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Biomedical subjects

M Stevens

Publications and source records attributed to M Stevens.

At least 127 records · Page 7Linked to original sources

Immunoquantification of cytochrome P-450 3A on rat paraffin-embedded liver tissue.

The cytochrome P-450 3A family is involved in the metabolism of several drugs, including nifedipine, cyclosporine, quinidine and erythromycin. The purpose of this study was to develop a reliable method to obtain a relative quantification of cytochrome P-450 3A apoproteins in rat liver specimens by immunocytochemistry and to correlate such quantification to erythromycin N-demethylase activity, a biochemical pathway sustained by that enzymatic system. Thirty-six male Wistar rats were treated with an injection of either saline or dexamethasone phosphate (10, 30 or 50 mg/kg), a potent inducer of cytochrome P-450 3A. Specimens taken from the same lobe were processed for immunocytochemistry and determination of erythromycin N-demethylase activity. Paraffin sections were treated with a polyclonal antiserum directed against cytochrome P-450 3A. The density of cytochrome P-450 3A immunostaining measured by an automatic image analyzer increased with the dose of dexamethasone pretreatment, and with the erythromycin N-demethylase activity, both parameters being closely correlated. Our data indicate that in rats, when cytochrome P-450 3A is concerned, there is a close correlation between the results of immunoquantitation and biochemical activity. This suggests that such a method of investigation might be used on small paraffin-embedded liver specimens obtained by needle biopsy.

Animals↗

Comparison of Sentinel and Bactec blood culture systems.

AIMS: To evaluate the Sentinel automated blood culture system and to compare its performance with that of Bactec. METHODS: The Sentinel blood culture system was evaluated in three centres. The performance of the system was assessed in comparison with the routine blood culture method used in these centres, the Bactec system. RESULTS: Blood culture sets (n = 2180) consisting of Sentinel aerobic and anaerobic, and Bactec aerobic and anaerobic bottles yielded 218 (10%) clinically important isolates. One hundred and fifty five (71%) of the isolates were detected by both systems; 35 (16%) were detected by Sentinel only; and 28 (13%) by Bactec only. For the duration of the evaluation, the Sentinel system was deliberately configured so that it was impossible to detect positive results during the first 12 hours. The times to positivity after the first 12 hours were similar. Data gathered during and subsequent to the evaluation have been used by the manufacturer to refine the algorithm so that positive results can be detected at a minimum of 2.25 hours. CONCLUSIONS: After a period of familiarization the Sentinel system was considered easy to use. Sentinel is a useful addition to the methods available for the detection of bacteria in blood cultures.

Bacteriological Techniques↗

Drug screening of newborns by meconium analysis: a large-scale, prospective, epidemiologic study.

A large-scale, prospective drug screening of newborns by meconium analysis was done to determine more accurately the prevalence and epidemiologic characteristics of drug use in a high-risk urban, obstetric population. Every other neonate delivered in a perinatal center from November 1988 to September 1989 was prospectively enrolled and their meconium was analyzed by radioimmunoassay for the metabolites of three commonly abused drugs--cocaine, morphine (opiates), and cannabinoid. In 3010 subjects studied, 44% were positive for cocaine, morphine, or cannabinoid; 31% were positive for cocaine, 21% for morphine, and 12% for cannabinoid. In contrast, only 335 (11%) mothers admitted to illicit drug use: 52% of their newborns had a positive urine drug screen and 88% had a positive meconium drug screen. Prevalence of drug use among the pregnant women varied per month. A profile of the pregnant addict in the population studied was noted (P less than .001): service patient, single, multigravid (greater than 3), and little or no prenatal care. The major problems associated with drug use during pregnancy were principally noted in the group that was exposed to cocaine and opiates and in the group where the mothers admitted to the use of illicit drugs. On the other hand, a large number of neonates who have been exposed to drugs in utero, particularly those whose mothers denied the use of drugs, appear normal at birth and may not be recognized. Improved detection of these newborns at risk can be achieved with a high index of suspicion and meconium drug analysis.

Cannabis↗

Falsely raised ankle/brachial pressure index: a method to determine tibial artery compressibility.

The ankle/brachial index (abPI) may be falsely raised, notably in diabetes, due to the relative incompressibility of the tibial artery. This paper presents a method of determining tibial artery compressibility by deriving abPIs with the patient supine and with legs raised in increments up to 0.55 m (ankle to heart). The effective negative hydrostatic pressure superimposed on the blood pressure at the ankle was converted to mmHg, normalised with respect to the brachial systolic pressure and then expressed as a hydrostatic pressure index (hPI). abPI was regressed on hPI and the gradient of the regression line calculated. If the arterial wall offers no significant resistance to compression the measured pressure will equal intraluminal pressure. In this case regression of the changing arterial pressure with the applied hydrostatic pressure would be expected to produce a gradient of -1. With resistance to compression the measured pressure is greater than the intraluminal pressure and a steeper gradient would be expected. The method was tested using age and sex matched groups, (A) controls (16 arteries), (B) patients with PVD and no diabetes (17 arteries), and (C) diabetics with PVD (34 arteries). There was no significant difference between the regression line gradients of groups A and B but both differ significantly from group C. The difference between the medians of groups B and C was 0.46, the 95% confidence interval for the difference being 0.66 to 0.02. Twelve of the diabetic arteries had a gradient steeper than -1.8 compared with one from group (B) and none from group (C).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cord serum IgE: an insensitive method for prediction of atopy.

Cord total serum IgE has been advocated as a screening test to detect infants at high risk of allergy who would be suitable for preventive measures. In a population based prospective study to look at the predictive capacity of cord IgE and family history of atopy 1111 one-year-old infants were followed-up. Cord IgE was measured using the EIA ultra technique (Pharmacia, Uppsala, Sweden). Atopic symptoms developed in 255 (23%) at one year, 183 (16.5%) had probable atopy (clinical disorder but negative skin prick test (SPT)) and 72 (6.5%) had definite atopy (clinical disorder with positive SPT). There was no difference in the mean cord IgE levels in infants with or without atopic manifestations. The cut-off for IgE was taken at 0.6 ku/1. The specificity of the test was 92% but the sensitivity was only 8.5%. The positive and negative predictive values were 24% and 78% respectively. Family history of atopy is far more sensitive in detecting infants at risk of atopy and little is added by knowledge of cord IgE.

Asthma↗

A controlled trial of colchicine to reduce the elastase load in the lungs of ex-cigarette smokers with chronic obstructive pulmonary disease.

A great deal of experimental evidence suggests that emphysema in smokers is caused by the action of neutrophil elastase on lung elastin. In order to test this hypothesis, it is necessary to find a drug that reduces the load of neutrophil elastase in the lungs of patients with emphysema. In a previous study we treated smokers with emphysema with colchicine, a drug that prevents neutrophil elastase secretion, to determine if it would reduce the elastase burden in the lungs. Colchicine was unable to reduce the elastase load while the stimulus of smoking continued. In this study we treated ex-smokers with emphysema to determine if colchicine could reduce the elastase burden in the lungs. The objective of the study was to determine if colchicine can reduce the elastase load and putative indicators of elastase load in the lungs of patients with chronic obstructive pulmonary disease. The study was a prospective, double-blind, randomized, and placebo-controlled clinical trial. The subjects were outpatients seeking treatment at the University of Texas Health Center at Tyler. We studied 16 ex-cigarette smokers between 45 and 75 yr of age with lung disease defined by FEV1 less than 70% of predicted but greater than 1.2 L whose airflow obstruction was less than 20% reversible with bronchodilators. Colchicine or placebo was taken by mouth in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of theodur by mouth and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Prevalence and correlates of alcohol use in a survey of rural elementary school students: the New Hampshire study.

Alcohol use by 1190 fourth, fifth and sixth grade students was assessed in a survey of four rural New Hampshire school districts. Half the students surveyed (596) drank, but not regularly; 5 percent (59) were regular drinkers, and an additional 2 percent (19) were regular drinkers and had been drunk at least once. Reported alcohol use increased with both grade and age, and males drank more than females. The child's attitude toward drinking, perceived family attitudes towards drinking, the number of drinking friends, and self-perceived wrongdoing by the child were four factors strongly related to alcohol use. Increased alcohol use was also associated with experimental and current use of cigarettes, marijuana, and smokeless tobacco.

Adolescent↗

Detection of Staphylococcus aureus in blood cultures: evaluation of a two-hour method.

Aurease--one of three tests on the RAPIDEC staph system for two-hour identification of the main clinically important staphylococci--was used for the direct detection of Staphylococcus aureus from 102 blood culture broths in which Gram-positive cocci were seen. A pellet of centrifuged blood culture broth was used as the inoculum. The method was compared with the thermonuclease test and subsequent isolates subjected to probabilistic identification based on biochemical reactions. A positive aurease test and the presence of thermonuclease were detected in 27 samples, subsequent identification showing all to be Staph. aureus. A further Staph. aureus strain was aurease negative but thermonuclease positive. None of the remaining 74 specimens was positive by the aurease test, which is rapid, sensitive and specific for detection of Staph. aureus in blood culture broths.

Bacteriological Techniques↗

A rapid test to detect the most clinically significant Staphylococcus species.

A new two-hour test system (RAPIDEC staph) to detect the main staphylococci was evaluated. Of 124 reference strains tested, 83 represented species most often found in clinical specimens, the remaining 41 strains representing five species primarily of animal origin. RAPIDEC staph detected all Staph, aureus, Staph. epidermidis and seven of eight Staph. saprophyticus strains. Of the animal species, all Staphylococcus intermedius strains were assigned to the correct category, the remainder were misidentified as Staph. epidermidis. With 121 catalase-positive Gram-positive cocci isolated from urines the test system correctly detected all Staph. aureus strains, 39 of 41 Staph. epidermidis, and 34 of 36 Staph. saprophyticus. Of 25 atypical Staph. aureus strains which were either slide or tube coagulase negative the test system correctly detected all 17 slide coagulase negative strains but failed to detect eight which were tube coagulase negative. There were no false positives. RAPIDEC staph is a rapid, accurate system for the detection of the three main clinically important species of staphylococci.

Bacteriological Techniques↗

Neurohypophyseal hormones and excessive grooming behaviour.

The pattern of excessive grooming displayed by rats treated with vasopressin and oxytocin was investigated by calculating the frequencies and contribution of the behavioural elements head washing, body grooming, anogenital grooming, paw licking and scratching. In addition, the suppressive effect on peptide-induced grooming of the dopamine D1 receptor antagonist SCH 23390, of neurotensin and of the opiate receptor antagonists naloxone and naloxone-methobromide was studied. The pattern of excessive grooming induced by vasopressin and by oxytocin was characterized by the contribution of most behavioural elements to the total grooming scores. Oxytocin-induced excessive grooming was characterized by a marked increase in the frequency of anogenital grooming. SCH 23390, neurotensin and naloxone, but not naloxone-methobromide, suppressed excessive grooming induced by vasopressin and oxytocin. It is suggested that dopamine D1 receptors as well as opiate receptors located within the blood-brain barrier are involved in the excessive grooming induced by neurhypophyseal hormones.

Animals↗

Mouse plasmacytoma growth in vivo: enhancement by interleukin 6 (IL-6) and inhibition by antibodies directed against IL-6 or its receptor.

Murine plasmacytomas show a striking dependence on interleukin 6 (IL-6) for their growth in vitro. Here, we present evidence suggesting that IL-6 also plays an essential role in the in vivo development of these tumors. This conclusion is based on the finding that the tumorigenicity of an IL-6-dependent plasmacytoma cell line was increased approximately 100-fold on transfection with an IL-6 expression vector, whereas it was inhibited in animals treated with monoclonal antibodies capable of blocking the binding of IL-6 to its receptor. Injection of these antibodies 1 d before tumor challenge protected greater than 50% of the mice and retarded tumor growth in all animals. Tumors arising in antibody-treated mice retained their IL-6 dependence in vitro, suggesting that the level of protection could be improved if stronger IL-6 antagonists were available.

Animals↗

Actinobacillus rossii sp. nov., Actinobacillus seminis sp. nov., nom. rev., Pasteurella bettii sp. nov., Pasteurella lymphangitidis sp. nov., Pasteurella mairi sp. nov., and Pasteurella trehalosi sp. nov.

Evidence from numerical taxonomic analysis and DNA-DNA hybridization supports the proposal of new species in the genera Actinobacillus and Pasteurella. The following new species are proposed: Actinobacillus rossii sp. nov., from the vaginas of postparturient sows; Actinobacillus seminis sp. nov., nom. rev., associated with epididymitis of sheep; Pasteurella bettii sp. nov., associated with human Bartholin gland abscess and finger infections; Pasteurella lymphangitidis sp. nov. (the BLG group), which causes bovine lymphangitis; Pasteurella mairi sp. nov., which causes abortion in sows; and Pasteurella trehalosi sp. nov., formerly biovar T of Pasteurella haemolytica, which causes septicemia in older lambs.

Abscess↗

A controlled trial of colchicine to reduce the elastase load in the lungs of cigarette smokers with chronic obstructive pulmonary disease.

Current data suggest that emphysema in smokers is caused at least in part by the unrestrained action of neutrophil elastase on pulmonary tissues. Since colchicine reduces the secretion of enzymes from stimulated neutrophils, we designed a clinical trial to determine if colchicine could reduce the elastase load in the lungs or several putative indicators of elastin destruction. We carried out a prospective, double-blind, randomized, and placebo-controlled clinical trial. Outpatients seeking treatment for chronic obstructive pulmonary disease at the University of Texas Health Center at Tyler who met specific criteria were recruited into the study. A group of 46 cigarette smokers between 45 and 75 yr of age with chronic obstructive pulmonary disease (COPD) were studied. Colchicine or placebo was given orally in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of Theodur orally and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization. The patients were then randomized and treated for 14 days with colchicine, and the measurements were repeated. Modifications in plasma elastin peptides and neutrophil elastase-generated fibrinopeptide A, urinary desmosines, and bronchoalveolar lavage fluid neutrophils or neutrophil elastase were the indicators of success or failure of the treatment. Pre- and posttreatment measurements in each patient and the difference between colchicine-treated and placebo-treated groups were compared. There were no statistically significant differences in either of the two types of analyses in any of the variables. We conclude that variables related to elastase load in the lungs were not modified by colchicine treatment. If a drug can be identified that is successful in modifying one of these variables, it would then have to be tested in a large-scale clinical trial in which the rate of decline in the FEV1.0 or mortality would be measured. The data presented here may provide useful information about the variability of key measurements of elastase load in the lungs and the breakdown of elastin and may aid investigators in designing similar trials in the future.

Aged↗