Psoriasis during therapy with olanzapine

The role of several drugs (lithium, betablockers, clonidine, digoxin, nonsteroidal anti-inflammatory agents, interferon and tetracyclines) in inducing or exacerbating psoriasis is not completely understood. We report two cases of psoriasis in patients treated with olanzapine, a new drug used for psychotic disorders. In the first patient worsening of a pre-existing mild psoriasis occurred shortly after starting olanzapine treatment, followed by a relapse of the dermatological disease after a new administration of the anti-psychotic drug. In the second case we observed the onset of psoriasis during olanzapine treatment in an individual without any previous history of psoriasis but with a family history of the disease. Although the mechanism by which psoriasis may be induced or exacerbated by olanzapine remains unknown, these observations underline the need for caution and close follow-up in the pharmacological management of patients with psoriasis or a family history of the disease.     

3-Hydroxyglutaric acid induces oxidative stress and decreases the antioxidant defenses in cerebral cortex of young rats

Glutaryl-CoA dehydrogenase deficiency (GDD) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of glutaric, 3-hydroxyglutaric (3-OHGA) and glutaconic acids and clinically by severe neurological symptoms and cerebral atrophy whose pathophysiology is poorly known. In the present study we investigated the effect of 3-OHGA, considered the main neurotoxin in GDD, on the lipoperoxidation parameters chemiluminescence and thiobarbituric acid-reactive species (TBA-RS), and on the amount of nitric oxide metabolites in cerebral cortex of young rats. Total radical-trapping antioxidant potential (TRAP), which reflects the tissue antioxidant defenses, was also examined. We observed that 3-OHGA significantly increased chemiluminescence, TBA-RS and nitric oxide metabolites, in contrast to TRAP, which was decreased by the metabolite. The data indicate a stimulation of lipid peroxidation and free radical production, and a reduction of the tissue antioxidant defenses caused by the metabolite. In case these findings also occur in the human condition, it may be presumed that oxidative stress is involved in the brain damage observed in GDD.     

Increased bone turnover in prepubertal,pubertal, and postpubertal patients receiving carbamazepine

PURPOSE: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy. METHODS: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex- and age-matched healthy children. RESULTS: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism. CONCLUSIONS: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.     

异常的口腔血管网模式：唐氏综合征的一种新的临床征象

唐氏综合征主要是遗传原因所导致的精神发育迟滞。在这里,作者对该病患儿(n=14)及其表型正常的父母的口腔血管网的高分维、Lem pel-Ziv复杂性和更低的最小道分维(P≤0.0006)进行描述。这种被公认的新征象可以为识别父母生育唐氏综合征患儿潜在的风险提供一种有用的表型标记物。     

Loss of heterozygosity and microsatellite instability at chromosomal sites 1Q and 10Q in morphologically distinct regions of late stage prostate lesions

PURPOSE: We investigated the incidence of loss of heterozygosity (LOH) and microsatellite instability in sporadic prostate cancer and surrounding tissue at loci encompassing the HPC1 and PTEN genes. MATERIALS AND METHODS: Surgical specimens from 63 patients with sporadic stage T3 or T4 prostatic adenocarcinoma were analyzed for LOH and microsatellite instability. Microdissected tissue included morphologically normal foci, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma. LOH analysis was performed using 4 microsatellite markers that map in the region of the 1q24 to 25 locus of the putative prostate cancer susceptibility gene HPC1 and 4 that map in the region of the 10q23 locus of the PTEN gene. RESULTS: The incidence of LOH on 10q was consistent with that previously reported in prostatic tumors. LOH associated with the PTEN locus was recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence analysis of PTEN in a limited number of lesions revealed mutations in nontumor and tumor tissue. Analysis of the DS10215 locus showed significant LOH in tumor but not in benign tissue, suggestive of a tumor suppressor gene in this region associated with prostatic neoplastic progression. In contrast, no significant LOH was observed in the same tissues at 4 loci on chromosome 1q. In this study we recorded elevated levels of microsatellite instability in benign prostatic tissue with an additional increase associated with prostatic adenocarcinoma. CONCLUSIONS: The low incidence of LOH in the region of the HPC1 locus in all prostate lesions studied suggests that this putative hereditary prostate cancer susceptibility locus does not appear to have a role in sporadic prostate cancer, at least not in the context of LOH. In contrast, analysis of the same tissues for LOH at chromosome 10q confirmed frequent alterations in this region linked to late stage prostate cancer. PTEN mutations in microdissected morphologically normal and BPH tissue showed alterations in nontumor tissue surrounding adenocarcinoma. Microsatellite instability was increased in adenocarcinomas over an elevated background recorded in surrounding tissues.     

Induction chemotherapy plus high-dose radiotherapy versus radiotherapy alone in locally advanced unresectable non-small-cell lung cancer

Background: High-dose radiation therapy is generally recommendedas standard treatment in regionally advanced unresectable non-small-celllung cancer (NSCLC), but medianand long-term survival remainpoor. Some reports have recently shown an improvement of resultsin advanced NSCLC when cisplatin was included in the chemotherapyregimens. Therefore, we designed a randomized trial to determinewhether induction chemotherapy before high-dose radiotherapyimproves response rate and survival in stage HI NSCLC over thatachieved with radiotherapy alone. Patients and methods: From March, 1984 to December, 1988, 66consecutive patients with stage HI unresectable NSCLC were randomizedto one of two treatment arms; 61 were evaluable for survivaland 58 for response and toxicity. Patients randomly assignedto arm A received cisplatin (CDDP 100 mg/m² on day 1) and etoposide(VP 16 120 mg/ m² on days 1, 2, 3) every 3 wks for 3 coursesfollowed by radiotherapy 56 Gy on pre-treatment tumor volumeand 40 Gy on mediastinum and bilateral supraclavicular nodes.Patients assigned to arm B received only the same radiotherapy.The 61 eligible patients were comparable in terms of age, performancestatus, histology and treatment. Results: Response rate was 53% in arm A and 32% in arm B. Themedian survival was 52 wks for the combined treatment arm and36 wks for the radiation therapy arm. At six years of follow-upall the patients were dead. Toxicity was mild and no treatment-relateddeaths were recorded. Conclusion: Induction chemotherapy produced a better responserate and a trend of improved survival (4 months) but a significantsurvival advantage was not achieved (p < 0.11), probablybecause of the small number of patients enrolled in the trial. chemotherapy, non-small-cell lung cancer, radiotherapy, combined treatment     

Gender differences in 24-hour urinary diaries of asymptomatic North American adults

PURPOSE: Two previously published studies from our center have described the urinary habits of asymptomatic men (284) and women (300) as revealed by 24-hour urinary diaries. Those gender specific studies found that urinary diary variables are affected by age and race. By comparing the data from those studies we determined the effect of gender on voiding habits. MATERIALS AND METHODS: In this secondary analysis we matched each female urinary diary to that of a male of similar age and race. Diary variables were compared using paired sign tests with results considered significant at the 5% level. RESULTS: A total of 141 matched pairs were studied. The population age ranged from 18 to 68 years and was racially diverse (56% black, 31% white, 7% Hispanic and 6% Asian). Men had higher total fluid intake and mean voided volume than women (p <0.001 and 0.04, respectively). Women voided more frequently than men (p = 0.006) and had more voids per liter of fluid intake (p <0.001). No gender differences were found for body mass index, nighttime or daytime diuresis rates, total urine volume, maximum voided volume or rates of nocturia. CONCLUSIONS: This analysis suggests that there are significant gender effects on 24-hour diary variables, with females tending to void more often and at lower mean volumes. The results of our study may be useful in the design of research studies or for patient counseling.