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Biomedical subjects

D Edwards

Publications and source records attributed to D Edwards.

At least 73 records · Page 4Linked to original sources

Trypsin and trypsinogen from an Antarctic fish: molecular basis of cold adaptation.

Trypsin from Antarctic fish Paranotothenia magellanica displays molecular and kinetic properties typical of enzymes produced by psychrophilic organisms. The enzyme has a high catalytic efficiency at low and moderate temperatures and is rapidly inactivated at temperatures higher than 30 degrees C. The nucleotide sequence was determined after mRNA extraction and cDNA synthesis. The cDNA encodes a pretrypsinogen which includes a seven residue activation peptide containing only three acidic residues preceeding the 222 amino-acid mature enzyme. A three-dimensional model of the enzyme was built. Structural parameters possibly involved in the adaptation to cold have been derived from comparison with the three-dimensional structure of the bovine enzyme. Among them are the lack of Tyr-151 in the substrate binding pocket, an overall decrease in the number of salt bridges and hydrophobicity and the increase in the surface hydrophilicity.

Adaptation, Physiological↗

Carpal tunnel surgery outcomes in workers: effect of workers' compensation status.

One hundred thirteen workers' compensation and 53 non-workers' compensation patients who had undergone open carpal tunnel release were queried about job status and the presence or absence of residual symptoms of numbness, pain, or nocturnal awakening an average of 42 months postoperatively. Thirty-nine non-workers' compensation subjects were at their original jobs as compared to only 53 workers' compensation subjects. Seventeen of the workers' compensation subjects were unemployed versus two non-workers' compensation subjects. These differences were significant. Of patients changing jobs, 39 workers' compensation subjects and 2 non-workers' compensation subjects attributed their job change to symptoms of carpal tunnel syndrome. Residual symptoms were significantly more common in workers' compensation compared to non-workers' compensation subjects, with 92 of the former and 26 of the latter subjects reporting some residual symptoms.

Adult↗

Lateral skin flap numbness after total knee arthroplasty.

The authors report the results of a study of lateral skin flap numbness in 25 consecutive primary total knee arthroplasties following the use of a midline, parapatellar incision. All 25 scars were found to have some degree of skin flap numbness, with 24 having an affected skin area of greater than 40 cm2. In two patients (7%), this was considered a significant problem and there appeared to be little improvement with time. The authors therefore feel that lateral skin flap numbness is a significant complication of total knee arthroplasty when a midline, parapatellar incision is used, and patients should be made aware of this complication before surgery.

Aged↗

Magnetic resonance spectroscopy in neonates.

Magnetic resonance spectroscopy allows noninvasive assessment of cerebral metabolism in newborn infants. 31P magnetic resonance spectroscopy has demonstrated that birth asphyxia leads to delayed impairment of cerebral energy metabolism and 1H magnetic resonance spectroscopy has shown lactate accumulation and a later decline in N-acetyl aspartate concentration. 13C magnetic resonance spectroscopy may help explain these observations.

Adult↗

The irritable hip: immediate ultrasound guided aspiration and prevention of hospital admission.

A protocol for the management of irritable hip was assessed; this protocol avoids hospital admission while detecting all other serious causes of hip pain, in particular septic arthritis, at the earliest possible opportunity. Fifty children with painful hips were studied prospectively with immediate ultrasound guided aspiration and Gram stain of all hip effusions. Bone scintigraphy performed at an early stage was reserved for patients with unremitting symptoms. Thirty six hips were aspirated. Only two patients were admitted. The final diagnoses were transient synovitis (45 cases), Perthes' disease (three cases), fracture (one case), and septic arthritis (one case). The single case of hip sepsis was diagnosed on presentation. The traditional approach to management is questioned and the advantages of the protocol highlighted, including earliest diagnosis of sepsis and other serious pathology, avoidance of hospital admission, and the relief of pain by joint decompression.

Ambulatory Care↗

Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.

Biological Transport↗

A guide to strategic planning.

Strategic planning is a new concept in general practice. Underneath all the jargon, however, it is simply a label for the planning and evaluation processes that most organisations have used in the past. The aim of this paper is to demystify strategic planning as it applies to newly formed Divisions of General Practice.

Family Practice↗

Life events and hypertension--a negative finding.

Thirty black Xhosa-speaking unskilled workers, aged between 28 and 59 years, completed three questionnaire measures of stress: Bluen and Odesnik's Township Life Events Scale, Weiman's Occupational Stress Scale and Melamed's Emotional Reactivity Scale. Other variables measured were age, systolic and diastolic blood pressure and body mass index (BMI). Stress levels on all the measures were particularly high in comparison with other groups studied with the same instruments. The well-known relationship between body mass and blood pressure was replicated. However, there was no correlation between blood pressure and any of the stress measures, even when variance in respect of age and body mass was partialled out. It is concluded that the pathways linking stressors to high blood pressure are complex and that caution must be exercised in claiming that there is a link between high levels of urban stress and high incidence of hypertension.

Adult↗

New anti-lung-cancer antibody cluster 12 reacts with human folate receptors present on adenocarcinoma.

Human folate receptor (hFR, folate-binding protein) is a single-chain glycoprotein with high specific affinity for folic acid and methotrexate. We have created 4 monoclonal antibodies (MAbs) to hFR, all of which react specifically with purified hFR in Western blots. Flow cytometry indicated that the antibodies all had patterns of reactivity against epithelial cell lines similar to that of antibody MW207 (workshop antibody 12), labeling 2 breast-tumor cell lines and 2 of 5 SCLC without labeling the one non-small-cell carcinoma tested. We used the antibodies to trace the in situ distribution of hFR in histologically normal tissues and in lung tumors by a sensitive alkaline-phosphatase-anti-alkaline-phosphatase immunohistochemical technique. In frozen sections of normal lung, hFR was diffusely distributed on cell membranes of type-1 and type-2 pneumocytes and mucociliary and basilar respiratory epithelial cells of distal bronchi. The receptor was focally expressed by mucociliary cells of proximal respiratory mucosa and by macrophages, but was not detected in stromal smooth muscle, fibroblasts or lymphoid cells. In tumors, hFR was heavily and diffusely expressed on cell membranes of 9 of 10 pulmonary adenocarcinomas, 5 of 5 bronchioloalveolar carcinomas and 2 of 2 carcinoid tumors. It was focally expressed in 3 of 5 large-cell lung carcinomas and was absent from 4 of 5 small-cell carcinomas, 18 of 22 invasive squamous carcinomas, 2 of 2 in situ squamous carcinomas, and 13 of 13 squamous dysplasias of bronchial mucosa. We conclude that hFR is heavily expressed in situ by normal alveolar and bronchial epithelium and by adenocarcinoma of lung. It is usually absent from small-cell carcinoma and squamous tumors at levels detectable by immunohistochemistry.

Adenocarcinoma↗

Continuous combined and sequential estradiol and norethindrone acetate treatment of postmenopausal women: effect of plasma lipoproteins in a two-year placebo-controlled trial.

OBJECTIVE: Our purpose was to examine the effects of postmenopausal estrogen therapy supplemented with progestogen on plasma lipoprotein levels. STUDY DESIGN: One hundred thirteen women were randomized to receive either placebo or a combination of 17 beta-estradiol and norethindrone acetate administered continuously (Kliogest) or sequentially (Trisequens). Plasma lipoprotein levels were measured at baseline and after 2 years of treatment and compared by analysis of variance. RESULTS: Hormone therapy lowered plasma cholesterol levels (p < 0.001) and low-density lipoprotein cholesterol (Kiogest, p < 0.001; Trisequens, p < 0.01), whereas high-density lipoprotein cholesterol levels were unchanged (Trisequens) or reduced (Kliogest, p < 0.01), primarily because of a decrease in the high-density lipoprotein-2 subfraction (p < 0.05). Low-density lipoprotein/high-density lipoprotein cholesterol ratios remained unchanged. CONCLUSIONS: Although hormonal replacement therapy with estradiol combined with norethindrone acetate eliminated the increase in high-density lipoprotein cholesterol levels observed with estrogen monotherapy, the reductions in low-density lipoprotein cholesterol concentrations still suggest reduced cardiovascular risk, according to the National Cholesterol Education Program and to recent observations indicating that risk is not necessarily inversely proportional to high-density lipoprotein cholesterol levels.

Cholesterol↗

The electrocardiographic effects of cetirizine in normal subjects.

OBJECTIVE: To establish whether the antihistamine cetirizine has the potential to prolong the QTc interval in normal volunteers at up to six times the usual recommended dose. METHODS: Twenty-five healthy volunteers were studied in a prospective, double-blind crossover design conducted on inpatients in a Clinical Research Center. The primary end point of the study was QTc prolongation on the surface electrocardiogram (ECG). Plasma concentrations of cetirizine were also measured for pharmacokinetic analysis. The end point for the pharmacokinetic analysis was the dose/area under the concentration-time curve (apparent clearance of an oral dose). The subjects received the following three treatments in random sequence: placebo, 20 mg/day cetirizine, and 60 mg/day cetirizine for 7 consecutive days. A series of baseline ECGs was recorded over 2 days before each treatment, while the subject receiving placebo. ECG effects of the treatments were then compared with the baseline ECGs. RESULTS: Analysis of variance showed no difference between the treatment groups (placebo, 20 mg cetirizine, and 60 mg cetirizine every day) in effect on QTc compared with baseline. A paired Student t test showed no difference in dose/area under the concentration-time curve between the 20 mg/day and 60 mg/day dosing groups at steady state. CONCLUSION: In healthy volunteers, cetirizine does not prolong the QTc interval at doses of up to six times the usual recommended dose.

Adult↗

Changes in renal angiotensin II receptors in spontaneously hypertensive rats by early treatment with the angiotensin-converting enzyme inhibitor captopril.

We tested the hypothesis that in utero treatment with the angiotensin-converting enzyme inhibitor captopril could change the affinity, density, and/or subtypes of angiotensin II (Ang II) receptors in the kidneys of spontaneously hypertensive rats (SHR). Newborn, 7-day-old, and 4-month-old SHR and Wistar-Kyoto (WKY) rats were used. SHR and WKY rat breeders were treated with captopril (0.4 mg/mL, 100 mg/kg per day) in drinking water, and their pups were maintained on captopril treatment until experimentation. Control groups were untreated, age-matched SHR and WKY rats. The density, affinity, and subtypes of renal Ang II receptors were determined using radioligand binding techniques and receptor antagonists specific for Ang II receptor subtypes 1 and 2 (losartan, an AT1-specific antagonist, and CGP 42112B, an AT2-specific antagonist). AT1 receptor density in kidneys was higher than AT2 receptor density in both neonatal and adult rats. AT1 receptor density in kidneys increased approximately twofold from birth to 7 days of age in all groups. Newborn and 7-day-old SHR showed significantly greater Ang II receptor densities in kidneys than other rat groups because of significantly greater densities of both AT1 and AT2 receptors. At 4 months of age, there were no significant differences in Ang II receptor densities in kidneys between captopril-treated and control SHR. Our data indicate that the expression of AT1 and AT2 receptors in kidneys is differentially regulated during development. Enhanced activity of the renal renin-Ang II system in newborn and probably fetal SHR may be involved in the pathogenesis of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Aspiration or just plain suckers.

Aspiration is one of the most essential services in the dental surgery, for patient comfort, clear vision and assistance with asepsis control, and is imperative during GA/RA procedures for the safety of the patient and for the removal of anaesthetic gases from the working environment. It should be noted that not all vacuum motors are suitable for this application as some brush by-pass motors could present sparking problems if used with these gases.

Gas Scavengers↗

Nonlinear multiple-dose pharmacokinetics of the dopamine reuptake inhibitor vanoxerine.

The human pharmacokinetics of vanoxerine (GBR 12909) were studied in 14 normal subjects with a multiple-dose regimen. In a crossover design, each subject received daily oral doses of 25, 75, and 125 mg for 14 days at each dose level with washout periods of 7 days duration. Drug concentrations in serum during and after dosing were estimated by an HPLC method sensitive to 2 nmol/L (corresponding to 1.04 ng/mL). Drug accumulation was observed during dosing at the two highest dose levels, but near steady-state conditions were attained within 9-11 days of dosing. Estimates of steady-state concentrations all showed statistically significant deviations from dose linearity in the form of disproportionately higher concentrations at higher dose levels than expected from drug concentrations in serum at lower doses. The nonlinear pharmacokinetics was most likely due to increasing bioavailability with dose. The mean elimination half-lives were 53.5 and 66.0 h at 75 and 125 mg/day, respectively, in accordance with the observed time to reach near steady-state conditions. These estimates were higher than previous estimates in less extensive studies.

Adult↗