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Biomedical subjects

P Graf

Publications and source records attributed to P Graf.

At least 73 records · Page 4Linked to original sources

HIV-1 infection as a risk factor for leprosy; a case-control study in Tanzania.

A case-control study was carried out in Tanzania to determine the relative risk of those with HIV-1 infection for getting leprosy. Cases were 93 consecutively diagnosed patients with leprosy aged 15-54 years from the Mwanza Region. Controls were a representative population sample of 4161 people drawn from a stratified cluster sample from urban areas, roadside settlements, and rural villages. HIV-1 infection was determined by enzyme-linked immunosorbent assay (ELISA); Western blot was used when the ELISA result was indeterminate. The HIV-1 prevalence in leprosy cases was 10% in rural (7 of 72) and in roadside and urban areas (2 of 21); in controls these prevalences were 3.4% and 9.9%, respectively. The relative risk of HIV-1 infection for the development of leprosy was estimated to be 2.2 [95% confidence interval (CI) = 1.0-4.7; p = 0.07]. HIV-1 infection was significantly associated with multibacillary (MB) leprosy (odds ratio 4.6; CI = 1.3-13.2) but not with paucibacillary leprosy (odds ratio 1.4; 95% CI = 0.4-3.8). The population etiological fraction for the development of MB leprosy attributable to HIV-1 infection in this population is estimated to be 13% (95% CI = 4%-23%). We conclude that HIV-1 is a risk factor for the development of MB leprosy. The impact of the HIV-1 epidemic on the incidence of leprosy so far has been limited since HIV-1 occurs mainly in urban areas and leprosy in rural areas.

Adolescent↗

Unmasking of the hypotensive effect of nifedipine in normotensives by addition of the angiotensin converting enzyme inhibitor benazepril.

OBJECTIVE: To study the pharmacological interaction between a dihydropyridine derivative (nifedipine slow release 20 mg) and inhibition of the renin-angiotensin system (benazepril 10 mg). DESIGN: Single application at intervals of 2 weeks in an open-label three-way cross-over design. SETTING: Institutional pharmacological unit. PARTICIPANTS: Nine healthy male volunteers. MAIN OUTCOME MEASURES(S): Blood pressure and heart rate were recorded in the supine position for 24 h as well as plasma drug levels, plasma angiotensin converting enzyme activity and active plasma renin concentration. RESULTS: Nifedipine increased active plasma renin two-fold and benazepril increased it five-fold. The combination of the two drugs accelerated the increase of active renin during the first 2 h after drug intake. Whereas no hypertensive effect could be detected after nifedipine or benazepril alone, a significant fall in systolic and diastolic blood pressure was observed for up to 9 to 12 h after the combination. The increase in heart rate induced by nifedipine was minimized by the addition of benazepril. There was no interaction between the pharmacokinetics of benazeprilate and nifedipine which would explain these pharmacodynamic effects. CONCLUSION: These results demonstrate that, in normotensive volunteers, the renin-angiotensin system contributes to mask the hypotensive effect of a single oral dose of dihydropiridine. The concomitant administration of a converting enzyme inhibitor discloses the hypotensive effect and limits the baroreflex-mediated increase in heart rate secondary to vasodilation.

Adult↗

[Morbidity of the donor site of the dorsalis pedis flap].

Detailed information on the dorsalis pedis flap donor-site morbidity is still lacking. In a retrospective analysis, wound-healing, cosmesis, mobility, stability, and thermographic studies of the feet were investigated. The results show a high donor-site morbidity of the dorsalis pedis flap. Indications and alternative methods are discussed.

Adolescent↗

[Defect coverage of the extremities with distal pedicled flap-plasty].

Clinical consideration of anatomy of skin vascularity led to the establishment of distally pedicled flaps in the extremities. In certain situations, distally pedicled flaps are a quick and safe alternative to free microvascular tissue transplantation or distant pedicled flaps. However, an exact indication for this method as well as exact planning and performance of the operation is necessary for success. A synopsis of clinical applications of distally pedicled flaps is given.

Adult↗

Glutathione levels in human lens: regional distribution in different forms of cataract.

The content of glutathione is high in the anterior lens cortex (plus epithelium) and the posterior lens cortex, whereas it is substantially lower in the lens nucleus. A decrease of glutathione in the lens cortex does not occur with lenses from adults up to the highest age. The glutathione content is highest in the cortex of clear fresh lenses and shows a decrease with deep supranuclear cataract, primary nuclear cataract (cataracta brunescens nigra) and clear lenses post-mortem (approximately 20 hr). The subcapsular cataract, especially with additional secondary nuclear cataract, with cataracta matura or intumescens, shows a rapid and pronounced progressive decrease in the glutathione content.

Age Factors↗

Determinants of angiotensin II generation during converting enzyme inhibition.

The reaction of the renin-angiotensin system to acute angiotensin converting enzyme inhibition was investigated in a single-blind, crossover study in nine normal volunteers receiving two out of three regimens in random order: the new converting enzyme inhibitor benazepril (20 mg once or 5 mg four times at 6-hour intervals) or enalapril (20 mg). Plasma converting enzyme activity, drug levels, angiotensin I and angiotensin II, active renin, and aldosterone were measured before and 1-4 hours and 14-30 hours after drug intake. Baseline in vitro plasma converting enzyme activity was 97 +/- 15 nmol/ml/min (mean +/- SD) when Hip-Gly-Gly was used as substrate, but with carbobenzoxy-Phe-His-Leu (Z-Phe-His-Leu) or angiotensin I as substrate it was only 20 +/- 4 and 1.7 +/- 0.3 nmol/ml/min, respectively. Discriminating power at peak converting enzyme inhibition was enhanced with the two latter substrates. In vivo converting enzyme activity was estimated by the plasma angiotensin II/angiotensin I ratio, which correlated well with in vitro converting enzyme activity using Z-Phe-His-Leu as substrate (r = 0.76, n = 252). Angiotensin II levels returned to baseline less than 24 hours after drug administration, whereas in vitro and in vivo converting enzyme activity remained considerably inhibited and active renin together with angiotensin I levels were still elevated. A close linear relation was found between plasma angiotensin II and the angiotensin I/drug level ratio (r = 0.91 for benazeprilat and r = 0.88 for enalaprilat, p less than 0.001). Thus, plasma angiotensin II truly reflects the resetting of the renin-angiotensin system at any degree of converting enzyme inhibition. The ratio of plasma angiotensin II to angiotensin I represents converting enzyme inhibition more accurately than in vitro assays, which vary considerably depending on substrates and assay conditions used.

Angiotensin I↗

[Acute carpal tunnel syndrome and tendon rupture of the long flexor muscle of the thumb as a rare complication of a scaphoid pseudoarthrosis. Case report].

The authors demonstrate a case of a scaphoid pseudarthrosis leading to an attrition rupture of the flexor pollicis longus tendon, tenosynovitis and haemorrhage into the carpal tunnel causing recurrent symptoms of an acute carpal tunnel syndrome. Every acute carpal tunnel syndrome is an emergency requiring instant decompression of the carpal tunnel. If success with conservative treatment of acute carpal tunnel syndrome is questionable, early operative relief of the median nerve is the safest procedure.

Acute Disease↗

Ca2+ mobilization by vasopressin and glucagon in perfused livers. Effect of prior intoxication with bromotrichloromethane.

Perfused livers isolated from rats treated with BrCCl3 for up to 15 min were used as an experimental tool to investigate the role of the hepatic endoplasmic reticulum in Ca2+ mobilization elicited by vasopressin and glucagon. BrCCl3-treatment caused extensive impairment (37 to 92%) of Ca2+ pumps of isolated liver microsomes, while Ca2+ pumps of mitochondria and plasma membrane vesicles remained undamaged. In perfused livers of BrCCl3-treated rats, the efflux of Ca2+ and the concomitant stimulation of O2 consumption and glucose release induced by vasopressin were decreased. The extent of the decrease paralleled the duration of BrCCl3-treatment. The decrease of Ca2+ efflux following vasopressin addition was closely correlated with the decrease of active Ca2+ accumulation by isolated microsomes (r = 0.99, P less than 0.001). The Ca2+ efflux elicited by glucagon was also decreased after BrCCl3-treatment, whereas stimulation of O2 consumption and glucose release were retained. The possibility that BrCCl3-treatment might impair the production of the intracellular Ca2+-mobilizing messenger IP3 is unlikely, since vasopressin still induced the formation of inositol phosphates, including IP3, in isolated hepatocytes obtained from BrCCl3-treated rats. Thus, this work supports the hypothesis that the Ca2+ stored in the liver ER is the major pool of intracellular Ca2+ available for mobilization by vasopressin, glucagon and other effectors.

Animals↗

Modality specificity of implicit memory for new associations.

In previous research we demonstrated that newly acquired associations between unrelated word pairs influence the magnitude of priming effects on word-completion tests. This phenomenon of implicit memory for new associations is observed only following semantic study elaboration. The present experiments reveal that implicit memory for new associations, though elaboration dependent, is also modality specific: Associative effects on a visual word-completion test were consistently reduced by study-test modality shifts. In contrast, explicit memory for new associations, as indexed by cued-recall performance, was uninfluenced by modality shifts. The modality effect on completion performance was eliminated when subjects were given brief visual preexposures to, or were required to construct visual images of, word pairs presented in auditory study conditions. The results pose a theoretical puzzle insofar as they indicate that within the domain of implicit memory, access to the products of elaborative processing depends on modality-specific, sensory-perceptual processing.

Association↗

Assays to measure nanomolar levels of the renin inhibitor CGP 38 560 in plasma.

A radioinhibitor binding assay and an enzyme inhibition assay have been developed to measure plasma levels of CGP 38 560, a potent human renin inhibitor. The detection limit of the assays was between 0.5 and 1 pmol/ml. There was a good correlation (r = 0.989) between the two assays for the measurement of human plasma spiked with CGP 38 560 in concentrations from 1.9 nM to 12 microM. Intra-assay variability was 6.1-17.3% and 4.4-27.2% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Interassay variability was 6.0-28.2% and 3.8-28.4% for the radioinhibitor binding assay and the enzyme inhibition assay, respectively. Blood samples were collected during a pharmacological study performed in normotensive human volunteers on an unrestricted diet who were infused during a 30-minute period with CGP 38 560 A (50 micrograms/kg). Similar values for the concentrations of renin inhibitor in plasma were obtained with the radioinhibitor binding assay and the enzyme inhibitor assay, and there was a significant correlation between values obtained with the two different methodologies (r = 0.94). The plasma levels of renin inhibitor reached a maximum at the end of infusion and then decreased rapidly, indicating a short plasma half-life. The changes in biochemical parameters, plasma renin activity, and plasma concentration of active renin could be related to the concentrations of CGP 38 560 measured in the plasma.

Angiotensin I↗

Hepatic inositol release upon hormonal stimulation of perfused rat liver.

A sustained increase in the hepatic release of 3H radioactivity was shown to occur upon hormonal stimulation of perfused rat liver 15-20 h after intraperitoneal injection of 100 microCi of myo-[2-3H]inositol. Hormone-released radioactive material was analysed by t.l.c. and was found to consist predominantly of [3H]inositol, without further metabolites. Vasopressin (14 nM), phenylephrine (1.7 microM), angiotensin II (15 nM), glucagon (0.5 nM) and dibutyryl cyclic AMP (5 microM) exert maximal effects on hepatic inositol efflux after 10-15 min of stimulation. Omission of Ca2+ from the perfusion medium abolishes the hormone-dependent inositol release. LiCl (10 mM) does not significantly affect the basal release of [3H]inositol, but suppresses vasopressin- and angiotensin-triggered inositol release. Inositol efflux induced by glucagon, dibutyryl cyclic AMP and phenylephrine, however, remains essentially unchanged by LiCl infusion. This establishes a further metabolic difference between these two groups of agonists in that stimuli that act through cyclic AMP produce a stimulated outflow of inositol, but apparently without a Li+-sensitive phosphatase being involved in the overall process.

Angiotensin II↗

Determination of the angiotensin converting enzyme inhibitor benazeprilat in plasma and urine by an enzymic method.

An enzyme inhibition assay for the angiotensin-converting enzyme (ACE) inhibitor benazeprilat is described. Plasma and urine samples were diluted and endogenous ACE was inactivated by heating. After incubation of the plasma samples with hippuryl-histidyl-leucine as substrate and blank plasma as the source of ACE, released hippuric acid was measured by high-performance liquid chromatography. Urine samples were incubated with [3H] hippuryl-glycyl-glycine and with rabbit lung extract as the source of ACE. Released [3H] hippuric acid was quantified by liquid scintillation counting. Drug standards for the standard curve were prepared in the biological matrix. A cross-check with a gas chromatographic-mass spectrometric method showed good agreement, demonstrating that this enzymic method is suitable for assessing drug bioavailability and pharmacokinetics.

Angiotensin-Converting Enzyme Inhibitors↗

Sustained oscillations in extracellular calcium concentrations upon hormonal stimulation of perfused rat liver.

Sustained oscillations in extracellular free Ca2+ were shown to occur on addition of vasopressin, phenylephrine or angiotensin II in isolated rat liver perfused with low (10 microM)-Ca2+ medium. The amplitude and frequency of oscillation depend on hormone concentration. In contrast, Ca2+ releases on addition of ATP, t-butyl hydroperoxide or arachidonate do not exhibit oscillatory behaviour. The vasopressin-induced oscillations were suppressed by glucagon and dibutyryl 3',5'-cyclic AMP, but not by dibutyryl 3',5'-cyclic GMP. These observations in the extracellular space complement observations by Woods, Cuthbertson & Cobbold [(1986) Nature (London) 319, 600-602] on oscillations in intracellular free Ca2+ in single liver cells.

Adenosine Triphosphate↗

Strength and duration of priming effects in normal subjects and amnesic patients.

In three separate experiments, we assessed the strength and duration of word completion effects in amnesic patients and two control groups. In Experiment 1 subjects studied words under a semantic orienting condition and were given tests of word completion and recognition memory after an immediate, 2-hr or 4-day delay. In the word completion test for Experiment 1, we presented three-letter word stems that could be completed to form several common words, one of which had been presented previously (e.g. MOT for MOTEL), and subjects completed each stem with the first word that came to mind. Priming effects were equivalent in amnesic patients and control subjects and they reached baseline levels within 2 hr. In Experiments 2 and 3, subjects studied words under either a semantic or a nonsemantic orienting condition, and word completion was tested at the same three delays using cues that uniquely specified the study words (e.g. JUI for JUICE; or A--A--In for ASSASSIN). In these experiments, amnesic patients exhibited both smaller and shorter lasting word completion effects than control subjects. Specifically, amnesic patients exhibited word completion effects that seldom lasted as long as 2 hr, whereas control subjects usually exhibited completion effects lasting 4 days. An important additional finding was that control subjects exhibited larger and longer-lasting word completion effects when tested under the semantic orienting condition than when tested under the nonsemantic orienting condition. Amnesic patients were not affected by this manipulation. Moreover, under the nonsemantic orienting condition, control subjects and amnesic patients performed similarly. The results show that word completion performance is not always fully intact in amnesic patients. Long-lasting word completion effects found in normal subjects may be mediated by declarative or elaborative retrieval processes, which are impaired in amnesic patients. If so, priming as measured by word completion methods is shorter lasting than recent studies of normal subjects would suggest.

Adult↗

Hormones, glutathione status and protein S-thiolation.

The formation of mixed disulfides between proteins and glutathione has been discussed as a potentially interesting metabolic signal. The S-thiolation of proteins with glutathione has been observed in several systems in vitro. We have correlated the increase in glutathione disulfide (GSSG) with the amount of protein mixed disulfides. The methodological aspects are briefly presented; normal values for protSSG are about 20-30 nmol per g wet weight of liver. Several processes have been related to changes in the thiol redox state. The stimulation of flux through the pentose phosphate pathway during the metabolism of t-butyl hydroperoxide is presented, and the increase in cellular activity of glucose-6-phosphate dehydrogenase is correlated with the increase in the level of protSSG. Hormonal stimulation of GSH efflux from the liver by vasopressin or by alpha-adrenergic agonists such as phenylephrine or epinephrine is presented and discussed in relation to physiological states of peripheral (non hepatic) GSH utilization. Preliminary work relates the release of GSH to the perturbations in thiol redox state in inflammation and in exercise.

Animals↗

Sonography of the hand and foot in foreign body detection.

To evaluate the possibility that sonography might be effective in the clinical detection of foreign bodies in the soft tissues, we used high-resolution sonography to study 10 patients with suspected foreign bodies in the hand and foot. Using ultrasound, we detected foreign bodies (glass, metal wire) in the sole of the foot of two patients and glass in the hand of another. Seven patients were proved to be free of foreign bodies. In an experimental model to ascertain which types of foreign bodies could be detected by ultrasound, wood, glass, and metallic foreign bodies 2.5 cm in length that had been inserted into the flesh of a chicken breast were immediately identified by high-resolution sonography. Ultrasound also pinpointed the surface beneath which the foreign bodies lay and localized all precisely as to depth from the surface. While detection of a foreign body is important, precise localization is crucial to avoid miscalculation of surgery leading to increased tissue damage, blood loss, and an increased risk of complications. This initial study suggests that high-resolution sonography has applicability in both the detection and the precise localization of foreign bodies in the soft tissues, but the sensitivity and specificity of the procedure remains to be determined.

Adult↗