Risperidone treatment of outpatients with schizophrenia: no evidence of sex differences in treatment response.

OBJECTIVE: Given the renewed interest in the role of sex differences in schizophrenia, we undertook a post hoc analysis to determine whether sex differences in treatment response were present among outpatients with schizophrenia who received risperidone in an 8-week, open-label, Phase IV clinical study. METHOD: We evaluated 330 adult patients (232 men, 98 women) with a DSM-III-R diagnosis of schizophrenia for safety and 292 (206 men, 86 women) for efficacy. Antipsychotic and antiparkinsonian medications were discontinued at study entry. Treatment with risperidone was initiated at a dosage of 2 mg daily, increased to the target dosage of 6 mg daily by day 3, and maintained at 6 mg daily until day 14. The dosage was then maintained at 6 mg daily, increased or decreased by 2 mg daily each week, based on the patient's response. Risperidone treatment was given for 8 weeks; the permitted dosage range was 4 mg to 10 mg daily. RESULTS: Both male and female participants responded well to risperidone treatment; by the final assessment day, they had experienced decreases from baseline in their total Positive and Negative Syndrome Scale (PANSS) scores of 41.0% and 36.5%, respectively. Most male (77%) and female (78%) participants were considered to be PANSS responders: risperidone was effective against both the positive and negative symptoms of schizophrenia. Both sexes showed improvements over baseline in the incidence and severity of parkinsonism, dystonia, and dyskinesia. No significant (P > 0.05) sex differences in treatment response were observed for any of the efficacy outcomes or in the incidence and severity of extrapyramidal symptoms (EPS). CONCLUSIONS: In this population of outpatients with chronic schizophrenia, both men and women responded well to flexible doses of risperidone. No significant sex differences were evident either in treatment response or in neurological side effects. The absence of sex differences in response to risperidone treatment may obviate the need for a sex-based differential dosing in schizophrenia management.

Effects of washout and dose-escalation periods on the efficacy, safety, and tolerability of galantamine in patients previously treated with donepezil: ongoing clinical trials.

With the increasing number of acetylcholinesterase inhibitors (AChEIs) being marketed for the treatment of Alzheimer's disease (AD), physicians will need protocols for discontinuing one AChEI and initiating another ("switching"). Three clinical trials have been designed to provide data that will assist in the determination of the optimal conditions for switching patients from donepezil (the most widely prescribed AChEI) to galantamine (the most recently approved AChEI). The main objective of these studies is to investigate the effects of different washout periods (0 to 7 days) and dose-escalation schedules (fixed, fast vs slow) on the efficacy, safety, and tolerability of galantamine in patients with AD who were previously taking donepezil. The duration of the trials ranges from 12 to 52 weeks, and the last trial is expected to end in May 2002. No conclusions can yet be drawn from these ongoing trials, but the results should be helpful in establishing guidelines for physicians to use when switching patients with AD from donepezil to galantamine.

Potential of Loperamide Oxide in the Reduction of Ileostomy and Colostomy Output.

The effects of a single oral dose of loperamide oxide on stoma output were evaluated in an open trial that included 22 patients - 4 with a colostomy and 18 with an ileostomy, in whom daily stoma output was usually more than 500g. Antidiarrhoeal therapy was stopped from days 2 to 7, and from days 5 to 8 a standardised high-fibre diet was given. Stoma effluent was collected for 24 hours on day 7. On day 8, patients took one dose of loperamide oxide 6mg. In 20 of the 22 patients, stoma output was reduced by 13 to 75% after administration of loperamide oxide. The mean output was reduced by 45% (p = 0.0001). There were no adverse experiences associated with administration of loperamide oxide. The majority of drug recovered in stoma effluent was loperamide, suggesting extensive conversion of loperamide oxide to loperamide. These preliminary findings suggest that a single 6mg dose of loperamide oxide is effective in reducing stoma output in patients with an ileostomy or colostomy.

Chronic beta-blockade does not influence muscle power output during high-intensity exercise of short-duration.

Patients receiving beta-receptor antagonists for the treatment of hypertension frequently complain of impaired exercise tolerance. To determine whether these medications impair skeletal muscle contractile function, we measured isokinetic muscle function in ten healthy male cyclists receiving nebivolol (N), atenolol (A), propranolol (P) and the calcium channel antagonist diltiazem (D). The subjects performed standardized tests of muscle power on an isokinetic cycle ergometer following subacute ingestion of N, A, P, D and placebo (PL) in a double blind crossover trial. Subjects exercised maximally for 10 s at 90, 110, 120, 130 and 150 rpm with 2-min rest between sessions. Thereafter, they performed a 30-s fatigue test at 120 rpm. Resting heart rate was decreased 13.4%, 21.9% and 14.6% by N, A and P, respectively (P < 0.05 vs PL). Resting systolic blood pressure was decreased 6.7% by A only (P < 0.05 vs PL). Peak power, average power and work done was not different among treatment groups at any crank velocity, nor was there any difference in total work done or rate of work decline in the 30-s test. We concluded from our study that peak isokinetic muscle power during maximal exercise of short duration is not affected by beta-blockade or the calcium antagonist diltiazem. Fatigue during beta-receptor antagonism would not appear therefore to be due to changes in the ability of skeletal muscle to produce peak power output during exercise of short duration.

Fine needle cytology--is aspiration suction necessary? A study of 100 masses in various sites.

One hundred consecutive superficial mass lesions in various body sites were sampled by both conventional fine needle aspiration (FNA) and by a fine needle without the application of syringe suction. The latter technique is based on the principle of capillarity and may be termed "fine needle capillary" (FNC) sampling. The two sampling techniques were compared using five objective parameters: (1) the amount of diagnostic cellular material present, (2) the retention of appropriate architecture and cellular arrangement, (3) the degree of cellular degeneration, (4) the cellular trauma and (5) the volume of obscuring background blood and clots. There was no statistically significant difference between the efficacies of the two sampling techniques for any of the parameters studied. FNA sampling was diagnostic in a greater number of cases than was FNC sampling, but this difference was not statistically significant at a level of P = .05. When FNC sampling was diagnostic, it more frequently produced superior-quality material; conventional FNA, although diagnostic in a greater number of cases, mostly produced adequate, rather than superior-quality, material. This trend was not, however, statistically significant at a level of P = .05. These findings differ from those of previous studies (which have shown overall superiority of FNC sampling over conventional FNA sampling) and suggest that the technique of fine needle sampling employed for cytodiagnosis can be left to the personal preference of the operator.

Fine-needle aspiration of the liver: out of the ivory tower and into the community.

This study of 160 consecutive fine-needle aspirates of localized hepatic masses analyzed the efficacy of the technique when extended into a multicenter setting. The aspirates were processed and interpreted by a single cytology service, but they were performed, under radiographic imaging, in eight different hospitals by at least 20 radiologists, few of whom had had the opportunity to acquire long-term experience. Of 108 malignancies, 101 were correctly sampled (sensitivity, 93.5%), including 30 primary hepatocellular carcinomas, 70 metastatic tumors, and 1 lymphoma. Specific benign pathologic lesions in 12 cases were amenable to cytodiagnosis. The problem of the remaining 47 samples, which contained exclusively blood, necrotic material, or normal and reactive hepatic constituents, was addressed at length. These were considered "nondiagnostic" samples in the context of aspirating focal masses. The majority had benign lesions on further study, but tumors were found in seven, all of which had been sampling errors, resulting in a negative predictive value of 82.5%. Fine-needle sampling of localized lesions, particularly neoplasms, can thus perform well in transition from single-center studies to more widespread usage in daily practice. Confident reliance on the procedure can be maintained if appropriate radiologic and cytologic facilities exist, provided that the limitations of nonneoplastic aspirates are fully understood.

The aspiration cytology of pulmonary hamartomas.

Cytodiagnosis of pulmonary hamartomas (PHs) by transthoracic fine-needle aspiration (FNA), successful in 11 of a series of 14 cases, has been found to rely less on the presence of mature cartilage than on the recognition of fibromyxoid fragments. These fragments, wispy yet discrete, consisting of variable numbers of fibroblasts embedded in fibrillary ground substance, can be distinguished from fibrous tissue and mucus, both of which they may resemble. Mature cartilage is distinctive when present, but it is seen in a minority of cases. Bronchial cells and adipocytes, integral components of PHs, are of no diagnostic value unless associated with fibromyxomatous tissue or cartilage. Chest wall "contaminants" that may cause pitfalls in diagnosis, such as bone, skeletal muscle, and fibrous tissue, are described and illustrated. The differential diagnosis of biphasic lesions containing epithelial cells and mesenchyme, including dermoids and blastomas, is discussed. With knowledge of the radiologic appearance of target lesions, confident cytodiagnosis of PHs is possible if attention is paid to subtle, yet specific, background features in aspirated material.

Cervical endometriosis: facilitated diagnosis by fine needle aspiration cytologic testing.

Regarded as infrequent, endometriosis of the cervix probably occurs more commonly than is generally realized. The lesion's apparent rarity may be ascribed to limited awareness of the clinical appearance, combined with technical difficulty in obtaining suitable biopsy material for confirmation. A consequence of previous cervical trauma, endometriosis of the cervix can be expected to increase in incidence with more widespread use of invasive cervical procedures. Clinical recognition and tissue confirmation thus become essential. This paper refocuses attention on cervical endometriosis by documenting the clinical, colposcopic, and histopathologic findings in 16 cases seen at a single colposcopy clinic over a 6-month period. Diagnosis in these patients was facilitated and improved by fine needle aspiration cytologic testing. This technique, not previously used for documentation of endometriosis in this location, is outlined in detail, together with a full description and illustration of the cytologic features.

Response of hypersensitive mice to the footpad injection of living homologous or heterologous mycobacteria: preliminary report.

Mice sensitized by the injection of viable mycobacteria into one of the hind footpads responded to a second injection of mycobacteria (3 to 4 weeks later), introduced into the contralateral foot, with a degree of footpad swelling that was both accelerated and exaggerated beyond that observed after the first inoculation. The degree of specificity of this reaction (i.e., response to homologous versus heterologous mycobacteria) was comparable to that previously reported for dermal reactions of hypersensitive guinea pigs to tuberculin or tuberculin-like antigens from mycobacteria. In preliminary studies it was impossible to achieve this state of specific sensitization by vaccinating mice subcutaneously with water-in-oil emulsions of heat-killed mycobacteria; reasons for the failure are discussed. It is suggested that this tool could prove useful in both taxonomic and immunological investigations. Advantages and disadvantages of the mouse footpad test in relation to the dermal skin test in guinea pigs are discussed.