Doctors'' characteristics do not predict long-term glycaemic control in type 2 diabetic patients.

Glycaemic control in type 2 diabetic patients varies widely between general practitioners (GPs). To increase our understanding of this variation, linear random effects models were used to examine the predictive value of GP characteristics on the course of annual HbA1c measurements, in 688 newly diagnosed type 2 diabetic patients between one and five years after diabetes diagnosis. We found that characteristics of centrally supported GPs, such as interest in diabetes, experience, practice type, list size, and weekly working hours, did not predict their patients' glycaemic control.     

High-throughput single strand conformation polymorphism mutation detection by automated capillary array electrophoresis: validation of the method

Capillary array electrophoresis (CAE) is a novel technique, which allows for high throughput analysis of DNA fragments. When screening for mutations in whole populations or large patient groups it is necessary to have robust and well-characterized setups for high throughput analysis. For large-scale mutation screening, we have developed procedures for single strand conformation polymorphism (SSCP) assays using CAE (CAE-SSCP) whereby we may increase both the sensitivity and the throughput compared to conventional SSCP analysis. In this study we have validated CAE-SSCP by 1) comparing detection by slab-gel based SSCP with CAE-SSCP of mutations in the MYH7, MYL2, and MYL3 genes encoding sarcomere proteins from patients suffering from hypertrophic cardiomyopathy; and 2) by constructing a series of 185 mutants having substitution mutations, as well as insertion/deletion mutations, or some combinations of these, in different sequence contexts in four exons and different positions relative to the end of the amplicon (three from the KCNQ1 gene, encoding a cardiac potassium channel, and one from the TNNI3 gene encoding cardiac troponin I). The method identified 181 out of 185 mutations (98%), and the data suggest that the position of mutation in the fragment had no effect on the sensitivity. Analysis of the specificity of the method showed that only very few mutants could not be distinguished from each other and there were no false positives.     

Hydrochlorothiazide and potassium chloride in comparison with hydrochlorothiazide and amiloride in the treatment of mild hypertension

A randomized, double-blind, cross-over study comparing 50 mg hydrochlorothiazide plus 5 mg amiloride (HCTZ/A) with 50 mg hydrochlorothiazide plus 26 mmol potassium chloride (HCTZ/K) was conducted in 18 patients with mild essential hypertension (diastolic pressure 90-105 mmHg). The sequence of treatment was: placebo for 2 weeks, one active drug for 3 weeks, placebo for 2 weeks, the other active drug for 3 weeks. The two agents were significantly and equally efficacious in lowering the systolic and diastolic blood pressure. Baseline vs. treatment mean serum potassium levels were 3.82 vs. 3.78 mmol/l for HCTZ/A and 3.82 vs. 3.70 mmol/l for HCTZ/K. The decrease in serum potassium level from baseline was significant for both agents but not significantly different when the two treatment forms were compared. Both treatment forms elevated fasting serum cholesterol and glucose. Serum triglycerides and uric acid rose significantly with HCTZ/K. Amiloride may affect the tubular handling of uric acid causing increased uric acid excretion, thus counteracting thiazide-induced hyperuricemia. During 3 weeks' extension of the main study, 5 patients received HCTZ/A in double the original dose (100 mg/10 mg) and 6 patients received HCTZ/K in double the original dose (100 mg/52 mmol). No further blood pressure reduction was observed on treatment with these doses. The mean serum potassium levels did not decrease further on doubling the HCTZ/A dose, while a significant fall was observed for HCTZ/K (3.60 vs. 3.42 mmol/l) (p less than 0.05, single tailed t-test). Both drug combinations were well tolerated and side-effects were not significantly different from those during placebo administration. This study demonstrates that 50 mg hydrochlorothiazide plus 26 mmol potassium chloride are as effective as 50 mg hydrochlorothiazide plus 5 mg amiloride, both in reducing blood pressure and preventing hypokalaemia in the treatment of essential hypertension. A small extension study indicates that amiloride might be more effective than potassium chloride in preventing hypokalaemia when high doses (100 mg/day) of hydrochlorothiazide are administered.     

Effect of sodium ions on penicillin-induced epileptiform activity in vitro

Summary Intra- and extracellular recordings were obtained from the CA1 region of guinea pig hippocampal slices maintained in vitro. We studied the effect of reducing the extracellular sodium concentration on penicillin-induced epileptiform responses.In control experiments, Tris and choline were assayed as sodium substitutes. Choline was found unsuitable, since it induced repetitive firing in the absence of any convulsant agent. Replacement of 50% of the extracellular sodium ([Na⁺]_o) with Tris reduced the amplitude of the presynaptic fiber volley, the field EPSP, and the population spike. Intracellular studies showed that when [Na⁺]_o was lowered, action-potential amplitudes were reversibly depressed by an amount close to that predicted by the Nernst relation.Orthodromically elicited epileptiform discharges, induced by penicillin, were reduced in a low-sodium medium when constant stimulus currents were employed. If orthodromic stimulus strengths in normal and low-sodium states were equated on the basis of the field-EPSP amplitude, no significant diminution of the depolarizing-wave component of the epileptiform response was observed. These results suggest that a synaptic component underlies penicillin-induced epileptiform discharges.Supported by grants from the Norwegian Research Council for Science and the Humanities and by NIH grants NS 11535 and NS 15772     

IgG antibodies to purified Aspergillus fumigatus antigens determined by enzyme-linked immunosorbent assay

IgG antibodies to three purified Aspergillus fumigatus antigens were determined by enzyme-linked immunosorbent assay (ELISA) in sera from 26 patients with definite pulmonary aspergillosis (group 1), 23 patients with suspected pulmonary aspergillosis (group 2), 8 patients with precipitating antibodies to A. fumigatus of undetermined clinical significance (group 3), and 113 healthy blood donors (group 4). With a 470,000-dalton antigen fraction ELISA values exceeded the upper range of group 4 (0.72) in 92, 91 and 13% of cases in groups 1, 2 and 3, respectively. With a 250,000-dalton antigen fraction the figures were 96, 78 and 13%, respectively (upper range of group 4 = 0.25). With an antigen fraction of 25,000-50,000 daltons the figures were 96, 65 and 13%, respectively (upper range of group 4 = 0.18). In 48 of 49 cases of definite or suspected aspergillosis (groups 1 + 2) ELISA values with at least one antigen exceeded the upper range of controls (group 4). It appears that antibody determination with these three antigen fractions may have a high diagnostic sensitivity.     

Distribution of whaleworm (Anisakis simplex,Nematoda, Ascaridoidea) L3 larvae in three species of marine fish; saithe (Pollachius virens (L.)), cod (Gadus morhua L.) and redfish (Sebastes marinus (L.)) from Norwegian waters

The frequency distribution of Anisakis simplex L3 larvae between host tissues was investigated in three host species: saithe, cod and redfish. Fish were sampled from Norwegian coastal waters and examined for the presence of A. simplex in muscle and viscera. In all three of the host species, A. simplex larvae were most frequently detected in the viscera; the percentages of total infection for saithe, cod and redfish were 99.6%, 97.8% and 88.0%, respectively. In general, the distribution patterns of A. simplex L3 between muscle and viscera were not significantly affected by host size. The observations that distributions vary between species and are not affected by host size do not support an earlier hypothesis which states that A. simplex L3 distributions are determined by an optimal pre-encapsulation migratory distance within host tissues. In contrast, it is suggested that A. simplex L3 distributions are governed by the conditions encountered within host tissues, and are possibly related to the availability of nutrients. Received: 9 July 1997 / Accepted: 15 September 1997     

Muscle fibre type,efficiency, and mechanical optima affect freely chosen pedal rate during cycling

This study investigated the variation in freely chosen pedal rate between subjects and its possible dependence on percentage myosin heavy chain I (%MHC I) in m. vastus lateralis, maximum leg strength and power, as well as efficiency. Additionally, the hypothesis was tested that a positive correlation exists between percentage MHC I and efficiency at pre-set pedal rates but not at freely chosen pedal rate. Twenty males performed cycling at low and high submaximal power output ( approximately 40 and 70% of the power output at which maximum oxygen uptake (VO(2max)) was attained at 80 r.p.m.) with freely chosen and pre-set pedal rates (61, 88, and 115 r.p.m.). Percentage MHC I as well as leg strength and power were determined. Freely chosen pedal rate varied considerably between subjects: 56-88 r.p.m. at low and 61-102 r.p.m. at high submaximal power output. This variation was only partly explained by percentage MHC I (21-97%) as well as by leg strength and power. Interestingly, %MHC I correlated significantly with the pedal rate at which maximum peak crank power occurred (r = -0.81). As hypothesized, %MHC I and efficiency were unrelated at freely chosen pedal rate, which was in contrast to a significant correlation found at pre-set pedal rates (r = 0.61 and r = 0.57 at low and high power output, respectively). Conclusions: Subjects with high percentage MHC I chose high pedal rates close to the pedal rates at which maximum peak crank power occurred, while subjects with low percentage MHC I tended to choose lower pedal rates, favouring high efficiency. Nevertheless, the considerable variation in freely chosen pedal rate between subjects was neither fully accounted for by percentage MHC I nor by leg strength and power. Previously recognized relationships between percentage Type I ( approximately %MHC I) and efficiency as well as between pedal rate and efficiency were confirmed for pre-set pedal rates, but for freely chosen pedal rate, these variables were unrelated.     

Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2

In a four-generation family with long QT syndrome, syncopes and torsades de pointes ventricular tachycardia (TdP) were elicited by abrupt awakening in the early morning hours. The syndrome was associated with a novel KCNH2 missense mutation, G572R, causing the substitution of a glycine residue at position 572, at the end of the S5 transmembrane segment of the HERG K(+)-channel, with an arginine residue. This segment is involved in the channel pore and the mutation may cause a reduction in the rapidly activating delayed rectifier K+ current (Ikr), or changed gating properties of the ion channel, leading to prolonged cardiac repolarization. The electrocardiograms of affected persons showed prolonged QT interval and notched T waves. Despite treatment with atenolol, 200 mg twice daily, the proband still experienced TdP episodes. Three untreated relatives of the proband died suddenly, and unexpectedly, at 18, 32, and 57 years of age. The G572R mutation is thus associated with a high mortality rate, and the clinical presentation illustrates that some mutations may not be controllable by just beta-blockade.     

Screening for cervical cancer in HIV-infected women receiving care in the United States

OBJECTIVE: We examined the sociodemographic, clinical and provider factors associated with screening for cervical cancer among HIV-infected women. METHODS: We studied a national sample representing 43,490 women receiving treatment of HIV infection who completed first follow-up surveys of the HIV Cost and Service Utilization Study (HCSUS). All women were asked, "In the past 12 months, have you had a Pap test?" Women reporting an abnormal Pap test result were asked whether they had been told antibiotics could cure abnormal cells, and whether they were scheduled for another Pap test or for a colposcopy within 3 months. RESULTS: Of the population represented, 81% had had a Pap test in the past 12 months. Women who reported having a gynecologist and primary care physician at the same clinical site were almost twice as likely (odds ratio, 1.9; 95% confidence interval, 1.3-3.0) as other women to report Pap testing. Among women who reported abnormal Pap test results and were not told antibiotics could cure abnormal cells, 95% were scheduled for a repeat Pap test or colposcopy, but 15% of the women had not received their repeat Pap test or colposcopy. CONCLUSION: Although Pap test rates and appropriate referral for abnormal findings were high among HIV-tested women, many women with initially abnormal Pap test results did not actually receive follow-up Pap testing or colposcopy. Providing gynecologic care at the same site as primary HIV care would likely improve delivery of needed gynecologic care for women.