Quinine potently blocks single K+ channels activated by dopamine D-2 receptors in rat corpus striatum neurons

In single channel recordings from acutely dissociated neurons of the rat corpus striatum, a membrane K+ channel which is activated by dopamine D-2 receptors was blocked by nanomolar concentrations of quinine. An intermittent partial blockade was observed at 4-10 nM quinine, with a voltage dependence consistent with quinine binding to the channel near the extracellular surface of the membrane. A nearly complete blockade of channel current was observed at 100 nM quinine and above. Such concentrations are known to be too low to block various other ion channels, and may be attained in human brain at antimalarial dosages of quinine. Blockade of this channel by quinine may provide a useful experimental probe of dopaminergic function, as an alternative to D-2 receptor binding site blockade by neuroleptics.     

Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Platelet cold agglutinins: a flow cytometric analysis.

Spontaneous EDTA-independent cold platelet agglutination is a rare phenomenon that produces pseudothrombocytopenia when blood samples are analyzed in automated cell counters. We report a case of platelet cold agglutinins and an analysis by flow cytometry. A 49 year old woman presented with abnormal vaginal bleed secondary to uterine fibroids. Platelet clumping was observed in blood samples taken in EDTA-, heparin- and citrate-containing tubes. In flow cytometric tests, patient serum agglutinated 16% of normal platelets at 22 degrees C, and 7% of platelets after incubation at 37 degrees C; in contrast, 3% and < 1% of platelets were agglutinated at 22 and 37 degrees C, respectively, after incubation with normal serum. Minimal agglutination (< 10%) was observed with patient serum at a titre of 1:5 or at temperatures > 30 degrees C. After incubation at 4 degrees C, IgM antibody and C3 were increased on the patient's platelets; no significant amount of IgM or C3 was detected on normal platelets. The specificity of the platelet cold agglutinin was determined by competitive inhibition by monoclonal anti-CD41(GPIIbIIIa). Before the addition of monoclonal antibody, patient's serum agglutinated 16% of normal platelets at 22 degrees C; after addition of anti-CD41 only 2% of the platelets were agglutinated. This blocking effect was not observed with anti-CD42. The patient's platelets functioned normally as determined by CD62 and CD63 expression in response to thrombin, normal platelet aggregation in response to collagen, ADP, and ristocetin, and a normal template bleeding time. In summary, platelet agglutination by a platelet cold agglutinin was quantitated by flow cytometry, the responsible antibody was characterized as a low titre IgM with minimal activity > 30 degrees C, and competitive binding studies supported the GPIIbIIIa complex as the binding site for the antibody. Since the antibody did not affect platelet function, we believe that these patients will not suffer complications from their platelet cold agglutinin, but it could pose a problem under circumstances such as cardiac surgery with hypothermia.     

Coronary venous retroperfusion of arterial blood for the treatment of acute myocardial ischemia

Synchronized coronary venous retroperfusion of autologous arterial blood was offered to patients referred for medically refractory unstable angina or evolving myocardial infarction with contraindications to thrombolytic therapy. Primary endpoints of angina, ST segment deviation, and two-dimensional echocardiographic systolic wall motion were followed to determine the efficacy of retroperfusion in patients prior to and then during angioplasty, surgical intervention, or pharmacological management, as the clinical picture warranted. Over a 12 month period, 21 patients were referred and 15 received retroperfusion. All experienced full relief of angina (p = 0·008). ST segment deviations and systolic wall motion of ischemic zones were observed to improve (p = 0·06 ST changes; p = 0·0001 wall motion changes) with synchronized retrograde perfusion. During attempts to remove patients from retroperfusion, statistically significant (p < 0·01) reproducible changes in these same endpoints were documented. Retroperfusion appears to improve acute myocardial ischemia. This technique functions well in the intensive care unit environment with only fluoroscopy as technical imaging support.     

Event-related potential correlates of functional hearing loss: Reduced P3 amplitude with preserved Nl and N2 components in a unilateral case

Abstract A female patient exhibiting functional hearing loss in her left ear demonstrated reduced amplitude of P3 component in event-related potentials (ERP) to left monaural stimulation, with preserved N1 and N2 components to stimulation of either ear. This result suggested that stimuli in the affected ear were conducted successfully up to the auditory cortex but that further processing in higher brain regions was 'repressed'. Event-related potential examination for such hysterical disorders could be useful in clarifying their brain mechanism and offer a useful diagnostic clue to its nature.     

Serum cholesterol levels in a multiracial sample of 7,439 preschool children from Arizona.

BACKGROUND. The distribution and correlates of serum levels of total cholesterol were studied in cross-sectional analyses of 7,439 1 to 4 year olds examined through the Arizona Department of Health Services. RESULTS. Mean cholesterol levels increased with age, and levels among 2 year olds approached those seen in adolescents. Racial and ethnic differences in cholesterol levels were observed: mean (age-adjusted) levels were 147 mg/dl among American Indians (n = 622), 153 mg/dl among Hispanics (n = 3165), 154 mg/dl among non-Hispanic whites (n = 3448), and 163 mg/dl among blacks (n = 204). Cholesterol levels were not associated either with obesity, as assessed by relative weight or the Quetelet index, or with breast-feeding during infancy. Very overweight (greater than or equal to 20 kg/m2) 3 and 4 year olds, however, tended to have higher mean levels of cholesterol than did other children. The proportion of children with borderline (170 to 199 mg/dl) or high (greater than or equal to 200 mg/dl) levels of cholesterol varied by race/ethnicity: borderline (high) levels were seen among 14% (3%) of American Indians and 29% (11%) of blacks. The proportions of white and Hispanic children having cholesterol levels between 170 and 199 mg/dl or greater than or equal to 200 mg/dl were midway between those seen among American Indians and blacks. CONCLUSION. Additional information on the interrelationships of lipids and lipoproteins may aid in the identification of children who will be at increased risk for cardiovascular disease in adulthood.     

Risk of basal cell carcinoma in relation to alcohol intake and smoking.

We prospectively investigated whether alcohol intake and smoking affect the risk of basal cell carcinoma (BCC) in subjects from the United States Radiological Technologists (USRT) cohort study. We evaluated 68,371 radiological technologists certified during 1926-1982 who were free of cancer at the time they answered a first questionnaire (1983-1989) and who completed a second questionnaire (1994-1998). The first questionnaire provided baseline information on numerous risk factors, including smoking and alcohol intake, and the second provided self-reported cancer diagnoses. During 698,190 person-years of follow-up, we identified 1,360 cases of BCC: 1,036 in women and 324 in men. Cox proportional hazards regression indicated that the trend in BCC was significantly associated with increased alcohol intake (P for trend = 0.001). Compared with those who reported no alcohol consumption, those who drank <1-2, 3-6, 7-14, and >14 drinks/week had multivariate risks of 1.1 [95% confidence interval (CI), 0.9-1.3], 1.3 (95% CI, 1.1-1.5), 1.4 (95% CI, 1.2-1.7), and 1.0 (95% CI, 0.7-1.6), respectively. We found no clear association between smoking and BCC. This is the second large prospective study to report a significant but nonmonotonic trend in increased risk associated with alcohol consumption.