Effects of LY215490, a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, on the micturition reflex in the rat

The effects of glutamate receptor antagonists on urinary bladder and external urethral sphincter- (EUS) electromyogram (EMG) activity were evaluated in unanesthetized decerebrate rats. In normal rats, LY215490, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, in small i.v. doses (1-3 mg/kg) decreased bladder contraction amplitude (BC-Amp) by 29% and EUS-EMG by 41%; whereas a large dose (10 mg/kg) completely abolished bladder and EUS-EMG activity. LY215490 injected intrathecally in small doses (0.01-0.1 microg) decreased BC-Amp by 20% and EUS-EMG by 62%; whereas large doses (1-10 microg) completely abolished bladder and EUS-EMG activity. LY215490 (0.1 microg i.t.) increased bladder capacity by 28% and decreased voiding efficiency by 44%. Combined i.t. administration of small doses of LY215490 (0.1 microg) and MK-801 (1 microg), an N-methyl-D-aspartate (NMDA) receptor antagonist, which individually had little effect on BC-Amp, markedly suppressed bladder activity. In chronic spinal rats, LY215490 (10 mg/kg i.v.) abolished EUS-EMG activity and decreased BC-Amp by 41%. Intrathecal injections of LY215490 were also less effective in chronic spinal rats; a 10-microg dose producing only a partial block (53%) of BC-Amp, but complete block of EUS-EMG. In chronic spinal rats, MK-801 (1 mg/kg i.v.) abolished EUS-EMG activity and decreased BC-Amp by 36%. Pretreatment with MK-801 (1 mg/kg i.v.) did not enhance the effect of LY215490 on bladder activity in chronic spinal rats. These data suggest that AMPA glutamate receptors have a major role in the excitatory pathways controlling bladder and EUS activity in spinal cord intact rats. However, in chronic spinal rats, AMPA and NMDA receptors are essential for EUS reflexes, but are responsible for only a part of reflex bladder activity.     

Subjective interpretation, laboratory error and the value of forensic DNA evidence: three case studies

This article discusses two factors that may profoundly affect the value of DNA evidence for proving that two samples have a common source: uncertainty about the interpretation of test results and the possibility of laboratory error. Three case studies are presented to illustrate the importance of the analyst's subjective judgments in interpreting some RFLP-based forensic DNA tests. In each case, the likelihood ratio describing the value of DNA evidence is shown to be dramatically reduced by uncertainty about the scoring of bands and the possibility of laboratory error. The article concludes that statistical estimates of the frequency of matching genotypes can be a misleading index of the value of DNA evidence, and that more adequate indices are needed. It also argues that forensic laboratories should comply with the National Research Council's recommendation that forensic test results be scored in a blind or objective manner.     

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.     

Sex difference in the mortality trends of acute myocardial infarction in Taiwan, 1974 to 1993

The nutritional status of 75 maintenance hemodialysis (MHD) patients was evaluated according to the dietary intake analysis, anthropometric measurements, biochemical and immunological parameters in this study. Furthermore, some possible factors which would affect nutritional status of hemodialysis patients were discussed. The results showed that hemodialysis patients demonstrated a high incidence of malnutrition. The low intake of protein and calorie, metabolic acidosis and inadequate dialysis would worsen the malnutrition while erythropoietin treatment improve the nutritional status of hemodialysis patients. Based on these results, suggestions were proposed for the improvement of nutritional status of MHD.     

Lumbar spine magnetic resonance imaging: comparison between fast spin echo proton density and spin echo T1 axial scans

Spin echo (SE) T1 axial scans are routinely obtained in magnetic resonance imaging of the lumbar spine in many centres. This study directly compared matched SE T1 and fast SE (FSE) proton density (PD) axial scans. Both SE T1 and FSE PD axial scans of the lumbar spine were obtained in 116 consecutive patients. The imaging parameters (field-of-view, slice thickness, interslice gap, number of excitations and matrix size) and scan levels were identical for each pair of sequences. At two selected levels, L4/5 and L5/S1, various structures were independently graded by two observers. In 232 lumbar levels analysed, the bone marrow, epidural fat, disc, extradural nerve root and facet joint were equally well seen on both sequences by both observers (combined mean grades of 2.93-2.99). The thecal sac was marginally better depicted on FSE PD than on SE T1 images, with mean grades of 2.96 and 2.88, respectively. The psoas muscle was adequately visualized for diagnostic purposes on both sequences (mean grades of 2.30-2.32). The cauda equina were better seen on FSE PD (mean grade 1.92) than on SE T1 (mean grade 1.00) images. In conclusion, FSE PD scans are comparable to and may potentially replace SE T1 axial MR scans of the lumbar spine.     

Improvements in daily functioning after deep brain stimulation of the thalamus for intractable tremor

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.     

Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy

Retrograde transport from the Golgi to the ER is an essential process. Resident ER proteins that escape the ER and proteins that cycle between the Golgi and the ER must be retrieved. The interdependence of anterograde and retrograde vesicle trafficking makes the dissection of both processes difficult in vivo. We have developed an in vitro system that measures the retrieval of a soluble reporter protein, the precursor of the yeast pheromone alpha-factor fused to a retrieval signal (HDEL) at its COOH terminus (Dean, N., and H.R.B Pelham. 1990. J. Cell Biol. 111:369-377). Retrieval depends on the HDEL sequence; the alpha-factor precursor, naturally lacking this sequence, is not retrieved. A full cycle of anterograde and retrograde transport requires a simple set of purified cytosolic proteins, including Sec18p, the Lma1p complex, Uso1p, coatomer, and Arf1p. Among the membrane-bound v-SNAP receptor (v-SNARE) proteins, Bos1p is required only for forward transport, Sec22p only for retrograde trafficking, and Bet1p is implicated in both avenues of transport. Putative retrograde carriers (COPI vesicles) generated from Golgi-enriched membranes contain v-SNAREs as well as Emp47p as cargo.     

Three-dimensional CT scan of hemimandibular hyperplasia: case report

Transient absorption spectra of adenine, adenosine and 2'-deoxyadenosine 5'-monophosphate (dAMP) arising from 248 nm laser flash photolysis using acetone as a photosensitizer have been observed. The intermediates recorded are assigned to the excited triplet states and dehydrogenated radicals of adenine and its nucleoside and nucleotide. The excited triplet states of adenine and its derivatives are produced via triplet-triplet excitation transfer and observed for the first time, while the dehydrogenated radicals stemming from the interaction of triplet acetone with adenine and its derivatives via electron transfer through a five-member-ring electron donor-acceptor intermediate. The site of dehydrogenation is suggested to be the hydrogen atom on C(8) of the adenine moiety. Moreover, three sets of kinetic parameters of the triplet decay have been determined. The rate constants of the unimolecular decay (k0), the triplet quenching by the ground state (ksq) and by the triplet quencher Mn2+ (kq) are 1.1 x 10(5), 7.9 x 10(4), 3.7 x 10(4) s-1, 6.9 x 10(8), 8.3 x 10(8), 3.6 x 10(8) dm3 mol-1 s-1 and 4.2 x 10(8), 3.5 x 10(8), 6.0 x 10(8) dm3 mol-1 s-1 respectively for adenine, adenosine and dAMP.