Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study.

OBJECTIVE: To assess the safety and efficacy of a 0.005% mixture of solasodine glycosides (Zycure) in the treatment of basal cell carcinoma. Design Double-blind, randomized, and vehicle-controlled, parallel group study. SETTING: Ten centers in the United Kingdom. Participants Male, n = 50; female, n = 44; age range, 32-95 years (Table 1). INTERVENTION: Ninety-four patients were randomized on a 2 : 1 ratio (n = 62, Zycure; n = 32, vehicle). Histologically confirmed lesions were treated double blinded, twice daily under occlusion with Zycure or vehicle for 8 weeks. Patients were reviewed fortnightly for adverse effects and overall response. Successfully treated patients were followed up at six-month intervals for a year. MAIN OUTCOME MEASURES: The primary efficacy endpoint was histologically confirmed clearance of the basal cell carcinoma (2-mm punch biopsy) at the end of 8-week treatment. RESULTS: Efficacy (intention-to-treat population) at 8 weeks was 66% (41/62) in the Zycure group, compared to 25% (8/32) in the vehicle group (P < 0.001; Cochran-Mantel-Haenszel test). Ninety percent (37/41) of the Zycure group completed follow-up at six-month intervals for 1 year, of whom 78% (29/37) had no recurrence. There were no major treatment-related adverse effects, although 10 patients in Zycure group did not complete the treatment protocol for various reasons. CONCLUSION: We conclude that the solasodine glycoside cream Zycure is a safe therapy for basal cell carcinoma, with a cure rate of 66% at 8 weeks and 78% at 1 year follow-up.

Nonoperative treatments for sciatica: a pilot study for a randomized clinical trial.

OBJECTIVES: To assess the feasibility of patient recruitment, the ability of patients and clinicians to comply with study protocols, and the use of data collection instruments to collect cost-effectiveness data, and to obtain variability estimates for sample-size calculations for a full-scale trial. STUDY DESIGN: Prospective, observer-blinded, pilot randomized clinical trial. SETTING: Primary contact chiropractic and medical clinics. PATIENTS: Ages 20 to 65 years, with low back-related radiating leg pain (sciatica). OUTCOME MEASURES: Self-report questionnaires were administered at baseline and 3 and 12 weeks after randomization. The measures included leg and back pain severity, frequency and bothersomeness of symptoms, leg/back disability, medication use, global improvement, satisfaction, and health care utilization. INTERVENTIONS: Medical care, chiropractic care, and epidural steroid injections. RESULTS: A total of 706 persons were screened by phone to determine initial eligibility. Of these, over 90% of those persons contacted did not meet the entrance criteria. The most common reason for disqualification was that the duration of the complaint was longer than 3 months. Twenty patients were randomized into the study. All 3 groups showed substantial improvements in the main patient-rated outcomes at the end of the 12-week intervention phase. For leg pain, back pain, frequency and bothersomeness of leg symptoms, and Roland-Morris disability score, the percent improvement varied from 50% to 84%, and the corresponding effect sizes ranged from 0.8 to 2.2. Bothersomeness of leg symptoms was the most responsive outcome associated with the largest magnitude of effect size. All within-group changes from baseline were statistically significant (P <.01). No between-group comparisons were planned or performed because of the insufficient sample size and high risk of committing type I and type II errors. CONCLUSIONS: Pilot studies such as these are important for the determination of the feasibility of conducting costly, larger scale trials. Recruitment for a full-scale study of sciatica of 2 to 12 weeks duration is not feasible, given the methods used in this pilot study. Our results do indicate, however, that there are substantial numbers of patients with sciatica more chronic in nature who would be interested in participating in a similar study. In addition, collaboration with a local health maintenance organization would likely facilitate clinician referrals and optimize the recruitment process. Patient and provider compliance was high in the pilot study, which indicates that most study protocols are feasible. Additionally, we were able to collect complete outcomes data, including those regarding health care use. A suggested modification by investigators and outside consultants has resulted in the replacement of the medication group with a minimal intervention control group (ie, self-care advice). As a result, a second pilot study of patients with sciatica of more than 4 weeks duration has been planned before a full-scale trial is attempted.

Spine fusion for discogenic low back pain: outcomes in patients treated with or without pulsed electromagnetic field stimulation.

Sixty-one randomly selected patients who underwent lumbar fusion surgeries for discogenic low back pain between 1987 and 1994 were retrospectively studied. All patients had failed to respond to preoperative conservative treatments. Forty-two patients received adjunctive therapy with pulsed electromagnetic field (PEMF) stimulation, and 19 patients received no electrical stimulation of any kind. Average follow-up time was 15.6 months postoperatively. Fusion succeeded in 97.6% of the PEMF group and in 52.6% of the unstimulated group (P < .001). The observed agreement between clinical and radiographic outcome was 75%. The use of PEMF stimulation enhances bony bridging in lumbar spinal fusions. Successful fusion underlies a good clinical outcome in patients with discogenic low back pain.

Optimising the use of tazarotene in clinical practice: consensus statement from the European advisory panel for tazarotene (Zorac TM).

BACKGROUND: This paper reports the proceedings of the European Advisory Panel Meeting for tazarotene (Zoractrade mark), which took place in Cologne on May 7, 1998. AIM: The aim of this meeting was to discuss recommendations for the use of tazarotene based on the clinical data available and on the clinical experience of the Advisory Panel members, and to identify future research needs. RECOMMENDATIONS: Based on currently available data, tazarotene can be used for the treatment of chronic, stable, plaque-type psoriasis, on the trunk or limbs covering up to 20% of the body surface area. In clinical trials, patients generally experienced a clinical response within 4 weeks of starting tazarotene treatment, and improvement was maintained for up to 12 weeks after stopping therapy. Results from published and not yet published clinical trials show that the efficacy and tolerability of tazarotene can be enhanced by the addition of topical corticosteroids to the treatment regimen and that, when used in combination with broad-band UVB phototherapy, tazarotene reduces the amount of UV light required to treat plaques. Tazarotene gel is available in two concentrations, 0.05 and 0.1%. The Advisory Panel recommends that the choice of concentration should be based on factors such as the irritability of the patient's skin and the thickness of plaques. Irritation can be managed by reducing the concentration or frequency of application, or by adding a topical corticosteroid to therapy. Tazarotene shows promise as a treatment for psoriasis in special localisations, such as the scalp, face and skin folds, although clinical studies are required.

The prevalence of common skin conditions in Australian school students: 2. Atopic dermatitis.

The prevalence of atopic dermatitis (AD) was recorded following examination by dermatologists and dermatology registrars of a random sample of 2491 school students throughout the State of Victoria, Australia. The overall prevalence, based on clinical examination, was 16.3% (95% confidence interval, CI 14.1-18.5), being higher in girls (17.7%; 95% CI 15.0-20.4) than boys (14.8%; 95% CI 11.8-17.8). Using the U.K. Working Party Diagnostic Criteria for AD reduced the prevalence to 10.8% (95% CI 9.3-12.3) with the prevalence in girls 12.3% (95% CI 10.1-14.4) and in boys 9.2% (95% CI 7.1-11.4). The prevalence was highest in 4-6 year olds (18.7% on clinical examination, 11.5% using the U.K. Working Party Criteria), decreasing with increasing age to 11.6% on clinical examination (8. 6% on U.K. Working Party Criteria) among 16-18 year olds. Most of those with AD were classified as having mild disease (54.1%), with 32.1% classified as having minimal and 13.8% as having moderate to severe disease. Over 80% of those who reported on the questionnaire that they had dermatitis that was then confirmed on examination had been using one or more products to treat it. Nearly 90% of these products were classified as efficacious, with medical practitioners being the major source of advice for their use (77%). Pharmacists (8%), family/friends (6%) and others (9%), including beauticians and naturopaths, made up the remainder of the persons from whom those affected had sought advice about their treatment. These data, the first community-based prevalence data on AD published from Australia, confirm that the condition is common among those of school age. There is a need for AD to be included among those conditions that are discussed in health education lessons in schools.

Lesion size following Gamma Knife treatment for functional disorders.

In this study we investigated the reproducibility and consistency of the size of radiosurgical lesions produced for functional disorders. The T1 gadolinium-enhanced magnetic resonance (MR) images of 56 patients treated for parkinsonism, pain, or other functional diseases were used to measure 140 lesion sizes at various times after radiosurgical treatment (1-26 months, mean: 11.3 months). Only the 4-mm collimator was used to create the lesions. The maximum dose ranged from 110 to 180 Gy (mean: 145 Gy). In 42 cases (78%), one isocenter was used to create the lesion. Thirteen lesions (20%) were created with two isocenters and in 1 case, three isocenters were used. Lesions were detectable on MR images as early as 30 days after treatment. The maximum lesion volume was reached after 6-12 months and ranged from nondetectable to more than 4,000 mm3. Larger lesion volumes were strongly associated with the use of more than one isocenter. In addition, maximum doses of 160 Gy or more increased the likelihood of producing lesions larger than expected. It is therefore concluded that the use of the Gamma Knife for the treatment of functional disorders is safest when single-isocenter shots with the 4-mm collimator and a maximum dose of less than 160 Gy are used.

Postoperative blood salvage in total knee arthroplasty using the Solcotrans autotransfusion system.

One hundred forty-four patients who underwent primary total knee arthroplasty were examined in a prospective controlled study to determine the efficacy and safety of a postoperative wound drainage autotransfusion system (Solcotrans, Smith & Nephew Richards, Memphis, TN). The patients were divided into two groups: control group 1 comprised 88 (61%) patients who either received a Hemovac disposable drainage system (63 patients) or the Solcotrans system and had inadequate drainage for autotransfusion (25 patients). Experimental group 2 comprised 56 (39%) patients who received a Solcotrans drainage system and were autotransfused. The Solcotrans proved itself safe. No sepsis, transfusion reactions, or coagulopathies were associated with autotransfusion, which averaged 524 mL. There were no significant differences between groups 1 and 2 when comparing preoperative and postoperative hemoglobins and hematocrits. The Solcotrans system did not lower homologous blood requirements. Only 1.6% (2 patients) of all patients who autodonated at least 2 units of autologous blood (122 patients) were in need of a homologous blood transfusion in the postoperative period. Thus, although safe, the Solcotrans system was not proven effective in the management of primary total knee arthroplasty patients.

Reduction of solar keratoses by regular sunscreen use.

BACKGROUND: The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous-cell carcinoma of the skin. METHODS: We conducted a randomized, controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer (September 1991 to March 1992). The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head, neck, forearms, and hands. RESULTS: The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group (difference, 1.53; 95 percent confidence interval, 0.81 to 2.25). The sunscreen group had fewer new lesions (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71) and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80) than the base-cream group. There was a dose-response relation: the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones. CONCLUSIONS: Regular use of sunscreens prevents the development of solar keratoses and, by implication, possibly reduces the risk of skin cancer in the long-term.

The effect of 3 mouthrinses on plaque and gingivitis development.

The aim of this study was to evaluate the effect of 3 mouthrinses, Listerine Antiseptic (thymol), Peridex (chlorhexidine), Perimed (povidone iodine and hydrogen peroxide), and a placebo (water) on the development of dental plaque and gingivitis, when used as the only oral hygiene procedure for 14 days. 71 subjects were entered into a randomized, double-blind study. At the baseline examination, papillary bleeding score (PBS), and plaque index (PI) were registered, after which subjects received supragingival prophylaxis and were assigned to 1 of 4 study cells. Subjects were asked to refrain from all oral hygiene procedures except for the supervised 14-day 2 x daily rinsing with the assigned preparation. At day 14, the same clinical parameters were again registered. Statistical analysis was performed by a one-way analysis of variance (ANOVA) to compare the 4 groups, followed by Duncan's multiple range test to determine specific group differences. At baseline, average PBS and PI scores were similar for all 4 groups. After 14 days, the average PBS for Peridex and Perimed was significantly lower than for Listerine Antiseptic and water. The frequency of interdental units with a PBS greater than 2 was significantly lower for Peridex and Perimed than for Listerine Antiseptic and water. We concluded that both Peridex and Perimed were effective in reducing plaque and gingivitis when used as a 2 x daily mouthrinse by subjects refraining from other oral hygiene procedures. In vitro, a synergistic effect was assumed when inhibition was achieved with Perimed at the same or greater dilution than was achieved with povidone-iodine alone.

Effect of psyllium hydrophilic mucilloid on serum cholesterol in the elderly.

The effect of psyllium hydrophilic mucilloid (PHM) when used as a laxative and/or stool softener on serum cholesterol concentrations was examined in 176 ambulatory elderly participants attending a health screening program. The change in one-year serum cholesterol concentration in subjects using PHM was compared with the change in cholesterol in 741 participants who did not report the use of PHM. Serum cholesterol concentration decreased by 0.073 mmol/liter (2.82 mg/dl) in the treatment group compared with a decrease of 0.036 mmol/liter (1.39 mg/dl) in the control group. After adjusting for confounding factors, excluding psyllium dose, by using a multiple regression model there was no significant difference in the change in serum cholesterol concentration (P = 0.935). PHM dosage information was available for 158 participants. After adjusting for baseline serum cholesterol and confounding factors using multiple regression analysis, it was found that the dose of PHM administered was significantly correlated with the change in serum cholesterol (P = 0.0120). For every 1-g increase in daily PHM dose there was a 0.022 mmol/liter (0.84 mg/dl) decrease in serum cholesterol concentration.

The effects of an abrasive agent on normal skin and on photoaged skin in comparison with topical tretinoin.

Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol fine and Brasivol medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride-induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol medium) was compared with 0.05% tretinoin cream (Retin A) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8-week period. Cutaneous blood flow measured by the laser-Doppler flowmeter was found to be significantly increased in the abrasive-treated sites, but there was only a non-significant trend to increased blood flow in the tretinoin-treated sites. Measurements of skin thickness using pulsed A-scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8-week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive-treated sites only. Measurements of epidermal thickness and of [3H]-thymidine autoradiographic labelling indices showed greater increases in the abrasive-treated sites than in tretinoin-treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a 'repair zone' were found in any of the post-treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation.

Treatment of abdominal nerve entrapment syndrome using a nerve stimulator.

Seventy-six patients treated at York Pain Relief Clinic for Abdominal Nerve Entrapment Syndrome (ANES) between 1982 and 1986, using aqueous phenol and nerve stimulator control are reviewed. A questionnaire was sent to all the patients who had been discharged from the clinic to try to confirm that the initial improvements had been maintained and 60 patients replied. Group A (n = 44) had been diagnosed with confidence; 95% had gained complete or partial relief of symptoms. Group B (n = 32) had other symptoms making the diagnosis less certain; 50% gained some relief. Clinical presentation of ANES and the method of treatment are described.

Drug use in an ambulatory elderly population: a five-year update.

Drug usage was studied in an ambulatory elderly population in Dunedin, Florida. Prescription and nonprescription drug use in these 2834 participants was compared with use during a period five years earlier. The average number of medications increased from 3.2 in 1978-80 to 3.7 in 1983-85. The most commonly prescribed medications in this population were hydrochlorothiazide-triamterene (13.5 percent), digoxin (9.6 percent), and hydrochlorothiazide (8.4 percent). There was a large increase in the use of nutritional supplements in the past five years, with 18.0 percent of these subjects reporting the use of vitamin E and 15.7 percent taking vitamin C. The general philosophy in geriatrics is to use the fewest drugs possible; however, it appears that the elderly are, in fact, receiving an increasing number of medications.

Effect of antirheumatic agents on the mitogen response of arthritic rat spleen cells.

Splenic lymphoid cells from rats with adjuvant induced polyarthritis show a diminished response to the T-cell mitogens Con A and PHA. This report describes the in vitro effects of various antirheumatic agents on the mitogen induced proliferative response of normal (NSC) and arthritic (ASC) rat spleen cells. Indomethacin enhanced only the arthritic responses. Other PG synthesis inhibitors such as ibuprofen and naproxen enhanced the arthritic as well as the normal spleen cell proliferative responses. Gold sodium thiomalate augmented arthritic but not normal blastogenesis. Penicillamine significantly enhanced only the Con A response of arthritic cells at 10(7)M. Levamisole produced a significant increase in the PHA response of arthritic cells and the Con A NSC response. Chloroquine diphosphate enhanced the Con A response of normal cells at 10(-5)M and 10(-6)M; both chloroquine and tilorone suppressed blastogenesis of arthritic spleen cells at 10(-4)M and 10(-5)M. When classifying antirheumatic agents as stimulator or suppressors of immune function, one must account for their effects on arthritic as well as normal lymphoid cells at the predicted pharmacologic plasma levels.

Acute skin toxicity reactions in man--tests and mechanisms.

There is increasing concern to avoid toxicity reactions from materials that come into contact with the skin. In this paper the mechanisms underlying the commonest type of cutaneous toxicity, i.e. the dermatitis reaction, are discussed. The various tests that may be used to predict human cutaneous toxicity are reviewed, with emphasis on in vivo human toxicity tests. It is concluded that preliminary testing of potentially toxic materials should be conducted in vitro or, until such tests are available, in small mammals, but that definitive tests of finished products should be performed in vivo in man.

Diuretic use in an ambulatory elderly population.

The nature and extent of diuretic use and the effect of diuretics on clinical laboratory values were studied in a retirement community. Study participants completed health questionnaires and provided information on all prescription and nonprescription medications regularly used. Subjects using diuretics were categorized according to product(s) used; a control group used no diuretics. Results for diuretic users who used potassium supplements were analyzed separately. Data were collected on 2009 women and 1183 men over 65 years old. At least one diuretic drug was used by 40.2% of the women and 29.5% of the men. In most cases, the diuretic was used daily (81.1%) and had been used for longer than two years (72.5%). Approximately one third of the subjects had hypertension. Serum potassium values for users of chlorthalidone and thiazide diuretics showed the greatest difference from the control group, while users of the combination of hydrochlorothiazide and spironolactone showed the greatest difference in serum sodium concentrations. Particularly in furosemide users, uric acid, BUN, and creatinine concentrations were significantly different from control. When serum potassium values of subjects using both diuretics and potassium supplements were analyzed, values were lower in participants using supplements. In many cases, significantly different laboratory values were still within normal limits. Long-term diuretic use in this ambulatory elderly population was high and was associated with numerous alterations in biochemical values.

Use of nutritional supplements in an ambulatory elderly population.

The use of nutritional supplements by 3,192 ambulatory elderly participants in a health screening program is described. The 2,009 women used vitamin (45.5 per cent) and mineral (22.4 per cent) products with significantly greater frequencies than did the 1,183 men (34.0 per cent and 15.0 per cent, respectively); chi-square, P less than 0.01. The most commonly used vitamin products were multiple vitamins, multiple vitamins with minerals, vitamin E, and vitamin C; for minerals, the ranking was potassium chloride, calcium salts, and ferrous sulfate. Eighty-two participants (2.5 per cent) reported the use of four or more supplements. Many older Americans are spending a great deal of money for nutritional supplements, whereas it would seem that the money could be better spent to improve the quality of their diet.