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Biomedical subjects

T J White

Publications and source records attributed to T J White.

At least 73 records · Page 4Linked to original sources

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study.

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.

Aged↗

Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study.

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.

Activities of Daily Living↗

Accelerated evolution of a false-truffle from a mushroom ancestor.

THE false-truffles (Hymenogastrales) are a group of basidomycetous fungi that produce underground truffle-like basidiocarps. They are generally believed to be independently derived from several mushroom lineages, but extensive morphological divergence often obscures recognition of these phylogenetic connections. Comparisons of mitochondrial DNA now demonstrate a surprisingly close relationship between species of false-truffles in the genus Rhizopogon (Hymenogastraceae) and the mushroom genus Suillus (Boletaceae). The striking morphological differences separating all Suillus species from Rhizopogon imply an acceleration in the rate of morphological change relative to molecular change during the evolution of these false-truffles from their mushroom ancestors. This acceleration can best be explained by rapid morphological divergence resulting from selective pressures which may have acted on a small number of developmental genes.

Base Sequence↗

The polymerase chain reaction.

The polymerase chain reaction (PCR) is a powerful new method for 'in vitro cloning'. It can selectively amplify a single molecule of template DNA several millionfold in a few hours and has made possible new approaches to problems in molecular genetics, evolutionary biology, and development.

Biological Evolution↗

Detection of antigens in urine of mice and humans infected with Borrelia burgdorferi, etiologic agent of Lyme disease.

Lyme disease is a seasonal tick-borne malady which has worldwide distribution. Early and accurate diagnosis of Lyme disease is essential for successful antibiotic therapy. Symptoms are too vague to make an early diagnosis based on conventional criteria. We report the detection of antigens of Borrelia burgdorferi, causative agent of Lyme disease, in the urine of infected mice and humans. This technique may eventually provide a rapid diagnostic test for the early and accurate detection of this illness.

Animals↗

Visuwell Reagin, a non-treponemal enzyme-linked immunosorbent assay for the serodiagnosis of syphilis.

A urease-based enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of reagin antibodies in serum. Visuwell Reagin (ADI Diagnostics Inc., Rexdale, Ontario, Canada) is a non-treponemal screening test for the serodiagnosis of syphilis which has the benefits of large batch testing, automatability, and objective interpretation of results. Unheated, undiluted sera are incubated in 96-well microtiter plates coated with a modified cardiolipin-lecithin-cholesterol antigen. Antibody bound to the plate is detected by an anti-human immunoglobulin G-urease conjugate. The procedure consists of three steps, with a total test time of 60 min. Visuwell Reagin ELISA was compared with the Venereal Disease Research Laboratory (VDRL) test and the reagin screening test (RST) with the following results. For ELISA versus the VDRL test, the sensitivities for untreated syphilis (n = 37) were 97.3% for both ELISA and the VDRL test, the confirmatory positive values (n = 79) were 84.8% for ELISA and 72.2% for the VDRL test, and the specificities for normal samples (n = 1,327) were 98.8% for ELISA and 99.5% for the VDRL test. For ELISA versus RST, the sensitivities for untreated syphilis (n = 57) were 94.7% for ELISA and 87.7% for RST, the confirmatory positive values (n = 26) were 96.2% for ELISA and 92.3% for RST, and the specificities for normal samples (n = 1,891) were 99.6% for ELISA and 99.3% for RST. The overall concordance values of ELISA with VDRL test and RST were 96.7 and 97.9%, respectively. The specificity of ELISA compared with that of RST may be underestimated, since confirmatory data were not available for all apparent false-positive samples. Visuwell Reagin had increased sensitivity and similar specificity compared with flocculation tests.

Antibodies↗

Ascaris lumbricoides: zonal localization of immunoreactive collagen in the cuticle.

Monoclonal antibodies that were raised against cuticular components from the free-living nematode Panagrellus silusiae were found to react with a cuticular collagenous domain from Ascaris lumbricoides. One of these monoclonal antibodies was used to localize the collagenous epitope within sectioned Ascaris cuticles. By indirect immunofluorescence, accessible binding sites were observed in the basal zone of the cuticle. Immunological staining occurred in the innermost lamella of the basal zone, i.e., basal lamella, in which the fibrillar palisade gave a strong response. The three layers of the spiral fiber system of the basal zone exhibited a distinctive immunofluorescence pattern. In each of these layers, irregular shaped blocks, often quadrangular, were immunostained; whereas, adjacent blocks were immunonegative. Immunostaining was, for the most part, absent from the cortical and medial zones of the cuticle as well as from other tissues within the worm.

Animals↗

Human CSF-1: gene structure and alternative splicing of mRNA precursors.

Bone marrow progenitor cells differentiate into mononuclear phagocytes in the presence of colony stimulating factor-1 (CSF-1). Characterization of the human CSF-1 gene shows that it contains 10 exons and 9 introns, which span 20 kb. Analysis of multiple CSF-1 transcripts demonstrates that alternate use of exon 6 splice acceptor sites and 3' noncoding sequence exons occurs. These alternatively spliced transcripts can encode either a 224 or a 522 amino acid CSF-1. Implications of differential splicing for the production and function of CSF-1 are discussed.

Amino Acid Sequence↗

A prospective study of 91 patients undergoing both computed tomography and peritoneal lavage following blunt abdominal trauma.

Recent reports comparing computed tomography of the abdomen (CTA) and diagnostic peritoneal lavage (DPL) following trauma have been contradictory. A 10-month prospective study was conducted at our trauma center comparing both methods. Criteria for entry into the study included suspected blunt abdominal trauma without indication for immediate laparotomy, with either equivocal abdominal examination, diminished sensorium, or neurologic deficit. Ninety-one patients meeting these criteria underwent CTA followed by DPL. CTA was performed using both oral and intravenous contrast; DPL was performed by the open technique with RBC greater than 100,000 mm3 or WBC greater than 500 mm3 as criteria for a positive examination. CTA was interpreted initially by available radiology staff and residents and retrospectively reviewed by an experienced tomographer blind to DPL and surgical results. Twenty patients in whom either test was positive underwent laparotomy; all others were admitted for observation and/or extra-abdominal surgery. Laparotomy revealed 26 organs injured in the 20 patients explored at admission; none of the observed patients required delayed laparotomy. The results of CTA and DPL were compared to the findings at laparotomy or the clinical course of those not explored. The sensitivity, specificity, and accuracy for initial CTA were 60%, 100%, and 91%; for review CTA 85%, 100%, and 97%; for DPL 90%, 100%, and 98%. We conclude that: even with experienced examiners, CTA offers no diagnostic advantage over DPL in blunt trauma; because of relative costs, we do not recommend the routine application of CTA; CTA is a reliable alternative when circumstances prevent the performance of DPL.

Abdominal Injuries↗

Pimozide treatment in disruptive severely retarded patients.

Eight severely retarded residents took part in a double blind, placebo controlled trial of pimozide. The drug did not alter behavioural adjustment as assessed by behaviour observations. However, ratings on a standardised checklist of aberrant behaviour showed significant drug-induced improvements on two dimensions (Irritability and Hyperactivity/non-compliance). Learning performance, as assessed by a discrimination learning task, was not affected by the drug.

Adolescent↗

Pelvic extramedullary hematopoiesis.

Extramedullary hematopoiesis is an infrequent cause of thoracic masses. Extrathoracic locations are even less common. We have studied two patients, one with suspected pelvic neoplasm, with technetium-99m sulfur colloid marrow image and transmission computerized tomography. This noninvasive evaluation established the diagnosis of pelvic extramedullary hematopoiesis in both. We recommend a similar diagnostic approach in patients with chronic anemia or other predisposing disease, presenting with a pelvic or abdominal mass.

Adult↗

Anilides related to substituted benzamides. Potential antipsychotic activity of N-(4-amino-5-chloro-2-methoxyphenyl)-1-(phenylmethyl)-4-piperidinecarboxamide.

The substituted benzamides are used clinically both as antipsychotics and as stimulants of gastric motility. The antipsychotic effects are considered to be a consequence of their central dopamine antagonist properties, but there is evidence that the gastric stimulatory effects may be mediated by other mechanisms. Clebopride (3) is a substituted benzamide that although marketed for its stimulatory effects on gastric motility, is also a potent central dopamine antagonist. The corresponding anilide, BRL 20596 (4a), where the amide bond has been reversed, has been synthesized and found to lack gastric stimulatory activity. However, the potent central dopamine antagonist activity is retained, suggesting that benzamides and anilides have similar affinities for central dopamine receptors. The implications of the conformations adopted by benzamides and anilides at such receptors are discussed. Evidence is also presented that there is a further lipophilic binding site on such receptors for which the N-benzyl group is an optimal fit.

Animals↗

Pulmonary artery occlusion due to histoplasmosis.

Histoplasma mediastinitis with complete or partial pulmonary artery obstruction due to compression and/or intraluminal granuloma was diagnosed in five patients and surgically verified in two. The patients, ages 12-27 years, had cough, dyspnea (four cases), and hemoptysis (two cases). Radionuclide imaging showed unilateral absence of pulmonary perfusion and minimal diminution of ventilation. Differentiation of this inflammatory process from other causes of ventilation-perfusion mismatch, for example, congenital hypoplasia and certain acquired causes of arterial obstruction, especially thromboembolism, may be possible by correlating radiographs, laminograms, and clinical history. Angiography can delineate the extent of perfusion impairment and may suggest its cause.

Adolescent↗

Computed tomography of jugulotympanic paragangliomas.

Seven cases of jugulotympanic paragangliomas were studied with computed tomography (CT) and verified by angiography and surgery. All of five glomus jugulare tumors were detected and their extent accurately demonstrated by CT. Two small glomus tympanicum tumors were not convincingly demonstrated. Computed tomography is useful in investigating this neoplasm when it extends beyond the tympanic cavity or is associated with bone destruction.

Aged↗