Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women.

Oral N-acetylcysteine supplementation in nine young healthy females induced a quick and highly significant decrease in plasma homocysteine levels and an increase in whole blood concentration of the antioxidant glutathione. N-acetylcysteine impresses as an efficient drug in lowering homocysteine concentration and might be beneficial for individuals with hyperhomocysteinemia who are at increased risk of cardiovascular disease.     

9p21 and 13q14 dosages in ependymomas. A clinicopathologic study of 101 cases.

Ependymomas are glial neoplasms whose clinical behavior is difficult to predict based on histology alone. Recently, a comparative genomic hybridization study identified frequent chromosome 9p and 13q losses in anaplastic ependymomas, suggesting that p16 and RB alterations may be involved in tumor progression. In order to test this hypothesis further, 101 myxopapillary, conventional, and anaplastic ependymomas (51 spinal and 50 intracranial tumors) were tested for RB and p16 deletions using fluorescence in situ hybridization. Clinical follow-up, ranging from 2 to 198 months (median 46 months), was obtained in 90 cases (91%). RB and p16 deletions were seen in 22 of 92 (24%) and 22 of 89 (25%) informative cases, respectively. Polysomies were more frequent in the grade I and II spinal tumors, consistent with prior reports of increased aneuploidy in such cases. No significant genetic associations were seen with tumor grade, recurrence, or death, suggesting that 9p and 13q deletions do not play a prominent role in the malignant progression of ependymomas, as has been implicated in other glioma subtypes.     

Comparison of DSM-III-R and childhood autism rating scale diagnoses of autism

The purpose of this study was to clarify the issue of whether DSM-III-R (American Psychological Association [APA], 1987) over-or underdiagnoses autism by comparing this diagnostic system to a well-established objective measure of diagnosis, the Childhood Autism Rating Scale (CARS). A secondary goal was to determine which of the 16 criteria are the best discriminators of autism. DSM-III-R, CARS, and clinical diagnoses of 138 consecutive admissions to a statewide program for the diagnosis and treatment of autistic and related communication-handicapped individuals (Division TEACCH in North Carolina) were compared. Results indicated a generally high degree of agreement on the diagnosis of autism using the three systems. Within this tratment-oriented program, the CARS and clinical ratings diagnosed a greater number of cases as autistic than did the DSM-III-R criteria, suggesting that DSM-III-R slightly underdiagnosed autism. The criteria that most strongly related to the diagnosis of autism regardless of the system were lack of awareness of others, abnormal social play, an impaired ability to make friends, abnormal nonverbal communication, stereotypic body movements, and restricted range of interests.     

Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.     

Management of common bile duct stones

Conclusions Choledocholithiasis remains a complicated and challenging disease process for today’s clinicians. Transabdominal ultrasound and ERC are the most common preoperative imaging modalities with endoscopic ultrasound, MRCP, and HCT emerging as potentially more accurate and less invasive tools. Intraoperatively, LUS and IOC are complimentary in detecting CBD stones, while laparoscopic CBDE is commonly and safely performed by surgeons comfortable with advanced laparoscopic techniques. Postoperative ERC is effective with failure of laparoscopic CBDE, surgeon inexperience, and unfavorable anatomy and patient selection. Open CBDE should never be looked upon as a failure, while sphincterotomy, sphincteroplasty, and choledochoenterostomy remain necessary operations for certain patients. The proposed algorithm is only a guideline, and ultimate treatment depends on physician experience and available resources.     

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.     

Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.

Adult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial wound cap over the amputation site by 12 h post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were ip injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3, and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two-fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two-fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.     

Changes in blood pressure and vasoactive hormones during volume expansion in stable patients on chronic haemodialysis

Summary: We studied changes in blood pressure (BP) and plasma hormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], endothelin [ET], angiotensin [AII] and renin [PRA]) in four stable haemodialysis patients 48 h after a routine dialysis (basal stat), after volume expansion (4–7% above dry bodyweight) for 4 days then 48 h later following ultrafiltration. Blood pressure rose and plasma AII and PRA values fell with volume expansion and returned to baseline at the end of the study. Endothelin values were unchanged. Plasma ANP and BNP rose similarly in three patients and returned to near baseline levels after ultrafiltration. Sustained volume expansion over 4 days in dialysis patients is associated with an increase in BP, a marked elevation in plasma ANP and BNP but without change in ET.     

Axial myopia in eyes with optic nerve hypoplasia

Given that abnormal visual experience during post natal development interferes with emmetropization, we proposed that eyes with hypoplastic optic nerves were predisposed to the development of refractive errors. Six of 14 patients with unilateral optic nerve hypoplasia and 5 of 22 patients with bilateral involvement had at least 4 D of myopia. Nine of the 11 patients with asymmetric bilateral involvement had relative myopia in the eye with the more abnormal optic nerve; none of the patients with symmetric bilateral involvement had a significant interocular refractive difference. Analysis of axial length measurements obtained in 10 of the 11 patients with high myopia showed a significant increase in total axial length. The presumed normal eye of patients with unilateral involvement was significantly smaller than the mean value for age-adjusted normals. We suspect that visual input to the central nervous system is one of the feedback signals involved in the regulation of ocular growth.Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Florida, May 4, 1990Correspondence to: A.H. Weiss