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Biomedical subjects

M J Nelson

Publications and source records attributed to M J Nelson.

At least 37 records · Page 2Linked to original sources

The platelet function defect of cardiopulmonary bypass.

The use of cardiopulmonary bypass (CPB) during cardiac surgery is associated with a hemostatic defect, the hallmark of which is a markedly prolonged bleeding time. However, the nature of the putative platelet function defect is controversial. In this study, blood was analyzed at 10 time points before, during, and after CPB. We used a whole-blood flow cytometric assay to study platelet surface glycoproteins in (1) peripheral blood, (2) peripheral blood activated in vitro by either phorbol myristate acetate, the thromboxane (TX)A2 analog U46619, or a combination of adenosine diphosphate and epinephrine, and (3) the blood emerging from a bleeding-time wound (shed blood). Activation-dependent changes were detected by monoclonal antibodies directed against the glycoprotein (GP)Ib-IX and GPIIb-IIIa complexes and P-selectin. In addition, we measured plasma glycocalicin (a proteolytic fragment of GPIb) and shed-blood TXB2 (a stable breakdown product of TXA2). In shed blood emerging from a bleeding-time wound, the usual time-dependent increase in platelet surface P-selectin was absent during CPB, but returned to normal within 2 hours. This abnormality paralleled both the CPB-induced prolongation of the bleeding time and a CPB-induced marked reduction in shed-blood TXB2 generation. In contrast, there was no loss of platelet reactivity to in vitro agonists during or after CPB. In peripheral blood, platelet surface P-selectin was negligible at every time point, demonstrating that CPB resulted in a minimal number of circulating degranulated platelets. CPB did not change the platelet surface expression of GPIb in peripheral blood, as determined by the platelet binding of a panel of monoclonal antibodies, ristocetin-induced binding of von Willebrand factor, and a lack of increase in plasma glycocalicin. CPB did not change the platelet surface expression of the GPIIb-IIIa complex in peripheral blood, as determined by the platelet binding of fibrinogen and a panel of monoclonal antibodies. In summary, CPB resulted in (1) markedly deficient platelet reactivity in response to an in vivo wound, (2) normal platelet reactivity in vitro, (3) no loss of the platelet surface GPIb-IX and GPIIb-IIIa complexes, and (4) a minimal number of circulating degranulated platelets. These data suggest that the "platelet function defect" of CPB is not a defect intrinsic to the platelet, but is an extrinsic defect such as an in vivo lack of availability of platelet agonists. The near universal use of heparin during CPB is likely to contribute substantially to this defect via its inhibition of thrombin, the preeminent platelet activator.

Blood Coagulation Disorders↗

Application of the disc angiogenesis system to tumor-induced neovascularization.

Solid tumors elaborate soluble substances that (directly or indirectly) induce angiogenesis by a step-wise process which ultimately results in a microvascular network that nourishes the growing tumor. To study angiogenesis induced by brain tumors we have used a rat glioma model. Modifying the disc angiogenesis system (DAS) we evaluated quantitatively the angiogenic response to cultured, live RT-2 rat glioma cells placed in the center of the discs. DAS were implanted in the subcutaneous tissue of rats and evaluated for vessel proliferation 2 weeks later. Recognition of vessels was greatly facilitated by the staining of their basement membrane using a polyclonal anti-collagen IV antibody. Experimental discs containing 10(3) or 10(5) glioma cells as well as positive control discs containing the agonist prostaglandin E1 consistently demonstrated greater vessel growth than negative controls (discs containing a balanced salt solution). The disc angiogenesis system is a useful tool for the measurement of angiogenic response to living tumor cell suspensions.

Alprostadil↗

A case of gonococcal mastitis in a male.

A case of a 42 year old homosexual man with mastitis of the left breast due to Neisseria gonorrhoeae is presented on account of its extreme rarity. It was probably acquired as a result of direct oral-nipple contact.

Adult↗

Longitudinal prediction of adult blood pressure from juvenile blood pressure levels.

The link between blood pressure measured at juvenile ages (3-18 years) and subsequent adult ages (30 and 50 years) was investigated in a community-based longitudinal study conducted in the San Francisco Bay Area from 1928 to the present. The original sample of 550 persons decreased 61 percent by age 50 years, leaving only 211 persons in the cohort. Blood pressure was measured annually up to age 18 years and each decade thereafter, providing a unique opportunity to link childhood and adult blood pressures over periods of up to 50 years. Juvenile blood pressure measured from age 6 years onward was a positive predictor of blood pressure at age 30 years. Blood pressure measured at age 50 years was predicted best by juvenile pressures measured at early school age and early puberty. The juvenile-adult blood pressure association was partly explained by controlling for smoking and parental history of cardiovascular disease, but was not explained by controlling for juvenile height or body mass. It was stronger in children from blue collar families. The reported correlations probably represent an underestimation of the true strength of the association because of a greater loss to follow-up among subjects with higher blood pressure and the effects of antihypertensive medication in adulthood.

Adolescent↗

Reduction of the active-site iron by potent inhibitors of lipoxygenases.

Lipoxygenases are non-heme iron dioxygenases that catalyze the oxygenation of polyunsaturated fatty acids. Using soybean lipoxygenase-1 as a model, we have shown that two classes of lipoxygenase inhibitors currently in development as potential antiinflammatory agents obtain a significant amount of their potency by reducing the lipoxygenase active-site iron from the active ferric state to the inactive ferrous state. It is not surprising that the members of the first of these classes, the 2-benzyl-1-naphthols, are reducing agents. The members of the second class, the N-alkyl-hydroxamic acids, were not anticipated to be sufficiently strong reducing agents to be oxidized by the lipoxygenase ferric center; that they are provides additional evidence for that iron having a high reduction potential. This brings to (at least) five the number of classes of lipoxygenase inhibitors that are capable of reducing the active-site ferric ion and suggests the generality of this approach in the rational design of lipoxygenase inhibitors.

Binding Sites↗

Heterosexual gonorrhoea in central Sydney: implications for HIV control.

Gonorrhoea is a sexually transmissible disease (STD) characteristic of a core group of individuals and their contacts. From the experience of a Sydney STD clinic, as well as local and national population-based reports, trends in heterosexually acquired gonorrhoea in Australia over a decade were examined. An overall decline of 90% in case numbers between 1981 and 1989 was found, with an average yearly decline of 30%. The improved compliance with condom use by Sydney prostitutes and their clients could have been a major factor. This occurred in an environment of peer and public education about AIDS and the decriminalisation of prostitution. Improved health professional training and public access to specialist STD services against a background of demographic changes may also have contributed. However a persistent "seeding" of penicillinase-producing strains of gonorrhoea from Southeast Asia through men not using condoms was detected. These data have potential implications for the importation of heterosexually acquired human immunodeficiency virus infection into Australia.

Acquired Immunodeficiency Syndrome↗

Vitamin E (tocopherols) in human cerebrospinal fluid.

Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF.

Adult↗

Internal parasite levels and response to anthelmintic treatment by beef cows and calves.

Albendazole (methyl 5-propylthio-1 H-benzimidazol-2-yl carbamate) was used as an anthelmintic in a 3-yr study involving 578 beef cows and 438 nursing calves. Infection levels for nematodes, coccidia, and tapeworm were relatively low throughout the 3-yr period. Eggs per gram of feces in cows and calves were lower (P less than .01) 2 wk posttreatment but were not different 5 mo later, when calves were weaned. Cow weight gain, rate and time of conception, and adjusted calf weaning weights were not affected significantly by deworming of either cows or calves. Level of nematode infection measured as eggs per gram of feces was higher (P less than .01) in younger cows than in mature cows. Although deworming with Albendazole lowered (P less than .01) nematode infection levels, no responses were observed in cow or calf performance.

Age Factors↗

Financial forecasts in healthcare.

Economic forecasts can be a vital tool for management to predict future outcomes and respond to them accordingly. They can also spell trouble for managers who don't know how to properly utilize them. The financial manager must therefore use every tool available when using financial forecasts during the planning process and the author describes the steps necessary in order to make sound judgments.

Decision Support Systems, Management↗

Current therapy of impending myocardial infarction and acute cholecystitis.

The authors discuss the treatment of severe coronary artery disease and acute cholecystitis using laparoscopic laser in one instance and percutaneous transluminal coronary angioplasty (PTCA) in the other. Their report demonstrates that both can be applied with relative safety in close temporal proximity.

Acute Disease↗

Rapid dynamic CT scanning in primary degenerative dementia and age-matched controls.

Dynamic computed tomography (CT) scanning of the brain was performed in 26 patients with primary degenerative dementia (PDD) and in 15 age-matched controls without evidence of a dementing illness. Changes in CT density values over time were obtained for 16 regions of interest (ROIs) that were carefully chosen to avoid overlap with adjacent cerebrospinal fluid (CSF), sulsi, or bone. CT density washout curves were compared between patients and controls to detect regions where blood brain barrier (BBB) permeability might be increased. Although the patients' washout curves declined more gradually than control curves in 11 of the 14 ROIs with a functioning BBB, in no case did the difference reach statistical significance. Intrarater correlation coefficients indicated good overall reliability in the selection of ROIs.

Aged↗

Enzyme-bound pentadienyl and peroxyl radicals in purple lipoxygenase.

Samples of purple lipoxygenase prepared by addition of either 13-hydroperoxy-9,11-octadecadienoic acid or linoleic acid and oxygen to ferric lipoxygenase contain pentadienyl and/or peroxyl radicals. The radicals are identified by the g values and hyperfine splitting parameters of natural abundance and isotopically enriched samples. The line shapes of their EPR spectra suggest the radicals are conformationally constrained when compared to spectra of the same radicals generated in frozen linoleic acid. Further, the EPR spectra are unusually difficult to saturate. The radicals are stable in buffered aqueous solution at 4 degrees C for several minutes. All of this implies that these species are bound to the enzyme, possibly in proximity to the iron. Only peroxyl radical is seen when the purple enzyme is generated with either hydroperoxide or linoleic acid in O2-saturated solutions. Addition of natural abundance hydroperoxide under 17O-enriched O2 leads to the 17O-enriched peroxyl radical, while the opposite labeling results in the natural abundance peroxyl radical, demonstrating the exchange of oxygen. Both radicals are detected in samples of purple lipoxygenase prepared with either linoleic acid or hydroperoxide under air. Addition of the hydroperoxide in the absence of oxygen favors the pentadienyl radical. We propose that addition of either linoleic acid or hydroperoxide to ferric lipoxygenase leads to multiple mechanistically connected enzyme complexes, including those with (hydro)peroxide, peroxide, peroxyl radical, pentadienyl radical, and linoleic acid bound. This hypothesis is essentially identical with the proposed radical mechanism of oxygenation of polyunsaturated fatty acids by lipoxygenase.

Color↗

Infectious diseases of the brain.

Magnetic resonance imaging is the modality of choice for the characterization of intracranial inflammation, by defining ependyma, white matter, gray matter, and leptomeningeal involvement. Hemorrhage is well shown, but calcification is difficult to identify. Intravenous Gd-DTPA is useful in the evaluation of B-b barrier abnormalities. Although it is not often possible to make a specific microbiologic diagnosis, MR appearances are usually helpful in excluding other abnormalities, such as neoplasm or infarction. Knowledge of the number and size of individual lesions is invaluable in monitoring therapy.

AIDS Dementia Complex↗

Preliminary development of a bench-scale treatment system for aerobic degradation of trichloroethylene.

Our results have demonstrated that TCE may be biodegraded to nontoxic products under certain conditions. Trichloroethylene is apparently degraded by strain G4 to CO2, cellular carbon, and inorganic chloride. This activity requires aerobic conditions and exposure of the organism to certain aromatic compounds. This exposure is required to induce the bio-synthesis of one or more enzymes that fortuitously degrade TCE. The normal function of the enzyme(s) is the metabolism of the aromatic compounds. Evidence from the work with environmental samples indicates that the natural microflora in a variety of areas is capable of TCE degradation if stimulated by the appropriate aromatic compounds. These results are presently being applied to the development of bench-scale continuous treatment systems for further assessment of biodegradation as a means for detoxification of TCE-contaminated sites.

Biodegradation, Environmental↗

Infections caused by central venous catheters in patients with acquired immunodeficiency syndrome.

We assessed infectious complications of long-term percutaneous central venous catheterization in patients with acquired immunodeficiency syndrome (AIDS). We evaluated 98 consecutive patients, accounting for 6,298 catheter days. Catheter-associated bacteremia occurred in 3% of patients, a rate of 0.128%/patient-catheter day. Only bacterial pathogens--Pseudomonas, Serratia, and Staphylococcus species--were isolated. Five patients had infection at the catheter exit site. The length of time catheters were indwelling was not significantly different in patients with and those without infections. Percutaneous, multiple-use central venous catheters are safe and well accepted by patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Trichloroethylene metabolism by microorganisms that degrade aromatic compounds.

Trichloroethylene (TCE) was metabolized by the natural microflora of three different environmental water samples when stimulated by the addition of either toluene or phenol. Two different strains of Pseudomonas putida that degrade toluene by a pathway containing a toluene dioxygenase also metabolized TCE. A mutant of one of these strains lacking an active toluene dioxygenase could not degrade TCE, but spontaneous revertants for toluene degradation also regained TCE-degradative ability. The results implicate toluene dioxygenase in TCE metabolism.

Bacteria↗