Dopamine antagonists reduce spontaneous electrical activity in cultured mammalian neurons from ventral mesencephalon

Mammalian neurons from ventral mesencephalon (VM) were grown in primary dissociated cell (PDC) culture. These neurons are predominantly non-dopaminergic. Many of these non-dopaminergic neurons have dopamine agonist and antagonist binding sites. Intracellular recordings were obtained from these neurons. When bathed in phosphate-buffered saline (PBS) solution they generated action potentials spontaneously. However, in the presence of haloperidol dissolved in PBS solution, the percentage of neurons which generated action potentials spontaneously was reduced in a dose-dependent manner (1–10 μM). This response was also obtained with (+) butaclamol (1 μM) but not with (−) butaclamol (1 μM). This neuroleptic inhibition of spontaneously generated action potentials was specific for neurons in PDC cultures of VM since neurons in PDC cultures of spinal cord did not demonstrate this phenomenon.     

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.     

Measurement of immunoreactive myelin basic protein peptide (45-89) in cerebrospinal fluid

To measure myelin basic protein (MBP)-like material in cerebrospinal fluid, we compared two radioimmunoassays, both using the same antiserum to MBP but one using peptide (45-89) as the radioligand and standard (peptide assay), and the other using purified MBP as the radioligand and standard (MBP assay), with respect to their diagnostic sensitivity. Cerebrospinal fluid specimens from 185 patients with definite multiple sclerosis (MS) (n = 27), possible MS (n = 63), probable MS (n = 24), and other neurological disease (n = 71) were analyzed using both assays. The diagnostic sensitivity of the peptide assay was significantly better than that of the MBP assay in those with definite MS (sensitivity 59% and 30%, respectively); there was no significant difference in specificity. The peptide assay also showed better correlation with disease activity than the MBP assay: 14 patients classified as having active MS showed significantly higher sensitivity (78.6% versus 38%, p less than 0.04) when compared to patients with inactive disease. The MBP assay showed no significant difference between these two groups. Besides the increase in sensitivity, the actual molar concentrations of immunoreactive MBP detected using this peptide assay were considerably higher than those found using the MBP assay. These results show that the use of MBP antisera capable of recognizing epitopes present in the carboxyl half of MBP peptide (45-89) results in more sensitive detection of immunoreactive MBP when used with MBP peptide (45-89) as radiolabeled ligand in the assay.     

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.     

Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions

Portwine stains were examined before, immediately after, and 1 yr after successful clearance by a pulsed dye laser (577 nm) using ultrastructural techniques. Dilated vascular channels and mast cell hypoplasia characterized lesional skin before treatment. Immediately after treatment, widespread selective vessel necrosis, similar to changes previously described, was observed. One year after laser irradiation, the abnormally ectatic portwine stain vessels had been replaced by small venules and arterioles, similar in number and diameter to blood vessels in normal skin; the only difference noted was that these new vessels were surrounded by easily identifiable mast cells. Many of these mast cells exhibited evidence of activation and degranulation. We conclude that mast cells may play an important role in the neovascularization of portwine stains treated by 577-nm dye laser irradiation.     

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.     

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