Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung cancer.

BACKGROUND: R115777 (tipifarnib, Zarnestra) is a farnesyl transferase inhibitor that blocks the farnesylation of proteins involved in signal transduction pathways critical for cell proliferation and survival. This multicenter phase II study was conducted to determine the efficacy, tolerability and pharmacokinetics of R115777 in patients with relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients who had a partial or complete response to their initial chemotherapy regimen, followed by at least 3 months off treatment before relapse (sensitive relapse) were eligible. R115777 was administered in 3-week cycles at a dose of 400 mg orally twice daily for 14 consecutive days followed by 7 days off treatment. RESULTS: Twenty-two patients were enrolled. The median progression-free survival was 1.4 months and median overall survival was 6.8 months. Non-hematological toxicities were predominantly grade 1-2 and included nausea (64%) and fatigue (60%). Grade 3-4 granulocytopenia and thrombocytopenia occurred in 27% and 23% of patients, respectively. Febrile neutropenia was not observed. Pharmacokinetic studies demonstrated peak plasma concentrations of R115777 2.6-4.5 h after oral dosing and no significant drug accumulation. The trial was terminated because no objective responses were observed in 20 patients evaluable for response. CONCLUSIONS: R115777 showed no significant antitumor activity as a single agent in sensitive-relapse SCLC.

A novel covalent modification of nitrogenase in a cyanobacterium.

In extracts of the unicellular cyanobacterium Gloeothece, the Fe-protein of nitrogenase can be separated by SDS-PAGE into two antigenically identifiable components. Unlike the situation in photosynthetic bacteria such as Rhodospirillum rubrum, these two forms do not arise from covalent modification of the protein by ADP-ribosylation. Rather, the Fe-protein of Gloeothece nitrogenase is subjected to modification by palmitoylation.

Ketoconazole 2% shampoo in the treatment of tinea versicolor: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast. This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions. The topical short-term application of ketoconazole 2% shampoo may provide effective and safe therapy for tinea versicolor. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single application (1 day) versus three daily applications (3 days) of ketoconazole 2% shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor. METHODS: Three hundred twelve patients were included in the primary analyses for this 31-day study. Global evaluation scores were measured on days 10 and 31 with a 5-point scale (1 = healed to 5 = worsening), and a cellophane tape test was done at baseline and days 3, 10, and 31. Efficacy was assessed by clinical response, defined as both a global evaluation score of 1 (healed) and a negative cellophane tape test on day 31. Signs and symptoms of tinea versicolor (scaling, itching, erythema, hypopigmentation, hyperpigmentation) also were evaluated at baseline, day 10, and day 31 with a 4-point scale (0 = absent to 3 = severe). RESULTS: Both regimens of ketoconazole shampoo were significantly (P < .001) more effective than placebo for rate of clinical response, global evaluation scores, and mycologic outcomes (cellophane tape test). The clinical response rates at day 31 were 73%, 69%, and 5% for the 3-day ketoconazole, 1-day ketoconazole, and placebo groups, respectively. The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant. There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events. No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event. CONCLUSION: Ketoconazole 2% shampoo, used as a single application or daily for 3 days, is safe and highly effective in the treatment of tinea versicolor.

Computer use by general practitioners in Scotland.

BACKGROUND: Despite the widespread adoption by general practitioners (GPs) of desktop computers, there has been very little evaluation of the way in which the computer is actually used during consultations and the way in which it affects patient satisfaction. AIM: To ascertain the extent to which the computer is used in the consultation and to investigate the possible relationship between computer use and patient satisfaction. METHOD: Six GPs completed a short questionnaire about the extent to which they use the computer during surgeries. Eighty-four consultations from the surgeries of these GPs were video recorded. Patient satisfaction data on these 84 patients were collected at the time of the surgery using the previously validated Consultation Satisfaction Questionnaire. RESULTS: All six GPs stated that they usually used the computer during consultations. However, video observation revealed that the computer was used in just 51% of surgeries. The proportion of time that the computer was used for varied from 0.03 to 0.4, with a mean value of 0.12. The commonest function for which the computer was used was prescribing. The consultations in which the computer was used (CU) were on average 148 seconds longer than the non-computerized consultations (NCU). There was no difference in patient satisfaction between the two groups. CONCLUSION: Despite this group of GPs having a self-declared interest in the use of computers, the extent to which the computer was used was much lower than expected from the GPs' self-reported use. This may be partly explained by the fact that using the computer takes up valuable time within the consultation and does not appear to contribute to patient satisfaction. If desktop computers are to be used to their full potential in general practice, more work is required to evaluate their impact on the consultation process itself.

Fecal incontinence in children: treatment with percutaneous cecostomy tube placement--a prospective study.

PURPOSE: To evaluate the technique used for and long-term results of percutaneous cecostomy tube placement for the treatment of fecal incontinence in children. MATERIALS AND METHODS: After an initial pilot study in 15 patients, 42 additional patients with fecal incontinence aged 2-20 (mean, 11.5) years and weighing 9.9-109.0 (mean, 39.2) kg underwent percutaneous cecostomy tube placement. Twenty-nine patients had spina bifida, nine had imperforate anus, three had cloacal anomalies, and one had Hirschsprung disease. Mean follow-up was 265 days (range, 8-503 days). RESULTS: Tube placement was successful in all patients. One patient developed local inflammation after accidental early retention-suture removal, which was treated with suture replacement and intravenous antibiotics. Another developed postprocedural ileus, which resolved. Late complications included constipation in one patient (treated with diet alteration), granulation tissue in seven patients (treated with silver nitrate cautery), and accidentally dislodged tubes in three patients (two successfully replaced at home and one replaced at the radiology suite). Vomiting related to the phosphate enema occurred in two patients. Resolution of soiling was achieved in all patients. CONCLUSION: Percutaneous cecostomy and antegrade enemas are very successful in achieving fecal continence and patient independence and acceptability, with minimal early and late complications.

Comparison of sedation regimens for pediatric outpatient CT.

The purpose of this study was to compare the concurrent use of chloral hydrate (CH), intramuscular Nembutal (IMN) and intravenous Nembutal (IVN) for sedation. Data was collected on all pediatric outpatients requiring sedation for CT over a 2.5-year period. During this period, 2178 outpatients required sedation of whom, 1324 (60.8%) received IMN, 710 (32.6%) IVN and 110 (5%) CH. The overall success rate was 97% and was similar in all three groups. IVN however, produced better-quality sedation than IMN or CH. The IVN group received a significantly lower dose of Nembutal than the IMN group (p = 0.001). Patients receiving IVN had a significantly lower induction time (p = 0.0001) and total examination time (p = 0.001) than IMN or CH. There was an increased occurrence of desaturation in patients sedated with IVN, especially in those with airway obstruction. IVN sedation permits faster, more efficient and better-quality sedation for outpatient CT scanning than IMN or CH in patients requiring intravenous contrast but may not be appropriate for departments that perform relatively few sedations or lack proper resuscitation facilities.

Hydrometrocolpos and polydactyly.

Two cases of hydrometrocolpos and polydactyly in female infants with persistent urogenital sinus are reported. The importance of considering hydrometrocolpos as the cause of an abdominal mass in female infants with polydactyly is stressed. Cytologic examination of the vaginal fluid may help in early diagnosis.