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Biomedical subjects

D Little

Publications and source records attributed to D Little.

At least 55 records · Page 3Linked to original sources

Comparative assessment of the effect of lomefloxacin, ciprofloxacin, and placebo on cerebral blood flow, and glucose and oxygen metabolism in healthy subjects by positron emission tomography.

The mechanism by which the fluorinated quinolones produce central nervous system (CNS) effects is currently unknown. We measured the effect of lomefloxacin on cerebral blood flow and metabolism using positron emission tomography. Eighteen healthy, nonsmoking volunteers were randomized to receive lomefloxacin 400 mg, ciprofloxacin 750 mg, or placebo given in a single-blind fashion every 12 hours for 72 hours, the time window for maximum lomefloxacin CNS effects. Subjects receiving lomefloxacin had a mean (+/- SEM) cerebral blood flow (CBF) of 46 (2.9) ml/min/100 g, glucose metabolism (FDG) 4.7 (0.4) mg/min/100 g, oxygen metabolism (OM) 3.3 (0.3) ml/min/100 g, and oxygen extraction (%OM) 0.4 (0.04). Posttreatment values were 43 (3.6) ml/min/100 g, 4.2 (0.4) mg/min/100 g, 2.6 (0.3) ml/min/100 g, and 0.4 (0.03), respectively. Values for subjects receiving ciprofloxacin were CBF 44.8 (1.6) ml/min/100 g, FDG 4.9 (0.7) mg/min/100 g, OM 4.1 (0.4) ml/min/100 g, and %OM 0.6 (0.03) at baseline, and 40.3 (3.5), 4.5 (0.6), 3.4 (0.4), and 0.5 (0.09), respectively, after treatment. For placebo-treated subjects, baseline values were CBF 41.4 (1.9) ml/min/100 g, FDG 4.9 (0.5) mg/min/100 g, OM 3.3 (0.4) ml/min/100 g, and %OM 0.5 (0.07), and respective posttreatment values were 42.1 (2.3), 5.0 (0.6), 3.5 (0.3), and 0.5 (0.02). No effect was observed on visual (qualitative), blinded reading of the scans. No significant effect on cerebral blood flow or metabolism was detected. We conclude that short-term administration of lomefloxacin or ciprofloxacin to healthy volunteers does not have a significant effect on cerebral blood flow, or on oxygen or glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Degradation of brain natriuretic peptide by neutral endopeptidase: species specific sites of proteolysis determined by mass spectrometry.

Brain natriuretic peptide (BNP) from 3 different species was cleaved by neutral endopeptidase (NEP) and the products separated by HPLC. The newly formed products were identified by fast atom bombardment or nebulizer-assisted electrospray mass spectrometry to elucidate the sites of proteolysis. Porcine BNP was cleaved at the Arg8-Leu9 and Ser14-Leu15 bonds. Rat BNP was cleaved at the Arg23-Leu24 and Arg30-Leu31 bonds. Human BNP was cleaved at the Pro2-Lys3, Met4-Val5 and Arg17-Leu18 bonds. The Cys-Phe bond which is present in all species of BNP is not cleaved by NEP.

Amino Acid Sequence↗

Comparison of the effect of temafloxacin, ciprofloxacin, or placebo on cerebral blood flow, glucose, and oxygen metabolism in healthy subjects by means of positron emission tomography.

STUDY OBJECTIVE: To determine the cause of the central nervous system effect of the fluorinated quinolones temafloxacin and ciprofloxacin by measuring cerebral blood flow and metabolism by use of positron emission tomography. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. PATIENTS: The patients were 13 healthy, nonsmoking volunteers whose ages ranged from 18 to 40 years. RESULTS: We measured brain blood flow and metabolism by use of positron emission tomography before and after a five-dose course of 750 mg ciprofloxacin, 600 mg temafloxacin, or placebo given every 12 hours. Quinolone administration produced no significant effect on visual (qualitative) reading of the positron emission tomography scans. CONCLUSIONS: We conclude that short-term administration of temafloxacin, ciprofloxacin, or placebo does not significantly alter cerebral glucose or oxygen metabolism. Subjects treated with ciprofloxacin demonstrated a significant decrease in brain blood flow compared with baseline and with temafloxacin- or placebo-treated subjects.

Adolescent↗

The value of Doppler assessment of the uteroplacental circulation in predicting preeclampsia or intrauterine growth retardation.

Flow velocity waveforms of the uteroplacental arteries were analyzed at 20 and 24 weeks of gestation, by means of duplex pulsed Doppler ultrasonography, in 93 women at risk for preeclampsia or intrauterine growth retardation. The ability of an elevated resistance index to predict these conditions was tested. At 20 and 24 weeks an abnormal resistance index was significantly associated with intrauterine growth retardation but not with preeclampsia, with or without proteinuria. A low fetal abdominal circumference at 20 or 24 weeks or an increasing maternal plasma uric acid concentration at 24 weeks was as predictive as an elevated resistance index. In a second group of 43 women, screened in the same way, the only association was of an elevated resistance index at 20 weeks with intrauterine growth retardation. Although elevated resistance indices occur more commonly in women who develop intrauterine growth retardation and/or preeclampsia, the correlation is not close enough to be clinically useful as a screening test.

Blood Flow Velocity↗

Determination of human immunodeficiency virus antibody status in forensic autopsy cases in Vancouver using a recombinant immunoblot assay.

Sera from 207 forensic autopsy cases were tested for the presence of antibody to the human immunodeficiency virus (HIV) using a recombinant immunoblot assay (RIBA) technique developed by Chiron Corporation of Emeryville, California--the Chiron RIBA-HIV216 test system. Out of these cases, 172 autopsies were of individuals with no known risk factors for HIV infection, and of these, 169 had no detectable antibodies to HIV. In 2 cases, the serum reacted with p24 alone on the RIBA-HIV216 assay, but these results were not confirmed by further testing and are considered to be false positive reactions. In 1 case, the serum reacted only with gp41 on the RIBA-HIV216 test but was nonreactive with further testing. This result has been designated equivocal. Of the 35 cases at high risk of HIV infection, 4 had antibodies to HIV detected in postmortem serum samples. The sensitivity (100%) and specificity (98.5%) of the RIBA-HIV216 test system are high. However, the test appears to be more suitable for routine diagnosis of HIV infection than for rapid screening in the mortuary.

Autopsy↗

Affinity purification of endothia protease with a novel renin inhibitor SQ 32,970.

A novel tripeptidic renin inhibitor is described, SQ 32,970, that will potently inhibit endothia protease. This inhibitor can be coupled to Sepharose and will allow the affinity-purification of endothia protease in one step to greater than 95% purity as measured by SDS PAGE. The purified endothia protease cleaves the Lys-Pro-Ala-Glu-Phe-Nph-Arg-Leu substrate at the Phe-Nph bond with a Kcat/Km of 7445 (s-1 mM-1) at pH 3.1 and 4057 (s-1 mM-1) at pH 6.0. Affinity purified endothia protease can be crystallized in the pH range in which it is enzymatically active and can be inhibited by renin inhibitors.

Ascomycota↗

Human lung membrane-bound neutral metallo-endopeptidase-catalyzed hydrolysis of bradykinin.

Human lung membrane-bound neutral metallo-endopeptidase (NME; EC 3.4.24.11) has been purified; this enzyme occurred in two forms, NME-I and NME-II. The total NME activity was purified 2,143-fold with the final specific activities for NME-I and NME-II being 750 and 1,124, respectively. The two NME forms were resolved in the final purification step involving ion exchange; in all earlier steps including gel filtration and affinity chromatography (phenyl sepharose) both forms behaved similarly and eluted simultaneously. NME-I and NME-II both had a Mr value of 97,000, and neither form dissociated into subunits. Catalytic actions of NME-I and NME-II upon bradykinin were identical; the Gly4-Phe5 and Pro7-Phe8 bonds of bradykinin were cleaved with the final hydrolytic products for each enzyme being the tetrapeptide, Arg-Pro-Pro-Gly, the tripeptide, Phe-Ser-Pro, and the dipeptide, Phe-Arg. The intermediate products were the heptapeptide, Arg-Pro-Pro-Gly-Phe-Ser-Pro, and the pentapeptide, Phe-Ser-Pro-Phe-Arg. Neither NME-I nor NME-II were inhibited by the angiotensin-converting enzyme inhibitor, captopril. Both enzymes were inhibited by phosphoramidon, dithiothreitol and EDTA. Other peptidase inhibitors and heavy metals were not effective NME inhibitors. Both NME-I and NME-II cleaved angiotensin-I at the Pro7-Phe8 bond, and substance-P at the Glu6-Phe7 bond, with the latter being much slower than the former.

Amino Acid Sequence↗

In vitro fertilisation in a small unit in the NHS.

In vitro fertilisation is one of the most effective new treatments for infertility, but financial restrictions have made it impossible for it to be widely carried out in the National Health Service. We report on the establishment of a small, largely self funded, unit that was set up with the help of the local health service management. All cycles are programmed so that most work is carried out during the working week; oocyte recoveries are performed as outpatient procedures without general anaesthesia and guided by ultrasound. Roughly a tenth of treatment cycles and roughly a fifth of embryo transfers resulted in a clinical pregnancy.

England↗

Coping and defending styles among Vietnam combat veterans seeking treatment for posttraumatic stress disorder and substance use disorder.

A review of the literature on coping processes in addiction disorders yields at least two notions: one, that substance abuse is associated with less efficient, avoidant ways of coping with problems in living; and two, that substance abusers with a background of traumatic and stressful experiences are readily distinguishable by even more avoidant coping styles. These notions were tested in the form of three hypotheses: (1) substance abusers in general employ more avoidant coping styles than do nonaddicted groups; (2) Vietnam combat veterans meeting DSM-III criteria for both substance use disorder and posttraumatic stress disorder (PTSD) evidence significantly more avoidant coping styles than do Vietnam combat veterans meeting criteria only for substance use disorder but not PTSD--particularly when dealing with internal states of anxiety; and (3) for those meeting both substance use disorder and PTSD criteria, black Vietnam combat veterans (who presumably have encountered more stress, as minority group members) evidence more avoidant coping styles than do white Vietnam combat veterans. These three hypotheses were tested with Peck's (1981) newly developed Individual Styles of Coping, measuring four stages in the coping process for five behavioral contexts. All three hypotheses were confirmed. Results were discussed as confirming recent changes in DSM-III-Revised (1987) criteria, emphasizing generalized avoidance manuevers as criterial, in part, for diagnosing PTSD (in addition to behaviors of specific avoidance of traumatic memories). Theoretical implications about a traumatogenic dimension for substance abuse among some Vietnam combat veterans were discussed, as well as ramifications for treatment programming.

Adult↗

Laboratory study of asthmatic volunteers exposed to nitrogen dioxide and to ambient air pollution.

Adult volunteers with moderate to severe asthma (N = 59) underwent dose-response studies to assess their reactivity to nitrogen dioxide (NO2) in otherwise clean air. Exposure concentrations were 0.0 (control), 0.3 and 0.6 ppm. A subgroup (N = 36) also underwent exposures to Los Angeles area ambient air at times when NO2 pollution was expected. Concentrations of NO2 during ambient exposures were 0.086 +/- 0.024 ppm (mean +/- s.d.). All exposures took place in a movable chamber/laboratory facility. Each study lasted 2 hr, with alternating 10 min periods of exercise (mean ventilation rate 40 L/min) and rest. Lung function was measured prior to exposure and after 10 min, 1 hr and 2 hr of exposure. Symptoms were recorded prior to exposure, during exposure and for 1 week afterward. In some subjects bronchial reactivity to cold air was measured 1 hr after the end of exposure and again 24 hr later. Different exposure conditions were presented in randomized order, 1 week apart. No pollutant exposure produced statistically significant changes in lung function, symptoms, or bronchial reactivity, relative to clean air. Ambient air exposures produced the largest (still nonsignificant) mean changes in some lung function tests. Given the physiological and atmospheric variability, negative statistical results do not rule out a small unfavorable effect of ambient pollution on lung function. If any such effect occurred, it was not likely caused by NO2. Statistical results remained negative when the analysis was restricted to the 20 subjects with most severe lung dysfunction. In conclusion at least in the Los Angeles area, sensitivity to ambient concentrations of NO2 is not common, even among adult asthmatics with moderate to severe disease.

Adult↗

An assessment of the value of biochemical fetoplacental function tests in detecting intrauterine growth retardation.

Four serum biochemical fetoplacental function tests (HPL, unconjugated and total oestriol and AFP) were used to screen for intrauterine growth retardation in 793 patients attending an antenatal clinic. The birthweight corrected for sex, birth ranking and maternal size was used as an index of growth. The sensitivity and specificity of each test was calculated at varying cut-off points and plotted as 'Receiver Operator Curves'. HPL is clearly better than the oestriols or AFP with 80% sensitivity in detecting birth weights of less than the 5th centile when the 25th HPL centile is used as the cut-off point. However, the sensitivity of HPL is sufficiently low to make the value of screening questionable, particularly since 40% of all growth retarded infants were in mothers who did not attend antenatal clinic for screening and 25% of all growth retarded infants were detected by clinical examination.

Female↗

Endothelial cell markers in vascular neoplasms: an immunohistochemical study comparing factor VIII-related antigen, blood group specific antigens, 6-keto-PGF1 alpha, and Ulex europaeus 1 lectin.

Markers for endothelial cells including Ulex europaeus 1 lectin, blood group A, B, and H, and the prostaglandin metabolite 6-keto-PGF1 alpha were evaluated in paraffin secretions from formalin-fixed benign and malignant vascular neoplasms using a variety of immunohistochemical techniques, and results compared with staining for factor VIII-related antigen. Staining for Ulex appeared more sensitive than factor VIII-related antigen in identifying poorly differentiated neoplasms including haemangiosarcomas and spindle cell proliferations in Kaposi's sarcoma. Staining for blood group related antigens correlated with blood group in all cases. Ulex europaeus 1 lectin was the only marker for endothelial cells in lymphangiomas.

6-Ketoprostaglandin F1 alpha↗

Routine ultrasound screening for antenatal detection of intrauterine growth retardation.

This prospective screening program of a large obstetric population was designed to determine the effectiveness of ultrasonic biometry to diagnose intrauterine growth retardation. The results of 3616 pregnancies were analyzed. All pregnancies were dated before the 24th week by ultrasonic measurements. The study compared the effectiveness of three ultrasonic growth parameters: biparietal diameter (BPD), head circumference, and abdominal circumference, to detect intrauterine growth retardation and to determine the optimal gestational age to perform the scan for this purpose. To maintain a high sensitivity required in a screening program, all ultrasonic measurements below the 25th percentile for gestational age were considered abnormal. The predictive value of a positive test in this situation ranged from 0.25 to 0.55, depending on the week of gestation in which the scan was performed. Accuracy of predictions improved greatly when the scans were performed within two weeks of delivery. Abdominal circumference measurements were more predictive of intrauterine growth retardation than either head circumference or BPD measurements or the combination of these parameters. In view of the sensitivity of the test and the prevalence of the disorder, it is concluded that 34 +/- 1 weeks of gestation is the optimal time to screen patients ultrasonically for intrauterine growth retardation.

Abdomen↗

Routine ultrasound screening for the prediction of gestational age.

In a technician-oriented routine ultrasound program, the value of screening an entire obstetric population for predicting gestational age based on a single measurement was evaluated over selective scans performed on the basis of uncertain menstrual history. Consecutive pregnancies of 4527 women were scanned, and the results were analyzed. Gestational ages were determined by both menstrual history and ultrasonic crown-rump length or biparietal diameter (BPD) measurements. The estimated date of confinement based on ultrasound measurements was compared with menstrual history in its ability to predict the actual onset of spontaneous labor. Of patients with optimal menstrual history, 84.7% delivered within +/- two weeks of the date predicted. Only 69.7% delivered within +/- two weeks of the estimate date of confinement based on suspect menstrual history. Crown-rump length measurements were as predictive (84.6%) as optimal menstrual history. Biparietal diameter measurements done between 12 and 18 weeks' gestation were significantly more accurate in gestational predictions (89.4%) than those based on menstrual history (P less than .001). It is concluded that ultrasound cephalometry before 18 weeks is the single best dating parameter.

Cephalometry↗

Fulminant and fatal angioedema caused by bleomycin treatment.

We encountered a case of fulminant and fatal angioedema involving skin and lungs. This reaction, hitherto unreported, occurred 48 hours after termination of a course of bleomycin sulfate. It was not predictable by skin testing, nor was it reversible with steroid therapy. The only predictive clue was the development of eosinophilia during the course of therapy. Fulminant angioedema should be added to the list of potential reactions to bleomycin.

Aged↗

Toward a behavioral assessment of anticipatory symptoms associated with cancer chemotherapy.

A tripartite assessment of nine patients experiencing either pretreatment nausea and vomiting, pretreatment nausea or posttreatment nausea and vomiting only was conducted. Three consistent patterns of response emerged: (1) patients with pretreatment nausea and vomiting reported elevated levels of nausea and anxiety and demonstrated increased levels of physiological arousal; (2) patients with pretreatment nausea reported elevated levels of nausea and anxiety but showed no evidence of increased physiological arousal; and (3) patients with posttreatment symptoms only evidenced low levels on all measures. These data are consistent with the hypothesis that a continuum of responses exists in patients undergoing chemotherapy ranging from no pre- or posttreatment symptoms to pretreatment nausea and vomiting.

Adolescent↗