A randomized, double-blind, crossover comparison of risperidone and haloperidol in Korean dementia patients with behavioral disturbances.

OBJECTIVE: Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. METHODS: This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5-1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. RESULTS: Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. CONCLUSION: Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.     

Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes.

The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.4-fold higher than those from the R-form, respectively. The sums of formation Clint of both metabolites were 13.5 and 57.3 microl/min/mg protein for R- and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The p450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Clint values of hydroxy and sulfone metabolite formation catalyzed by all these p450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Clint between S- and R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Clint 76.5 versus 10.8 microl/min/nmol of p450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Clint between S- and R-enantiomers (179.6 versus 143.3 microl/min/nmol of p450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (Km 2.3 versus 13.1 microM), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses.     

Factors affecting penetration of zona-free hamster ova

The sperm penetration assay is an expensive, time-consuming test to assess male fertility in vitro. Although some investigators are enthusiastic in its application, others feel that it is not sensitive or specific enough to be used as part of the routine infertility evaluation. Indeed, this bioassay is not a faithful reproduction of in vivo conditions. However, if the SPA is abnormal, it is unlikely that sperm will fertilize a human ovum in vivo. Conversely, a normal SPA does not guarantee successful in vivo fertilization. No bioassay can be absolute in its predictive value, but false-negative results must be kept to a minimum for this bioassay to be of any clinical significance. Each laboratory performing the SPA should optimize the assay for sensitivity, reproducibility, and minimization of false-negative results and then establish normal and abnormal ranges of its own. If the limitations of the SPA are kept in mind, and if we employ it very selectively, it may still be useful.     

Study on the mechanism of an experimental immunological intrahepatic cholestasis model.

Tuberculin-sensitized guinea pigs were intravenously injected with heat-killed Propionibacterium acnes followed by an intravenous injection of purified protein derivatives 7 day later, resulting in the induction of intrahepatic cholestasis. Using this experimental model, the following results were obtained: (1) Both uptake and release of bile acid were inhibited in the hepatocytes prepared from the cholestasis guinea pigs. (2) The results of the erythritol clearance method indicated that the decrease in bile flow observed in the cholestasis guinea pigs was mostly attributable to the reduced bile excretion from the canaliculi. (3) The decrease in the formation of bile acid independent bile flow was the cause of the decrease in bile flow observed in the cholestasis guinea pigs. (4) There was no change in the permeability of the interhepatocellular tight junction in the cholestasis guinea pigs.     

Ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia.

OBJECTIVE: To evaluate the ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia. DESIGN: Prospective, single blind study. PATIENTS: A total of 41 patients with post-stroke hemiplegia were included (24 men and 17 women, mean age 56 years (standard deviation 11), age range 34-78 years). METHODS: Clinical evaluation of the affected shoulder was assessed using the Motricity Index scores and the Modified Ashworth Scale. Two ultrasonographic measurements were taken to check intra-rater reliability. The shoulder subluxation ratio was determined as the ratio of the radiographic vertical and horizontal distance, and the ultrasonographic lateral and anterior distances in the affected shoulder divided by that in the unaffected shoulder. RESULTS: Intraclass correlation coefficients of the repeated ultrasonographic lateral/anterior distance measurements in the unaffected and affected shoulders were 0.979/0.969 and 0.950/0.947, respectively. Ultrasonographic lateral/anterior distance ratios were negatively correlated with Motricity Index scores of the affected shoulder abduction (r = -0.490, p < 0.001/ r = -0.671, p < 0.001). Ultrasonographic anterior distance ratio was negatively correlated with Modified Ashworth Scale score of the affected shoulder (r = -0.374, p < 0.05). However, there was no correlation between radiographic distance ratios and clinical evaluation scores. CONCLUSION: We strongly recommend ultrasonography as a diagnostic tool to measure the degree of shoulder subluxation in patients with post-stroke hemiplegia.     

Primary Adenocarcinoma in the Urethrorectal Fistula

A 60-year-old Japanese man was hospitalized because of urinary leakage from the anus on October 3, 1994. Retrograde urethrography detected a fistula between the bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma. Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were performed. Pathological examination revealed primary adenocarcinoma in the fistula with invasion to the prostatic urethra and bladder wall. The patient showed no evidence of a recurrence as of August, 1996.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

A SLAP lesion associated with calcific tendinitis of the long head of the biceps brachii at its origin

Calcific tendinitis is a common condition with characteristic clinical and radiological findings. Although we do not know which condition initiated the pathologic cascade, we present a rare case of calcific tendinitis of the long head of the biceps brachii at its origin, associated with a SLAP lesion. The calcium deposit was removed and the SLAP lesion was repaired with a suture anchor arthroscopically.