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Biomedical subjects

P Levy

Publications and source records attributed to P Levy.

At least 73 records · Page 4Linked to original sources

Somatostatin in preterm infants: postnatal changes and response to stress.

To determine the chronology of postnatal somatostatin (SRIF) changes in preterm infants and the relationship of SRIF levels to respiratory and gastrointestinal complications, we evaluated sequential SRIF levels in 62 preterm infants in the first month of life. Weekly preprandial plasma samples were obtained and analyzed for SRIF using a radioimmunoassay. Additional blood samples were obtained at the time of abdominal events. Somatostatin levels were highest in week 2 and gradually declined in weeks 3 and 4 (mean +/- SD pmol/l, SRIF = 92.3 +/- 30.3 in week 2 vs. 79.8 +/- 33.9 in week 3 and 69.7 +/- 54.4 in week 4, p < 0.03). Birth weight, gestational age and sex were not related to initial SRIF levels. Infants with respiratory distress requiring assisted ventilation had significantly higher week 1 SRIF levels compared to infants without respiratory problems (97.9 +/- 22.7 vs. 74.9 +/- 21 pmol/l, p < 0.02). Twenty-one of the 62 infants had gastrointestinal complications. Somatostatin levels preceding (89.0 +/- 25.9 pmol/ 1), during (91.0 +/- 13.3) and after (79.3 +/- 28.6) the gastrointestinal events were not significantly different, nor were they different from SRIF concentrations of age-matched preterm infants without gastrointestinal complications. The results suggest that in preterm infants, postnatal SRIF changes follow a definite pattern with peak concentrations in week 2. Respiratory distress is associated with a significant increase in SRIF. However, subsequent gastrointestinal events do not lead to an increase in SRIF. This lack of SRIF response in gastrointestinal stress may play a role in the pathogenesis of gut injury in the premature neonate.

Aging↗

Fractional mercury levels in Brazilian gold refiners and miners.

A field study survey of individuals residing in the region of Para, Brazil, was conducted to determine fractional mercury levels in individuals at risk for exposure in the Brazilian Amazon region. Subjects with a history of exposure to mercury either in the gold mining or refining industry, or exposure to these processes through proximity were included. Three groups were identified as either having recent (less than 2 d since last exposure), intermediate (less than 60 d), or remote (greater than 60 d) exposure to mercury vapors. Fractional blood and urinary mercury levels were assessed for these groups. Group I (recent) had the highest geometric mean blood 24.8 (SD 44.1, range 7.6-158.8) micrograms/L and urine 75.6 (SD 213.4, range 6.5-735.9) micrograms/g-cr (microgram mercury per gram of creatinine) mercury; intermediate (group II) geometric mean blood 7.6 (SD 5.5, range 2.2-19.4) micrograms/L and urine levels 23.8 (SD 84.0, range 7.8-297.0) micrograms/g-cr; the lowest levels in remote exposure (group III): geometric mean blood 5.6 (SD 3.3, range 3.1-14.3) micrograms/L and urine 7.0 (SD 9.8, range 3.1 to 32.9) micrograms/g-cr. The fraction of organic was lowest in group I (32.4%), higher in group II (65.7%), and highest in group III (72.2%). While the frequency of symptoms was comparable in the recent and intermediate groups (2.6 mean, SD 2.3, range 0-8, and 3.1 mean, SD 1.9, range 0-7, symptoms per patient), those with remote exposure demonstrated the highest rate of reporting (6.4 mean, SD 4.1, range 0-11, symptoms per patient). There is significant exposure to mercury for those working in or living near the mining and refining industry. Blood and urine levels are a better marker of recent than remote exposure. The fraction of organic mercury increases with time since exposure. Symptoms may be persistent and low levels of blood and urine mercury do not exclude remote or cumulative toxicity.

Adult↗

[Effects of nicorandil, a potassium agonist, on the human umbilical artery. Role of the vascular endothelium].

The umbilical arteries play an important role in the foetal circulation. These vessels, which have no sympathetic tone, are a valuable model for the study of a direct pharmacological effect on vascular smooth muscle. The aims of this study were to determine if the potassium-channel reopener, nicorandil, could relax the smooth muscle of the human umbilical artery, if glibenclamide, an inhibitor of ATP-dependant potassium channels, can influence the action of nicorandil and, finally, to evaluate the role of the vascular endothelium. Rings of human umbilical artery 3 mm wide were placed in glycosated, oxygenated (95% O2, 5% CO2) Krebs-Henseleit solution, at 37 degrees C, pH 7.4 for isometric myography. The rings were contracted with 10(-5) M 5-hydroxytryptamine (5-HT). After stabilisation, a dose-effect graph of nicorandil (10(-9) to 3 x 10(-4) M) was constructed. In another series of experiments, the rings were incubated with NG nitro-L-arginine (NLA) at 10(-4) M, an inhibitor of NO-synthase, for 15 minutes and then contracted with 5-HT (10(-5) M) and relaxed with nicorandil at the same dosage. In yet another series of experiments, glibenclamide (10(-4) M) was added to the bath 15 minutes before contraction with 5-HT (10(-5) M). The vessel was then relaxed by incremental doses of nicorandil from 10(-9) to 3 x 10(-4) M. During this study, no significant difference was observed with respect to the contractions to 5-HT; moreover, the maximal relaxations obtained by nicorandil before and after glibenclamide were no significant. On the other hand, only the relaxations obtained after incubation with NLA were significant (p < 0.005). Furthermore, the pD2 did not differ significantly between the different groups of vascular rings. The authors conclude that nicorandil is a powerful dilatator of human umbilical artery. Glibenclamide has an inhibitory effect on nicorandil but only at low concentrations and in a non-competitive manner. The endothelium seems to modulate the vascular tone because relaxation is greater in the presence of an inhibitor of NO-synthase: in this type of vessel, the presence of the endothelium predisposes to the liberation of contractile factors.

Antihypertensive Agents↗

Reduced insulin receptor expression and function in human colonic Caco-2 cells by ras and polyoma middle T oncogenes.

Taking advantage of the potent mitogenic effect exerted by insulin in human colonic cells, we used Caco-2 cells transfected with an activated (Val-12) human Haras gene or the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity, to investigate the effect of oncogenic p21ras and PyMT/pp60c-src on insulin mitogenic signaling. As compared to vector control Caco-2 cells, both oncogene-transfected cells exhibited: 1) a loss of response to insulin's stimulatory effect on mitogen-activated protein (MAP) kinase activity and cell proliferation, both of which were constitutively increased; 2) a decrease in insulin receptor (IR) affinity and insulin-stimulated exogenous tyrosine kinase activity, which resulted from increased protein kinase C (PKC) activity (Delage, S., Chastre, E., Empereur, S., Wicek, D., Veissiére, D., Capeau, J., Gespach, C., and Cherqui, G. (1993) Cancer Res. 53, 2762-2770), since IR alterations were corrected by PKC down-regulation; and 3) a decrease in both IR mRNA level and IR number, which was independent of PKC since it persisted after PKC down-regulation. In conclusion, this is the first evidence that oncogenic p21ras and PyMT/pp60c-src abolish insulin mitogenic signaling in human colonic cells through mechanisms involving (i) constitutive activation of MAP kinase and (ii) marked decreases in both IR function and expression which are mediated by PKC-dependent and PKC-independent pathways, respectively.

Antigens, Polyomavirus Transforming↗

Enterocytic differentiation of the human Caco-2 cell line is correlated with down-regulation of fibronectin and laminin.

Human intestinal Caco-2 cells were used to examine the expression of fibronectin (FN) and laminin (LN) during enterocytic differentiation. Combination of immunoprecipitation, Western and Northern blotting revealed that Caco-2 cells expressed a classical FN and a variant form of LN: besides B1 and B2 chains, LN contained a 350-kDa heavy chain instead of the 400-kDa A chain. Throughout Caco-2 cell differentiation, FN and LN synthesis decreased at both mRNA and protein levels. These data indicate that enterocytic differentiation involves both transcriptional and/or post-transcriptional down-regulation of FN and LN gene expression.

Cell Differentiation↗

Motorcycle helmets and spinal injuries: dispelling the myth.

STUDY OBJECTIVE: To determine the relationship between spinal injuries and helmet use in motorcycle trauma. DESIGN: Retrospective case series. SETTING: Twenty-eight hospitals in four midwestern states--Illinois, Iowa, Nebraska and Wisconsin--representing urban, suburban, and rural settings. PATIENTS AND OTHER PARTICIPANTS: Consecutive sample of motorcyclists treated at the participating centers. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The major variables evaluated were helmet use, ethanol use, and significant head or spinal injuries. RESULTS: 1,153 cases were analyzed. Helmet use was not significantly associated with spinal injuries (odds ratio, 1.12; 95% confidence intervals, 0.79, 1.58) whereas head injury was markedly decreased with helmet use (odds ratio, 0.35; 95% confidence intervals, 0.23, 0.53). Ethanol use was a significant variable in both head (odds ratio, 3.89) and spinal (odds ratio, 2.41) injuries. CONCLUSION: In contrast to a significant protective relationship identified for head injuries, helmet use was not associated with an increased or decreased occurrence rate of spinal injuries in motorcycle trauma.

Adult↗

Comparison of lansoprazole with omeprazole on 24-hour intragastric pH, acid secretion and serum gastrin in healthy volunteers.

BACKGROUND: Lansoprazole and omeprazole are proton pump inhibitors which both strongly inhibit acid secretion, resulting in a significant increase in serum gastrin levels. However, no direct comparison of recommended doses (20 mg for omeprazole and 30 mg for lansoprazole) has been reported so far. Our aims were to compare the effects of omeprazole 20 mg/day and lansoprazole 30 mg/day on intragastric acidity and serum gastrin concentration in 12 healthy volunteers. METHODS: The study was double-blind, randomized and placebo-controlled with a cross-over design. On the seventh day of each period, 24-hour intragastric pH was measured using a combined glass electrode placed in the proximal stomach. The last morning dose of each regimen was taken at the end of 24-hour pH monitoring; acid output and serum gastrin concentrations were then studied in the fasting state and after stimulation with pentagastrin (maximal acid output) and a meal (post-prandial gastrin response). RESULTS: Compared to placebo, both drug regimens induced a sustained increase of 24-hour intragastric pH and significantly decreased basal and pentagastrin-stimulated acid secretion. Lansoprazole 30 mg was slightly more effective than omeprazole 20 mg in terms of time spent above pH 3 (P < 0.05). Accordingly postprandial gastrin concentrations rose slightly more after lansoprazole than after omeprazole. All other differences were insignificant. CONCLUSIONS: Both lansoprazole 30 mg and omeprazole 20 mg induce potent and long-lasting acid inhibition, with few minor differences when the two proton pump inhibitors are used at standard doses.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Risk factors for dementia associated with multiple cerebral infarcts. A case-control analysis in predominantly African-American hospital-based patients.

OBJECTIVE: To clarify risk factors for dementia associated with cerebral infarction. DESIGN: Case-control study. SETTING: The study was conducted in a hospital setting. PATIENTS: The subjects were consecutive patients with acute stroke with multiple cerebral infarctions who were admitted to the hospital between November 1, 1987, and December 1, 1990. They were predominantly elderly African Americans. Index cases met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, for multi-infarct dementia, whereas control subjects were patients with multiple infarcts who did not have dementia. There were 61 multi-infarct disease index cases and 86 controls without cognitive impairment. MAIN OUTCOME MEASURES: Demographic and cardiovascular disease risk factor variables. RESULTS: Index cases were older (mean [+/- SD] age, 75.5 +/- 9.7 vs 69.6 +/- 9.1 years), were less well educated (odds ratio, 4.37; confidence interval, 2.12 to 9.04), had lower annual incomes (odds ratio, 8.82; confidence interval, 2.38 to 32.70), more frequently had a family history of dementia (odds ratio, 3.61; confidence interval, 1.09 to 11.96) and laboratory evidence of proteinuria (odds ratio, 3.66; confidence interval, 1.54 to 8.71), had lower scores on neuropsychological tests, had more neurologic signs and symptoms, and were more functionally impaired in activities of daily living. Multiple logistic regression analysis showed that advanced age, lower educational attainment, history of myocardial infarction, and recent cigarette smoking were positively associated with case status and systolic blood pressure level was negatively associated with case status. CONCLUSIONS: Cardiovascular disease risk factors may be modifiable predictors of dementia associated with cerebral infarction. Additional well-designed epidemiologic studies are needed to clarify these associations.

Black or African American↗

Psychopathology associated with Alzheimer's disease and related disorders.

BACKGROUND: This study compared the occurrence of psychiatric symptoms in a large group of community-residing participants enrolled in an Alzheimer's disease patient registry who met clinical diagnostic criteria for Alzheimer's disease or multi-infarct dementia, as well as mixed Alzheimer's disease and multi-infarct dementia. METHODS: Psychiatric morbidity observed from a psychiatric examination of 514 patients with Alzheimer's disease, 135 patients with multi-infarct dementia, and 86 cases with mixed dementia was analyzed using analysis of variance comparing symptoms across groups and chi-square test for differences in frequency of occurrence. Associations between pairs of symptoms were also reported. RESULTS: The frequency of occurrence and patterns of psychiatric problems were similar in patients with Alzheimer's disease and multi-infarct dementia. Agitation was the most frequent symptom, followed by depression, apathy, and behavioral disorders. Patients with mixed dementia had significantly more psychopathology. CONCLUSION: This study demonstrated that significant psychopathology occurs in individuals with Alzheimer's disease or multi-infarct dementia. The high levels of symptoms in mixed dementia suggest that the two conditions have a synergistic effect on behavioral problems. The prevalence of multiple symptoms is higher than previously reported.

Aged↗

Drug use patterns of persons with Alzheimer's disease and related disorders living in the community.

OBJECTIVE: To describe drug use patterns by persons with Alzheimer's disease, multi-infarct dementia, and mixed Alzheimer's disease and multi-infarct dementia. DESIGN: Multicenter, patient registry. SETTING: Community-living persons evaluated in primary care, geriatric, and Alzheimer ambulatory settings. PARTICIPANTS: Of the 930 persons in three diagnostic categories, there were 671 with probable or possible Alzheimer's disease by NINCDS/ADRDA criteria or Alzheimer's disease by DSM-III-R criteria, 162 multi-infarct cases by DSM-III-R criteria, and 97 mixed cases by DSM-III-R criteria. In each diagnostic category, 65% were women, and the majority were 70 years or older. MEASUREMENTS: The average number of all prescription and non-prescription drugs and selected therapeutic categories by age, sex, diagnosis, and mini-mental status score at the time of diagnosis or evaluation. RESULTS: Alzheimer patients average 2.3 drugs compared with multi-infarct (4.3; P < 0.0001) and mixed (3.7; P = 0.002) patients, and their pattern of drug use was different when stratified by therapeutic categories and drug classes. Drug use increased with age, and women used significantly more drugs than men in all three diagnostic categories. Women with Alzheimer's disease used significantly more cardiovascular drugs than men with Alzheimer's disease (P < 0.05). The lower the mini-mental status score in patients with any dementia, the greater the mean number of central nervous system agents used. The higher the mini-mental status score in a patient with multi-infarct or mixed dementia, the greater the use of cardiovascular drugs. CONCLUSION: Drug use by Alzheimer patients was lower than in multi-infarct and mixed patients, primarily due to a lower prevalence of cardiovascular drugs.

Age Factors↗

Muscular metabolism during oxygen supplementation in patients with chronic hypoxemia.

The effects of supplemental oxygen (O2) versus air on working calf muscle metabolism were studied in seven patients with stable chronic obstructive pulmonary disease (COPD) and chronic hypoxemia (PaO2 = 57 +/- 3 SE mm Hg) and seven age-matched control subjects. Oxygen and air were randomly administrated at 24-h intervals, and O2 flow rate was adjusted to correct hypoxemia (PaO2 = 87 +/- 4 mm Hg) in the COPD group. The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined with 31P magnetic resonance spectroscopy at rest, during a graded standardized and localized exercise protocol (360 active plantar flexions), and during recovery. In resting muscle no significant effect of added O2 was demonstrable in each group with regard to pHi, Pi/PCr, and ATP/(PCr+Pi+PME) ratios. Mechanical data were similar between the two groups and between the two tests during the whole exercise. The indices of muscular oxidative metabolism (Pi/PCr and pHi at the end of exercise and recovering PCr resynthesis rate) were impaired in the COPD group compared with that in the control group during air (all p < 0.05). All these parameters were significantly improved with added O2 in the COPD group (p < 0.05), whereas no similar effects were observed in the control group. However, these beneficial effects were incomplete since the exercising Pi/PCr ratio remained higher in the COPD group than in the control group during added O2. This energetic muscular impairment could correspond to tissular damage related to chronic hypoxemia.

Aged↗

Factors predictive of liver histopathological appearance in chronic alcoholic pancreatitis with common bile duct stenosis and increased serum alkaline phosphatase.

In the course of alcoholic chronic pancreatitis, increased serum alkaline phosphatase level is usually caused by common bile duct stenosis but may also be due to alcoholic liver disease. The aims of this prospective study were to investigate whether clinical, biochemical and radiological factors could predict liver histopathological appearance. The study comprised 48 patients with chronic alcoholic pancreatitis, common bile duct stenosis and increased serum alkaline phosphatase levels; clinical, biochemical, radiological and histological data were recorded in all cases. Liver biopsy examination (surgical [n = 45] or intercostal [n = 3]) showed (a) biliary obstructive liver abnormalities (n = 33), which were severe in 20 cases (biliary fibrosis in 15, secondary biliary cirrhosis in 3, secondary sclerosing cholangitis in 2) and moderate in 13 cases; (b) alcoholic liver disease in 9; and (c) normal liver in 6. Clinical, biochemical and radiological data were not statistically different between patients with biliary obstructive liver disease and those with alcoholic liver disease. Forty-five patients underwent surgery; two patients with alcoholic hepatitis died after surgery, at the beginning of this study. We conclude that in chronic alcoholic pancreatitis with common bile duct stenosis and increased serum alkaline phosphatase levels, clinical, biochemical and radiological data cannot be used to predict the type of liver lesions. Therefore liver biopsy is warranted to identify (a) alcoholic hepatitis, which increases operative risk; and (b) biliary obstructive liver disease, frequent and often severe, in which surgical biliary decompression should be considered.

Adult↗

[Contribution of imipenem/cilastatin in the treatment of peritonitis: a comparative economic analysis in the case of France].

Imipeneme, a molecule chemically related to the carbapenems (beta-lactam), is a potent wide spectrum antibiotic reserved for hospital use. Effective as therapy for major infections, and for use in severely debilitated patients (immunodepressed, etc ...) its efficacy in the treatment of peritonitis has been demonstrated in numerous studies abroad, confirmed by results of a French multicenter trial in 1989. Its cost-effectiveness ratio was assessed as excellent in a comparative case-controlled study of totally matched patients treated with other antibiotics. As expected, the cost of the treatment itself (imipeneme/cilastatine plus associated products and costs of their administration) was higher by about 1000 F per patient when compared with other antibiotic regimens, but its markedly superior efficacy allowed overall economies of about four and a half times this sum (4300 F). This cost reduction was related to different factors, some of which could not be individualized because of missing data (personnel) or protocol bias (laboratory examinations). Nevertheless, the global result was a shortening of hospital stay by more than two days due to a very pronounced decrease in failure rate of the first treatment. This result is even more remarkable in that the peritonitis treated by Tienam was significantly more severe than that treated by the other antibiotics.

Anti-Bacterial Agents↗