normal epidermis. The dermal and subcutaneous regions contained a dense perivascular lymphocyte infiltrate and increased monocytes. We could not document any increase of plasma cells, eosinophils, mast cells, neutrophils, or granulocytes, as would be the case for a granulomatous infiltrate. In the blood, we observed a significant increase in neutrophils and monocytes 24 hours after administration of 2.5 mg of Iscador.

Adult↗

PubMed1998

No evidence of IFN-gamma increase in the serum of HIV-positive and healthy subjects after subcutaneous injection of a non-fermented viscum album L. extract.

Iscador, an aqueous extract of Viscum album L., has been used for more than 80 years as an anticancer drug. Due to its immunomodulatory potential, since the onset of the AIDS epidemic it has also been applied in the treatment of HIV-positive and AIDS patients in the form of the preparation V. album QuFrF (VaQuFrF; Labor Hiscia, Arlesheim, Switzerland). In in vitro investigations, incubation of peripheral blood mononuclear cells with V. album L. extracts resulted in stimulation of lymphocyte activity with increased gene expression and release of various cytokines and also of interferon gamma (IFN-gamma). In the latent phase, HIV positives exhibit only slightly elevated IFN-gamma concentrations in serum in comparison with HIV negatives, but in the acute phase of AIDS, there is an increase in levels of IFN-gamma. As the assay of cytokine levels in serum is a simple method of measuring immune system reactions, the aim of this trial was to determine whether increases in serum IFN-gamma levels in HIV positives and HIV negatives can be detected using this method after repeated injections of VaQuFrF. Five healthy subjects and 13 HIV-positive patients were investigated. IFN-gamma concentrations in serum were assayed using an ELISA test kit (ELISA test; ENDOGEN, Cambridge, Mass., USA). No drug-related elevation of serum IFN-gamma was observed at any time point during the trial. It can thus be concluded that this method is not suitable for direct investigation of the immunomodulatory effects of VaQuFrF in vivo.

Adjuvants, Immunologic↗

PubMed1998

Decrease of activated lymphocytes four and nine hours after a subcutaneous injection of a Viscum album L. extract in healthy volunteers.

The immunomodulatory substance, VaQuFrF (an aqueous extract of Viscum album L. of the oak tree) is used as an adjuvant and as monotherapy in the treatment of cancer and AIDS. After subcutaneous injection, there is a local inflammatory reaction at the injection site and systemic elevation of activated lymphocytes. The immunomodulatory effect of VaQuFrF in the first 24 h after subcutaneous injection on blood leukocyte and lymphocyte subpopulation was investigated. Because a significant natural circadian variation of these cellular parameters exist, the influence was studied in regard to this. In two groups of healthy volunteers, one group receiving VaQuFrF, the following parameters were measured every 2-3 h over a period of 24 h: leukocytes, band form, segmented and eosinophilic granulocytes, monocytes, total lymphocytes and CD4-, CD8-, CD3/25- and CD8/38-positive lymphocytes in count and percentage. In regard to the natural circadian variation 24 h after injection of VaQuFrF, a statistically significant fall in the absolute numbers and percentage of CD3/ 25- and CD8/38-positive lymphocytes was observed. Also, monocytes in percent and absolute numbers show a transient fall 6-9 h, lymphocytes only in absolute and CD4-positive lymphocytes only in percentage 2 h after injection. The results demonstrate that there is increased extravasation of (activated) lymphocytes and monocytes after subcutaneous injection of 1 mg VaQuFrF.

Adjuvants, Immunologic↗

PubMed1992

Differences in laboratory values in HIV infection by sex, race, and risk group.

OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. DESIGN: Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. METHODS: Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. RESULTS: HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.

Adult↗

PubMed1991

Recent clinical experience with dronabinol.

Dronabinol, delta-9-tetrahydrocannabinol in sesame oil, has been used for several years as an antiemetic for patients receiving cancer chemotherapy. In combination studies with prochlorperazine, enhancement of efficacy, as measured by duration of episodes of nausea and vomiting and by severity of nausea, has been found. The incidence of psychotropic effects from dronabinol appears to be decreased by concomitant administration of prochlorperazine. In open pilot studies, dronabinol caused weight gain in seven of ten patients with symptomatic HIV infection. In both HIV and cancer patients, dronabinol improved appetite at a dose which was well tolerated for chronic administration.

Antineoplastic Agents↗