SIDS. 2. Practical methods for reducing the risk of sudden death.
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Biomedical subjects
Publications and source records attributed to K Jones.
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The Tecumseh project investigates the evolution of hypertension in a healthy population. Of 946 subjects aged 18 through 38 years, 124 had clinic blood pressure readings higher than 140/90 mm Hg (the mean for borderline hypertensive subjects was 130/94 mm Hg). Compared with normotensive subjects, borderline hypertensive subjects had higher home blood pressures (mean, 12/7 mm Hg higher). Their childhood and postpubertal blood pressures were elevated (6/4 mm Hg higher than normal at age 6 years and 12/7 mm Hg higher than normal at age 21 years), and hypertensive target organ changes were detected. Borderline hypertensive subjects also had elevated minimal forearm resistance (0.22 U higher than normal), decreased stroke index (1.8 mL/m2 lower than normal), and impaired ventricular diastolic relaxation (mitral Doppler peak early diastolic blood flow [E] to peak late diastolic blood flow [A] ratio 0.13 lower than normal). Borderline hypertensive subjects had significant abnormalities in other coronary risk factors (cholesterol levels were 0.39 mmol/L higher, triglyceride levels were 0.45 mmol/L higher, high-density lipoprotein levels were 0.08 mmol/L lower, insulin levels were 38 pmol/L higher, and 16.5% more of them were overweight). Borderline hypertension is neither transient nor innocuous. Its association with other predictors of atherosclerosis calls for clinical attention.
The role of protein-tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein-tyrosine kinases. In particular, erbstatin (IC50 approximately 20 micrograms/ml) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 micrograms/ml, genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin.
A double-masked, randomized, placebo-controlled, rising-dose, single-dose study was undertaken to assess the effect of low concentrations of timolol maleate ophthalmic solution (0.008%, 0.025%, 0.08%, and 0.25%) on intraocular pressure and its diurnal variation in healthy, normal volunteers. A single dose of 0.008% timolol exhibits a definite but minimal-effect on intraocular pressure in this normal volunteer model, causing a significant peak mean decrease in intraocular pressure from its value immediately predose. This decrease was 1.8 mm Hg (a peak mean percent decrease of 12.8%) at 2 hours postdose compared with an increase of 0.1 mm Hg (+2.5%) during a pre-study curve due to normal diurnal variation. One drop of 0.008% solution represents a single dose of approximately 2.5 micrograms of timolol. A slight contralateral ocular hypotensive effect appears to be present for 0.25% timolol at 2 hours postdose although it just failed to reach statistical significance.
Focal brain stimulation (FBS) of the periaqueductal gray (PAG) produces reliable antinociception. The use of different electrode configurations alters the distribution of excitation as well as the locus of cells being stimulated, making it difficult to compare results across laboratories. This study compared the analgesic properties of bipolar electrodes delivering biphasic current and monopolar electrodes delivering either a biphasic or a monophasic current to the ventral PAG. Naloxone reversibility of the analgesia was also tested. Results indicate that biphasic current with either monopolar or bipolar electrodes is more likely to elicit analgesia than monophasic current using monopolar electrodes. Naloxone reversed the analgesia produced by the monopolar/monophasic model, but only attenuated the monopolar/biphasic FBS and did not affect the analgesia produced by the bipolar/biphasic configuration. Biphasic current delivered through bipolar electrodes results in the sequential activation of different cell populations. Use of bipolar electrodes may widen the distribution of excitation beyond that of either monopolar configuration. Thus, a wider neural field of excitation may cause a bleedover of the field of stimulation into two systems (one opiate and one nonopiate).
Topographic mapping of brain electrical activity has become a commonly used method in the clinical as well as research laboratory. To enhance analytic power and accuracy, mapping applications often involve statistical paradigms for the detection of abnormality or difference. Because mapping studies involve many measurements and variables, the appearance of a large data dimensionality may be created. If abnormality is sought by statistical mapping procedures and if the many variables are uncorrelated, certain positive findings could be attributable to chance. To protect against this undesirable possibility we advocate the replication of initial findings on independent data sets. Statistical difference attributable to chance will not replicate, whereas real difference will reproduce. Clinical studies must, therefore, provide for repeat measurements and research studies must involve analysis of second populations. Furthermore, Principal Components Analysis can be employed to demonstrate that variables derived from mapping studies are highly intercorrelated and data dimensionality substantially less than the total number of variables initially created. This reduces the likelihood of capitalization on chance. The need to constrain alpha levels is not necessary when dimensionality is low and/or a second data set is available. When only one data set is available in research applications, techniques such as the Bonferroni correction, the "leave-one-out" method, and Descriptive Data Analysis (DDA) are available. These techniques are discussed, clinical and research examples are given, and differences between Exploratory (EDA) and Confirmatory Data Analysis (EDA) are reviewed.
The neurotoxic effects of long-term, low-level exposure to the commercially available insecticide, Fenthion, were examined in the present study. Young (2 month) adult, male Long-Evans rats were dermally exposed to Fenthion (25 mg/kg, 3X week) and sampled after 2 and 10 months exposure to assess neurotoxic damage in the hippocampus using morphological and biochemical endpoints. Histopathology, consisting of gliosis, swollen and necrotic neurons, and cell dropout, occurred in the dentate gyrus (DG), CA4 (hilus), and CA3 sectors as early as 2 months postexposure. Acetylcholinesterase (AChE) staining of brain tissues taken at this time was severely reduced in the septal nuclei, the DG molecular layer, the CA4, and the hippocampus proper. After 10 months exposure to Fenthion, cellular necrosis and gliosis intensified in the CA4 and CA3 regions and occasionally involved the CA2. Radiometric assays of AChE activity in the hippocampus indicated a 65 and 85% depression after 2 and 10 months exposure, respectively. Quinuclidinyl benzilate binding for the hippocampal muscarinic receptor was reduced by 6 and 15%, after 2 and 10 months exposure, respectively. A separate group of older (12 month) rats was exposed to the same dosing regimen of Fenthion and examined for neuropathological damage after 2 and 10 months exposure. Aged animals exposed for only 2 months expressed severe hippocampal degeneration in a pattern similar to that seen in the young adult after 10 months exposure (viz., DG, CA4, CA3). Aged animals exposed for 10 months showed more extensive histopathology of the CA4-2 and occasionally CA1. These observations indicate that in both young adult and aged animals, subchronic, low-level exposure to anticholinesterase compounds can result in serious neurotoxic consequences to the mammalian hippocampus.
Gardner's syndrome is a hereditary disorder characterised by gastrointestinal polyposis, bony osteomata, epidermoid cysts, desmoid tumours and unerupted teeth and odontomes. The major significance of the condition lies in the gastrointestinal polyposis and the high propensity of these polyps to undergo malignant change. The syndrome is no longer considered as a separate genetic entity to familial adenomatous polyposis (FAP) and the multiple stigmata are common to both conditions. A case of Gardner's syndrome is reported and the condition reviewed. The aim being to emphasise those features seen in the head and neck region and their particular importance in terms of early recognition and diagnosis of the underlying disease. The subsequent management of such patients is discussed.
This is a prospective study of aspirin prophylaxis and thromboembolism surveillance in 159 patients having total hip arthroplasty by one surgeon at one institution. All patients had preoperative venous Doppler examination of the lower extremities and a ventilation-perfusion lung scan. Aspirin (650 mg) was given the night prior to surgery and continued at that dose twice per day. Venous Doppler examination was performed 10-14 days after operation. Asymptomatic pulmonary embolism was treated with oral anticoagulation only. There was a 12.6% incidence of pulmonary embolism, but only 1.9% of all patients developed a symptomatic pulmonary embolus. No patient had a fatal pulmonary embolus. No patient had a clinically evident deep vein thrombosis, and venous Doppler examination detected only nine patients with deep vein thrombosis (5.7%). The venous Doppler examination could not predict which patients would develop a pulmonary embolism. The authors could not determine a group of patients at high risk for the development of pulmonary embolism. There was no correlation between well-established "risk factors" and the development of pulmonary embolism. There was no correlation between the use of cemented or uncemented components and the development of pulmonary embolism. There were few complications of this prophylactic regimen of aspirin and surveillance. The authors believe this may be an acceptable prophylactic regimen for patients having total hip arthroplasty. However, the value of venous Doppler examination in the detection of deep vein thrombosis following total hip arthroplasty is uncertain.
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The seasonal variation of thermophilic campylobacters in Lancaster's sewage sludge was studied over a 21 month period. The numbers in fresh sludge (from primary sedimentation) vary between approximately 200 and 5000/100 ml for most of the year but there was a large increase in May and June (in May 1988 there were 42,100 campylobacters/100 ml which is 17 times more than in the preceding April). In 1989 there was a similar May/June peak but with lower numbers. This seasonal variation, measured by environmental monitoring, reflects the incidence of infections in the community. The same pattern was found in 2-d old sludge but the numbers were substantially lower (40% lower over the experimental period). Thermophilic campylobacters were virtually absent from digested sludge and sludge prior to land distribution. Survival experiments confirm that campylobacters survive for only a few hours in both sterile and unsterile digested and undigested sludge. These results suggest that it is safe to dispose of Lancaster's digested sludge on land but there is still uncertainty about the ability of campylobacters to survive in sludge in the viable but non-culturable form.
Environmental monitoring of thermophilic campylobacters in liquid sewage effluent (primary settlement only) during 1988 and 1989 showed a prominent seasonality with distinct peaks in May and June (the average number of bacteria per 100 ml of effluent in months other than May and June was 2244 and the average for the peak months was 50,778). Apart from September 1989, this seasonality coincided precisely with the seasonal variation of campylobacter enteritis in the community with similar distinct peaks in May and June (the incidence of infection in May and June was twice or three times that in the other months). Sampling of sewers showed that the campylobacters in the sewage effluent came mainly from abbatoir and animal processing plants with only a minor input from the community. Therefore, the seasonal peaks in the sewage effluent and in the community may not be dependent on human infections but on zoonotic infections which may also peak in May and June.
The incidence of campylobacter enteritis in Lancaster City Health Authority is three times the UK average for similar sizes of population and has marked seasonal peaks in May and June. Environmental monitoring of surface waters around Lancaster showed that thermophilic campylobacters were absent from drinking water from the fells and from the clean upper reaches of the River Conder but were present in the main rivers entering Morecambe Bay, the lower reaches of the River Conder, the Lancaster canal, and seawater from the Lune estuary and Morecambe Bay. All the surface waters tested showed the same seasonality, namely, higher numbers in the winter months and low numbers or none in May, June and July. The absence of thermophilic campylobacters in the summer months may be due to high sunshine levels because experiments on the effects of light showed that campylobacters in sewage effluent and seawater were eliminated within 60 and 30 min of daylight respectively but survived for 24 h in darkness. As the concentrations of campylobacters in surface waters were at their lowest precisely at the time of peak infections in the community it is unlikely that surface waters form Lancaster's reservoir of campylobacter infection for the community.
Submucous cleft palate is a missed or forgotten diagnosis. We reviewed 81 patients with submucous cleft palate seen over a 15 year period; 26 of these patients were interviewed. The patients were divided into three main groups according to the referral pattern. Children under 2.5 years were referred by a paediatrician for feeding problems; children aged 2.5-10 were referred mainly by speech therapists; and those over 10 had a varied pattern of referral. Thirty nine of the 81 had problems with feeding, but of the 26 interviewed, 22 had feeding problems. Not all patients with a submucous cleft palate are symptomatic and require active treatment, but children with this condition have the same high incidence of middle ear disease as those with overt cleft palate. We suggest that the diagnosis of submucous cleft palate be included in the differential diagnosis of feeding difficulties, with early referral to a specialist cleft palate team.
During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had "white coat" hypertension (i.e., high clinic but not elevated home readings). The prevalence of "sustained" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Bronchoalveolar lavage has been widely used to sample the lower respiratory tract. Most of the material recovered with this technique represents alveolar contents. A number of modifications have been suggested in order to obtain samples relatively enriched for bronchial material. In order to be able to use a standard technique for bronchoalveolar lavage to sample both airways and "routine" alveolar material, a simple modification of the technique as described by Reynolds and Newball was used: five sequential 20-ml aliquots were infused into the lower respiratory tract, and each aliquot was immediately aspirated. The return from the first aliquot was processed separately from the return from the subsequent four aliquots. These last four aliquots were pooled. Analysis of the first aliquot revealed it to be enriched for ciliated epithelial cells when compared with the subsequent aliquots. There were also differences in inflammatory cell composition with the bronchial sample containing relatively more neutrophils and relatively less lymphocytes. Aspiration during transoral bronchoscopy was documented by quantifying salivary amylase in the bronchial and alveolar lavage fluids. It was estimated, however, that the aspiration was not of quantitative significance in the vast majority of subjects studied. Finally, with the technique of fractional processing of bronchoalveolar lavage samples, it was possible to compare the protein concentrations in bronchial and alveolar lavages. Most prominent among the differences was a marked relative enrichment in the bronchial samples for immunoglobulin A. The technique of fractional processing of bronchoalveolar lavage samples provides a simple means to obtain samples enriched for bronchial and alveolar components. This should facilitate analysis of lower respiratory tract specimens in airway disease.