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Biomedical subjects

B McLaughlin

Publications and source records attributed to B McLaughlin.

At least 37 records · Page 2Linked to original sources

Doxazosin in the management of hypertensive diabetes--a cautionary note (?).

Twenty-two patients with diabetes and hypertension were treated with Doxazosin. An acceptable fall in blood pressure was found with 1 mg. in 50% of patients and 2-8 mgs. in 50%. An increase in HDL cholesterol and a fall in LDL cholesterol levels which reached statistical significance was observed. A small but significant increase in HBA1 levels occurred in the 50% of patients on the higher Doxazosin dose.

Antihypertensive Agents↗

Concentrations of endothelial-cell-stimulating angiogenesis factor, a major component of human uterine angiogenesis factor, in human and bovine embryonic tissues and decidua.

Embryonic development involves the establishment of new patterns of vascular growth in the fetus and within the lining of the womb. A factor, human uterine angiogenesis factor, has been purified from the decidua and stimulates the growth of blood vessels in collagen sponge implants and in the chick chorioallantoic membrane. Evidence is presented that suggests that a major active component of human uterine angiogenesis factor is an activator of latent matrix metalloproteinases, of low M(r), called endothelial-cell-stimulating angiogenesis factor and that this factor is present in substantial quantities in a number of embryonic tissues.

Angiogenesis Inducing Agents↗

Detection of incident HIV infection by PCR compared to serology.

In order to determine the most sensitive method for the early detection of HIV infection, polymerase chain reaction (PCR) and serology were compared using matched peripheral blood mononuclear cells (PBMC) and serum samples taken sequentially at 3-month intervals on 17 HIV seroconverters. All samples from the time of enrollment in the study to the time of seroconversion were studied. [There were only two of the 17 cases where PCR and antigen positivity preceded EIA detectable seroconversion.] Initially, one of these cases was found to be PCR positive 11 months prior to seroconversion, however DNA fingerprinting techniques indicated that the early positive specimen did not belong to the subject in question. In a single subject, PCR was negative at the time of serologic evidence of infection but was positive at the next sampling 3 months later. In the remaining 14 cases, PCR was positive at the same sample time as full or partial seroconversion as determined by three EIA screening tests and Western blot. EIA antibody screen tests showed variability in detection of early HIV antibodies. We found no evidence for prolonged HIV infection prior to seroconversion. PCR offers little if any advantage over serology in the early detection of HIV infection in adults.

AIDS Serodiagnosis↗

The Ontario HIV seroprevalence study of childbearing women: results from the first year of testing.

The Ontario HIV Seroprevalence Study of Childbearing Women is an unliked anonymous seroprevalence study designed according to the well-established ethical and legal guidelines for such studies. Commencing in November, 1989, randomly selected neonatal heelprick specimens were tested for the presence of HIV antibodies after all identifying information had been permanently and irrevocably unlinked from the specimens. During the first year of the study 94,119 (approximately 60% of all submitted specimens) were tested. Twenty-six specimens which were repeatedly reactive by EIA were confirmed as positive for an overall crude seroprevalence rate of 2.8 per 10,000 women having live births (95% CI: 1.8-4.1). Twenty-five of the 26 confirmed seropositive results came from babies born in hospitals in the Metropolitan Toronto, Ottawa-Carlton, or Hamilton-Peel-Halton regions.

Adult↗

Activation of the matrix metalloproteinase inhibitor complex by a low molecular weight angiogenic factor.

Tissue inhibitor of matrix metalloproteinases is the major inhibitor of the collagenolytic enzymes and the inhibitory complex has been thought to be irreversible. In this paper we show that a low molecular weight non-protein endothelial cell stimulating angiogenic factor is able to reactivate the enzyme from the inhibitor complex and liberate free inhibitor. The importance of an angiogenic factor able to initiate limited degradation of extra-cellular matrix such that space is created for new capillary growth is discussed.

Angiogenesis Inducing Agents↗

Increased endothelial cell stimulating angiogenesis factor in patients with tibial fractures.

Angiogenesis is an important step in the normal process of fracture healing, irrespective of the method of fixation. Using a quantitative assay, the amount of endothelial cell stimulating factor (ESAF) has been determined in a small group of patients with tibial fractures. ESAF levels were found to be increased when compared with normal volunteers, although this increase was relatively less in fractures held with intramedullary nails than with external fixation.

Adult↗

Detection of Norwalk-like virus and specific antibody by immune-electron microscopy with colloidal gold immune complexes.

Direct electron-microscopy (DEM), immune electron microscopy (IEM) and four different procedures of immune electron microscopy with colloidal gold immune complexes were evaluated for the detection of Norwalk-like virus and specific antibody. A solid-phase immune electron microscopy with colloidal gold immune complexes-triple layer method (SPIEMGIC-TLM) is developed for screening patients' specimens for the detection of Norwalk-like virus and its specific antibody. The method demonstrates low non-specific background labelling and is simple, sensitive and easy to perform. A quadruple layer method (SPIEMGIC-QLM), which is a modification of the triple layer method, has been established by adding a cross-linking anti-IgG layer to amplify the reaction and to provide a more sensitive test which is suitable for screening monoclonal antibodies prepared against 32-34-nm Norwalk-like virus isolated in our laboratory.

Antibodies, Monoclonal↗

Production of endothelial cell stimulating angiogenesis factor (ESAF) by chondrocytes during in vitro cartilage calcification.

The aim of this study was to identify the stimulus for production of the latent collagenase and angiogenic activator ESAF by growth plate chondrocytes. Stimulation correlated most closely with matrix calcification. Alkaline phosphatase was necessary for calcification (and so stimulation of ESAF production) but we could find no evidence for a direct link with ESAF production. ESAF production was also stimulated by addition of preformed mineral to non-calcified cultures but was inhibited by dexamethasone. Protein synthesis was necessary for the stimulation of ESAF production by calcification, though ESAF is not itself a protein. Based on these findings we suggest that chondrocytes, at a suitable stage of maturation in the growth plate, are stimulated to produce ESAF by the proximity of crystals in the matrix. Stimulation, which may consist of the induction of an enzyme or transport protein, leads to the release of this potent activator of collagenolysis as part of the angiogenic cascade.

Alkaline Phosphatase↗

Late onset adrenal hyperplasia in a group of Irish females who presented with hirsutism, irregular menses and/or cystic acne.

The aims of this study were to determine the frequency of late-onset adrenal hyperplasia due specifically to 21-hydroxylase deficiency in a group of Irish women who presented at a Dublin Clinic with symptoms of hyperandrogenism, including hirsutism, menstrual irregularities and/or cystic acne, and to determine if those with 21-hydroxylase deficiency showed particular HLA associations. 119 women had blood samples taken basally and 1 h after an injection of 0.25 mg synacthen with the following hormones profiled: 17-hydroxyprogesterone, 11-deoxycortisol, androstenedione, testosterone, DHEAS and cortisol. Blood sampling was carried out between 0900 and 1000 h during the early follicular phase of the menstrual cycle (when applicable). Ninety-six subjects were new referrals to the Clinic for investigation of hyperandrogenism and 23 were acting as controls. In this study, 6% of patients showed evidence of partial 21-hydroxylase deficiency. In addition, 3 of the 6 with partial 21-hydroxylase deficiency had normal baseline levels of 17-hydroxyprogesterone, with the biochemical abnormality becoming manifest only on synacthen stimulation. Late-onset adrenal hyperplasia due to partial deficiency of this enzyme should always be considered as a possible diagnosis in women who present with symptoms of hyperandrogenism. Synacthen stimulation is an important diagnostic tool in elucidating partial enzyme deficiency as baseline 17-hydroxyprogesterone may be normal in such patients.

Acne Vulgaris↗

Determinants of upper esophageal sphincter pressure in dogs.

Chronic experiments were done on six dogs fitted with EMG electrodes on pharyngeal and esophageal musculature. Electromyographic activity of the cricopharyngeus was recorded in awake and sedated animals with and without manometric recordings as well as during esophageal distension. Intraluminal upper esophageal sphincter (UES) pressure had two distinct components; active contraction accompanied by cricopharyngeal EMG activity and passive elasticity that persisted in the absence of EMG activity. Between swallows, the cricopharyngeal EMG activity patterns observed were of either tonic activity, no activity, or phasic activity with inspiratory bursts. The activity level was markedly affected by anesthesia, phonating, whining, panting, level of alertness, or changes in head posture. A brisk UES contraction was elicited in response to passage of the manometric assembly and to intraesophageal balloon distension. Persistent EMG augmentation after stationing of the manometric sensor suggested that intraluminal manometry tends to exaggerate resting sphincter pressure. We conclude that electrical activity of the cricopharyngeus, and by inference UES pressure, is markedly affected by many variables that are difficult to control during clinical or experimental determinations of UES pressure.

Anesthesia, General↗

Laboratory diagnosis of the first cases of HIV-2 infection in Canada.

Until recently the geographic distribution of infection due to human immunodeficiency virus type 2 (HIV-2) had excluded North America. We report the first two cases of such infection in Canada. Both people came from endemic areas of western Africa and were asymptomatic. The results of a commercial enzyme immunoassay specific for HIV-1 antibody were positive in both cases, but those of the Western blot technique were indeterminate. The Western blot technique specific for HIV-2 antibody and the indirect fluorescent antibody test were used to verify the presence of HIV-2 antibody.

Adult↗

The role of nitric oxide formation in organic nitrate-induced vasodilation and organic nitrate tolerance.

Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 6.2 x 10(-7) M [3H] glyceryl trinitrate (GTN) (9.98 Ci/mmol) in a 30-s time-course study. GTN-induced relaxation of RAS was monitored and tissue GTN and GDN concentrations were determined by thin-layer chromatography and liquid scintillation spectrometry. There was time-dependent biotransformation of GTN to glyceryl dinitrate (GDN) by the RAS and a time-dependent increase in cyclic GMP content in the RAS. Statistically significant (P less than 0.05) biotransformation of GTN and elevation of cyclic GMP content in the tissue were found at 10 s in RAS, whereas the onset of relaxation occurred at 12 s. During the tissue biotransformation of GTN, there was preferential formation of 1,2-GDN compared with 1,3-GDN, suggesting that it is during the process of conversion of GTN to 1,2-GDN that elevation of cyclic GMP content occurs. The results of this study are consistent with the hypothesis that GTN is a prodrug, such that biotransformation to the active metabolite, nitric oxide (NO), is involved in GTN-induced relaxation of vascular smooth muscle. The data also indicate that the mechanism of GTN biotransformation and GTN-induced activation of guanylate cyclase may be related intimately. Isolated RAS were made tolerant to organic nitrates in vitro by incubation with 5 x 10(-4) M GTN for 1 h. After washout and submaximal contraction with PE, the tissues were incubated with 5 x 10(-7) M [14C]GTN for 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The impact of ambulatory glycemic control on the insulin-dependent diabetic gravida.

The pursuit of maternal euglycemia is the cornerstone of contemporary perinatal management of the insulin-requiring diabetic gravida and its achievement has been associated with reduced perinatal morbidity and mortality. The maternal and perinatal results of a pregnancy management protocol for insulin-requiring diabetic gravidas which emphasizes rigorous glucose control via ambulatory patient utilization of reflectance meter determinations of fasting and two-hour postprandial blood glucose is summarized in this report. The authors describe the excellent maternal and neonatal outcomes achieved with this protocol, and emphasize the efficacy of this ambulatory approach to the treatment of insulin-dependent diabetic pregnancies.

Ambulatory Care↗