Excitatory and inhibitory amino acid binding sites in human dentate nucleus

Autoradiography of excitatory and inhibitory amino acid binding sites in human dentate nuclei indicated virtually no binding toN-methyl-d-aspartate (NMDA) or γ-aminobutyric acid_B (GABA_B) binding sites, and a low density of kainate binding sites. -Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, metabotropic-quisqualate, benzodiazepine, and γ-aminobutyric acid_A (GABA_A) binding sites were present in moderate abundance. Our NMDA results differ from those found previously in rodents. GABA_A receptors are probably the primary mediators of inhibitory neurotransmission and -amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic-quisqualate receptors are probably the primary mediators of excitatory neurotransmission within the human deep cerebellar nuclei.     

Stethoscope acoustics and cervical auscultation of swallowing

Frequency response characteristics of six popular stethoscopes are reported for the higher frequency range (to 3000 Hz) to supplement equivalent measurements for the lower frequencies (35–1000 Hz) published previously. Spectra of the sounds of swallowing from the throat, transduced with an accelerometer, demonstrate important frequency composition in this higher range. Two stethoscope models were found to have superior transmission characteristics for use in cervical auscultation of swallowing sounds.     

Quisqualate- and NMDA-sensitive [3H]glutamate binding in primate brain

Excitatory amino acids (EAA) such as glutamate and aspartate are probably the neurotransmitters of a majority of mammalian neurons. Only a few previous studies have been concerned with the distribution of the subtypes of EAA receptor binding in the primate brain. We examined NMDA- and quisqualate-sensitive [3H]glutamate binding using quantitative autoradiography in monkey brain (Macaca fascicularis). The two types of binding were differentially distributed. NMDA-sensitive binding was most dense in dentate gyrus of hippocampus, stratum pyramidale of hippocampus, and outer layers of cerebral cortex. Quisqualate-sensitive binding was most dense in dentate gyrus of hippocampus, inner and outer layers of cerebral cortex, and molecular layer of cerebellum. In caudate nucleus and putamen, quisqualate- and NMDA-sensitive binding sites were nearly equal in density. However, in globus pallidus, substantia nigra, and subthalamic nucleus, quisqualate-sensitive binding was several-fold greater than NMDA-sensitive binding. In thalamus, [3H]glutamate binding was generally low for both subtypes of binding except for the anterior ventral, lateral dorsal, and pulvinar nuclei. In the brainstem, low levels of binding were found, and strikingly the red nucleus and pons, which are thought to receive glutamatergic projections, had approximately 1/20 the binding observed in cerebral cortex. These results demonstrate that NMDA- and quisqualate-sensitive [3H]glutamate binding are observed in all regions of primate brain, but that in some regions one subtype predominates over the other. In addition, certain areas thought to receive glutamatergic projections have low levels of both types of binding.     

Digital restoration of indium-111 and iodine-123 SPECT images with optimized Metz filters

A number of radiopharmaceuticals of great current clinical interest for imaging are labeled with radionuclides that emit medium- to high-energy photons either as their primary radiation, or in low abundance in addition to their primary radiation. The imaging characteristics of these radionuclides result in gamma camera image quality that is inferior to that of 99mTc images. Thus, in this investigation 111In and 123I contaminated with approximately 4% 124I were chosen to test the hypothesis that a dramatic improvement in planar and SPECT images may be obtainable with digital image restoration. The count-dependent Metz filter is shown to be able to deconvolve the rapid drop at low spatial frequencies in the imaging system modulation transfer function (MTF) resulting from the acceptance of septal penetration and scatter in the camera window. Use of the Metz filter was found to result in improved spatial resolution as measured by both the full width at half maximum and full width at tenth maximum for both planar and SPECT studies. Two-dimensional, prereconstruction filtering with optimized Metz filters was also determined to improve image contrast, while decreasing the noise level for SPECT studies. A dramatic improvement in image quality was observed with the clinical application of this filter to SPECT imaging.     

Isoquinoline and peripheral-type benzodiazepine binding in gliomas: implications for diagnostic imaging

Binding of the isoquinoline PK 11195 and of the benzodiazepines Ro5-4864 and flunitrazepam was compared in glioma cells and tissues. In human and rat glioma cell cultures [3H]PK 11195 bound with higher affinity (Kd = 14.01 and 15.76 nM, respectively) than either Ro5-4864 (Ki = 1200 and 84.9 nM, respectively) or flunitrazepam (Ki greater than 10,000 and = 848 nM, respectively). Autoradiograms of postmortem human brain sections containing glioma revealed that [3H]PK 11195 bound specifically to intact tumor cells and not to cells of normal cerebral cortex or necrotic areas of the tumor. Total [3H]Ro5-4864 or [3H]flunitrazepam binding to these sections was indistinguishable from nonspecific binding, and regions of tumor and normal brain could not be delineated. These results support the use of radiolabeled PK 11195 for clinical trials of imaging human gliomas by positron emission tomography.     

Assessing stability and change of four performance measures: a longitudinal study evaluating outcome following total hip and knee arthroplasty

Background  

Physical performance measures play an important role in the measurement of outcome in patients undergoing hip and knee arthroplasty. However, many of the commonly used measures lack information on their psychometric properties in this population. The purposes of this study were to examine the reliability and sensitivity to change of the six minute walk test (6MWT), timed up and go test (TUG), stair measure (ST), and a fast self-paced walk test (SPWT) in patients with hip or knee osteoarthritis (OA) who subsequently underwent total joint arthroplasty.     

Using iron deficiency tests for colorectal cancer screening: a feasibility study in one UK general practice

Iron deficiency is common at presentation in colorectal cancer. Testing for it may complement other screening tests such as faecal occult blood testing and sigmoidoscopy. We therefore examined the feasibility of offering iron deficiency testing to patients in a primary care setting in the UK, offering testing to all 1240 patients aged 55-74 years in one general practice in South Wales, UK. Patients with abnormal results were assessed and offered further investigations. Five hundred and fifty-one people (44.4%) attended for iron deficiency blood tests, of whom 26 patients (4.7%) were iron deficient and offered endoscopic assessment. This identified two cases of benign neoplasia amenable to treatment and no cases of cancer. Iron deficiency testing in a screening context appeared feasible although uptake may be low.     

The impact of guidelines on mild hypertension in pregnancy: time series analysis

OBJECTIVE: To determine the impact of a national strategy to promote implementation of a guideline on the management of mild, non-proteinuric hypertension in pregnancy. DESIGN: Simple, interrupted time series analysis. SETTING: Four maternity units in Scotland. POPULATION: Women delivering a live or stillborn baby. METHODS: Dissemination of the guideline under the auspices of a national clinical effectiveness programme, supported by a national launch meeting and feedback from a survey of obstetricians highlighting aspects of care that could be improved. MAIN OUTCOME MEASURES: Appropriateness of initial investigation and subsequent clinical management, and costs of guideline development and implementation activities. DATA COLLECTION: Twenty-four months pre-intervention and 12 months post-intervention data were abstracted from a random sample of case notes. RESULTS: Initial investigation was consistent with recommendations for 59.9% out of 1263 women and subsequent clinical management for 67.6% out of 1081 in whom a diagnosis could be made from available data. There were no significant changes in the appropriateness of initial investigation (10.6%; 95% confidence interval [CI] -0.1% to 19.3%; decreasing by 1.2% per month post-implementation, 95% CI -2.5% to 0.1%) or clinical management (-0.3%; 95% CI -8.7% to 11.2%). Guideline development and implementation cost an estimated pound 2784 per maternity unit in Scotland. CONCLUSIONS: Clinical care of mild hypertension in pregnancy remains highly inconsistent. The lack of the intervention effect may be related to the complexity of the guideline recommendations and the nature of the implementation strategy.     

Specificity of lymphoreticular accumulation of prion protein for variant Creutzfeldt-Jakob disease

BACKGROUND: Immunocytochemical accumulation of prion protein (PrP) in lymphoid tissues is a feature of variant Creutzfeldt-Jakob disease (vCJD) that has been used both to aid in the diagnosis of patients and as a basis of large scale screening studies to assess the prevalence of preclinical disease in the UK. However, the specificity of this approach is unknown. AIM: To assess the specificity of lymphoreticular accumulation of PrP for vCJD by examining a range of human diseases. METHODS: Paraffin wax embedded lymphoreticular tissues from patients with several reactive conditions (58 cases), tumours (27 cases), vCJD (54 cases), and other human prion diseases (56 cases) were assessed. PrP accumulation was assessed by immunocytochemistry using two different monoclonal anti-PrP antibodies and a sensitive detection system. RESULTS: All cases of vCJD showed widespread lymphoreticular accumulation of PrP; however, this was not seen in the other conditions examined. CONCLUSION: Lymphoreticular accumulation of PrP, as assessed by immunocytochemistry, appears to be a highly specific feature of vCJD.