Biomedical subjects
Publications and source records attributed to P Carr.
1. Whole-blood lactate levels were measured at different rates of haemofiltration in 10 patients with acute renal failure undergoing conventional continuous haemofiltration using lactate-buffered replacement fluid. 2. The results enable both basal production rates and the metabolic clearance of lactate to be estimated in man.
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The structure-activity relationships of bisquinolines, a potentially important group of novel antimalarial drugs, were studied. The high-temperature (180-250 degrees C) synthesis of 4-aminoquinolines, including bisquinolines, by nucleophilic displacement was both fast and efficient Several bisquinolines including (+/-)-trans-N1,N2-bis(7-trifluoroquinolin-4-yl)cyclohexane-1, 2-diamine and 1R,2R-(-)-, 1S,2S-(+)-, (+/-)-trans- and cis-N1, N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamine exhibited potent activity against Plasmodium berghei in mice; (+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1, 2-diamine was orally active. Our results indicate that these compounds conform to a putative receptor for quinoline antimalarials. In addition, a 7-haloquinoline linked by a heterocyclic bridge, at the 4-position, to another heterocycle (such as an acridine at the 9-position) maximally occupies the active site of our postulated target.
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Intracellular pH (pHi) control and relationships between pHi and tension have been investigated in human subcutaneous small arteries. Isometric tension and pHi (using 2',7'-bis(carboxyethyl)- 5(6)-carboxyfluorescein) were estimated simultaneously. pHi recovery from an acute acid load was dependent on external Na+ and partially inhibited by the absence of HCO3(-) [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution] or by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In an HCO3(-)-buffered physiological salt solution (PSS), pHi recovery was partially blocked by hexamethylene amiloride (HMA), an inhibitor of Na+/H+ exchange, and completely blocked by DIDS and HMA together. Intracellular Cl- depletion of arteries did not affect the rate of pHi recovery in PSS from an acid load. pHi recovery from acute alkalosis was unaffected by external Na+ removal, reduced in HEPES buffer, and abolished by removal of external Cl-. These data suggest that human small arteries maintain pHi by Na+/H+ exchange and Na(+)-dependent HCO3(-) exchange in response to an acid load, and Na(+)-independent Cl-/HCO3(-) exchange to counteract intracellular alkalosis. Norepinephrine (NE)-, endothelin-1 (ET-1)-, arginine vasopressin (AVP)-, and K(+)-induced tension did not alter pHi in PSS, but there was a small fall with angiotensin II (ANG II). In HEPES, stimulation with K+, NE, ANG II, or AVP led to a fall in pHi, but this did not occur with ET-1. It is therefore unlikely in vivo that an increase in pHi in these arteries would be involved in either tension development or growth induced by these agonists.
This exploratory study examined the relationship between coping strategies of 136 African-American mothers, their exposure to community violence, and their interpersonal victimization. It is suggested that the disproportionate victimization of African-American women produces a cumulative triple threat for those who live amidst conditions of community violence in the following manner: a) exposure through daily living in the midst of unpredictable community violence; b) exposure to violence from witnessing violence in the neighborhood; and c) exposure to violence from disproportionately high rates of personal victimization. The findings suggest that coping strategies are used differentially as a function of the amount of violence within the social context, and the education and financial resources of the mothers. Mothers who live in lower-violence areas with college education preferred activism as a coping strategy, whereas those in high-violence areas with comparable incomes and education preferred reliance on prayer and instituting safety practices. Coping strategies differed based on whether mothers had been physical victims and witnesses to violence or had no personal experience with violence. This study lays the groundwork for a model of exploring the impact of the cumulative effects of violence on African-American mothers parenting in urban America.
Hypercapnia induces initial constriction and prolonged relaxation of rat small mesenteric arteries. The mechanism of the relaxation is unknown, but has been attributed to lowering of pHi in the vascular smooth muscle. In this study we have investigated the response to raised PCO2 at constant pHo, in mesenteric small arteries precontracted with noradrenaline. 10% CO2 led to a fall in pHi associated with acute potentiation of tension, and subsequent relaxation. The relaxation did not occur in arteries in which the endothelium had been removed, nor in arteries pretreated with the nitric oxide synthase inhibitor, L-NAME (10(-4)M, NG-nitro-L-arginine methyl ester). The D-enantiomer, D-NAME, was without effect. We conclude that hypercapnic-induced vasodilatation in this circulation occurs via endothelium derived nitric oxide production.
A non-invasive assay has been developed for the recovery of r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]-pyrene (BP-7,10/8,9-tetrol) from human urine. This tetrol is excreted as a metabolite of benzo[alpha]pyrene (BP) in a process catalyzed by cytochrome P450 enzymes and epoxide hydrolases. Urine was hydrolysed to release activated benzo[alpha]-pyrene-diol-epoxides covalently bound to macromolecular species or conjugated tetrols. The relatively non-polar organic molecules from urine hydrolysates were collected on octadecasilane chromatography columns (Sep-Paks). Materials eluted in solvent (80% CH3OH), were further purified on immunoaffinity columns with antibodies raised against anti-N2-[10(7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo [alpha]pyrenyl)]-guanosine. HPLC was then used to isolate BP-7,10/8,9-tetrol, which was quantitated by synchronous fluorescence spectroscopy (SFS). This assay detected 0.24-3.12 pmol BP-7,10/8,9-tetrol per ml urine (limit of detection 0.01 pmol/ml, given 10 ml urine), in four study subjects. Reproducibility was assessed by adding tritium labeled BP-7,10/8,9-tetrol (1500 fmol) to a urine sample previously identified to contain the tetrol at levels below the limit of detection of the fluorescence assay; a recovery of > 30% of the added radioactivity was achieved (510 +/- 64 fmol, mean +/- SD, n = 3). Because HPLC alone was not sufficient to isolate materials for quantitation by SFS directly from human urine, immunoaffinity chromatography was found to be a necessary preparatory step in BP-7,10/8,9-tetrol isolation. These data demonstrate the presence of tetrahydrotetrol metabolites of BP in human urine and suggest that measurement of BP-7,10/8,9-tetrol and other polycyclic aromatic hydrocarbon-tetrols may prove to be valuable dosimeters of human internal exposure to polycyclic aromatic hydrocarbons.
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PURPOSE: To examine the choices of career paths of women in internal medicine, specifically to determine (1) whether women continue to prefer primary care practice more often than men do and (2) whether differences in career paths between men and women result from differences in the natures of the training programs they complete. METHOD: A database containing demographic, training, and clinical-practice information on 19,151 physicians (3,569 women and 15,582 men) who had been trained in internal medicine was constructed by merging data from the National Resident Matching Program matches in internal medicine for 1977-1982 with data from the 1985 American Medical Association Physician Masterfile, which contains physician practice profiles. RESULTS: Similar percentages of the men and the women chose primary care residencies (8% versus 9%, ns) and trained in the 100 major medical centers (49% versus 50%, ns). The women more frequently trained in programs affiliated with medical schools in the top prestige quartile (38% versus 33%, p < .05). The attrition rates of residents who left their training for careers in other medical fields were the same for the men and the women (14%). Fewer women obtained board certification (74% versus 80%, p < .01). The women chose to practice general internal medicine more frequently than did the men (52% versus 45%, p < .0001), regardless of the training program completed (primary care or traditional). CONCLUSION: The women pursued primary-care-oriented internal medicine to a significantly greater degree than did the men, regardless of the type of training program completed (primary care or traditional).
The relation between serum lipids, membrane fluidity, insulin, and the activity of the sodium-hydrogen exchanger was investigated in human lymphocytes from 83 subjects. Subjects had a wide range of serum lipids and no concurrent disease. Lymphocyte membrane anisotropy (inversely related to membrane fluidity) was measured with a fluorescence polarization method. Sodium-hydrogen exchange maximal proton efflux rate, affinity for external sodium, and resting pH were determined with the intracellular pH-sensitive fluorochrome 2',5'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Sodium-hydrogen exchange maximal proton efflux rate was negatively correlated with the age of the subject (p = 0.03). Membrane anisotropy correlated with serum triglyceride (p = 0.04). Multiple regression analysis demonstrated that the maximal proton efflux rate in human lymphocytes was significantly related to age (p = 0.005), systolic blood pressure (p = 0.04), membrane anisotropy (p = 0.03), and serum cholesterol (p = 0.03). Incubation of lymphocytes with insulin failed to affect sodium-hydrogen exchange kinetics, intracellular buffering power, or resting intracellular pH. These results suggest that membrane-bound transport proteins may be influenced by serum lipids and the fluidity of the lipid membrane in which they are bound, but they are unlikely to be affected by insulin.
Thallium myocardial defects in patients with no angiographic coronary artery stenosis have been attributed to attenuation effects and other artifacts. Of 323 patients having thallium myocardial imaging following dipyridamole infusion, 10 of 159 patients with a segmental perfusion abnormality were found to have no luminal diameter stenosis greater than 20% on coronary angiography and no electrocardiographic (ECG) evidence of myocardial infarction or left bundle branch block. A time-standardized regional thallium washout ratio was calculated as thallium myocardial counts with dipyridamole to counts without dipyridamole. In comparison to 10 age-matched control patients with no evidence of cardiac disease and no myocardial thallium defect, study patients had a lower regional myocardial thallium washout ratio from both the defect and nondefect (1.57 +/- 0.40 versus 2.27 +/- 0.92, p = 0.041) zones. Nine of the 10 study patients had independent evidence of noncoronary heart disease, including echocardiographic or ECG evidence of left ventricular hypertrophy in six patients. In patients with thallium defects and normal coronary arteriograms, a time-standardized regional thallium myocardial washout ratio for the nondefect zone may aid in the differentiation of patients with noncoronary heart disease from those with soft tissue artifacts.
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