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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 343 records · Page 19Linked to original sources

Maternal respiratory function following normal vaginal delivery.

Forced expiratory volume (FEV(1)) forced vital capacity (FVC), peak expiratory flow (PEF) and maximum expiratory pressure (P(E)max) were measured in 11 healthy women 2, 4, 8, 24, 48 and 72 hours after normal vaginal delivery and repeated after 6-8 weeks. There was a significant (P<0.05) reduction in the P(E)max up to 4 hours after delivery. In contrast, there was no significant reduction in FEV(1) or FVC at any of the time periods, and PEF showed a significant reduction only at 2 hours after delivery. This indicates that P(E)max is a more sensitive measure of respiratory muscle strength and that this is reduced for at least 4 hours after delivery. Any anaesthetic given during this period should take into consideration that the ability to cough effectively may be impaired.

Journal Article↗

First-trimester simple hygroma: cause and outcome.

OBJECTIVE: First-trimester fetuses with simple nuchal hygromas represent a population that is different from midgestation nuchal cystic hygroma in terms of karyotype abnormalities and long-term prognosis. STUDY DESIGN: Sixty-eight consecutive fetuses diagnosed with simple nuchal hygromas between 10 and 14 weeks' gestation were evaluated ultrasonographically and karyotyped. Those with normal chromosome complements were ultrasonographically monitored throughout the remainder of the pregnancy for resolution of their hygromas. RESULTS: Twenty-three of 27 fetuses with normal karyotypes resolved their hygromas within 4 weeks of diagnosis and were phenotypically normal at birth. Forty-one fetuses were karyotypically abnormal, with trisomy 21 being the most common abnormality. CONCLUSIONS: Fetuses with first-trimester simple nuchal hygromas are at high risk for aneuploidy and should be offered prenatal testing. Such fetuses with normal karyotypes will likely resolve their hygromas by 18 weeks' gestation, and most will be phenotypically normal at birth.

Chromosomes, Human, Pair 21↗

The effect of dietary calcium intake in weanling rats on the efficiency of calcium absorption.

Rats were weaned onto high (HCa, 14.6 g/kg)- or low (LCa, 3.88 g/kg)-Ca diets for 12 d and the efficiency of absorption of Ca measured from 20 mg Ca (as CaCl2, labelled with 47Ca) by means of whole-body counting. The LCa group absorbed 74% of the test dose and the HCa group 60% of the test dose (P < 0.001). All animals were then given the LCa diet for 6 weeks and the absorption test repeated. This time there was no difference in efficiency of absorption (HCa 54%, LCa 57%). The femur dry weight was significantly lower in the group initially fed on the LCa diet, but the Ca concentration was similar to that of the HCa group. The results do not lend support to the suggestion that early dietary exposure to Ca manifests itself as a difference in Ca metabolism in later life. They do, however, highlight the importance of adequate Ca intake during critical periods of growth.

Animals↗

A parallel evaluation of four automated hematology analyzers.

A parallel evaluation was performed on four automated hematology analyzers: the Celldyn 3000 (Unipath Corp., Mountain View, CA), the Coulter STKS (Coulter Electronics Inc., Hialeah, FL), the Sysmex NE-8000 (Baxter Healthcare Corp., McGaw Park, IL), and the Technicon H*2 (Miles Corp., Tarrytown, NY). The protocol included evaluation of the complete blood count and differential leukocyte count (DLC) parameters. The DLC evaluation was performed using the National Committee for Clinical Laboratory Studies H20-A protocol. Based on this evaluation, the authors could not identify a single instrument that was clearly superior to the others. Overall, the four instruments were found to be safe and effective for diagnostic use; however, there were areas in which their performance was less than optimal. Particular questions were raised regarding the clinical usefulness of instrumental "flags" to identify qualitative leukocyte abnormalities. The results are discussed in relation to the selection of instruments for specific clinical applications.

Blood Cell Count↗

Comparison of portable emergency ventilators using a lung model.

A lung model was used to test the performance of five emergency ventilators (MEDUMAT Elektronik, MEDUMAT Variabel, OSIRIS, OXYLOG and rescuPAC 2DM). The model comprised two glass jars filled with water to suitable compliances and connecting tubes. A resistance (obstruction) was added to one of the "bronchial" tubes in order to simulate a patient with obstructive lung disease. Preset minute volume was compared with measured minute volume and the gas distribution produced by the different ventilators. Acceptable performance was found with the MEDUMAT Elektronik, MEDUMAT Variabel, OSIRIS and OXYLOG ventilators.

Critical Care↗

The involvement of general practitioners in the care of patients with human immunodeficiency virus infection: current practice and future implications.

The objective was to determine the current use of their general practitioner (GP) by patients with human immunodeficiency virus (HIV) infection and whether such patients would be interested in having 'shared care' between a specialist HIV clinic and their GP. A questionnaire was administered to 203 HIV-positive men attending the HIV outpatient clinic of a central London teaching hospital. The main outcome measures were patient characteristics, numbers of patients registered with a GP, numbers of patients with a GP aware of their diagnosis, contacts with the GP in the last year and level of interest and shared care. Eighty-five per cent of patients were registered with a GP of whom 67% knew of the diagnosis. Those diagnosed for more than 2 years were significantly more likely to have an informed GP. A total of 73% of those registered had visited their GP in the previous year although only 27% had visited for an HIV-related problem. Only 19% had a GP actively involved in their HIV care. In all 51% of the patients indicated an interest in having shared care between the clinic and their GP. A high proportion of HIV patients are registered with and attend a GP although they rarely consult for HIV-related problems. A significant proportion of patients expressed interest in having shared care suggesting that there is the potential for increased GP involvement in the care of patients with HIV infection.

Adolescent↗

Blood lymphocyte clonal excess in advanced non-Hodgkin's lymphoma. Relation to clinical data and prognosis.

BACKGROUND: Increasingly sensitive methods, based on the monoclonal nature of NHL, are used to detect tumour spread and remaining disease. Since the lymphomas are thought to arise due to successive genetic changes, clonal cells in different compartments do not necessarily represent the same disease despite a common clonal origin. PATIENTS AND METHODS: In 179 patients with advanced NHL, clonal cells in peripheral blood were identified by light chain restriction analysed in flow cytometry, i.e. clonal excess (CE) analysis. RESULTS: CE was more common in low grade NHL (52%) than in high grade NHL (21%). In patients with a normal lymphocyte count CE was found in 23%. CE was significantly correlated to small cell histology and bone marrow involvement. In high grade NHL CE in peripheral blood was more common in those with discordant small or mixed cell involvement of the bone marrow. CE was significantly related to failure to achieve remission in both histologic subgroups. Survival was not influenced by CE in low grade NHL but in high grade NHL. In multivariate analyses however, CE did not emerge as an independent risk factor but age, B-symptoms and LDH were the major factors. CONCLUSIONS: The utility of blood CE analyses in clinical praxis has still to be settled and the prognostic value of CE per se seem limited in the current perspective. The existence of CE in high grade NHL might be a clue of different biology as compared to de novo high grade NHL.

Adult↗

Hyperinsulinaemia is associated with stimulation of cholesterol synthesis in both type 1 and type 2 diabetes.

The effect of hyperinsulinaemia and hyperglycaemia on cholesterol synthesis was examined in lymphocytes from diabetic subjects. The first part of the study involved the provocation of hyperinsulinaemia by consumption of a carbohydrate-rich meal, in obese patients with Type 2 diabetes mellitus. Cholesterol synthesis was measured before and 4 h after completing the meal. Results were compared to groups of obese non-diabetic patients and to control subjects. Analysis of the three groups demonstrated that the percentage change in cholesterol synthesis was directly proportional to the percentage rise in serum insulin (r = 0.49, p < 0.05). This physiological study demonstrated that postprandial hyperinsulinaemia promoted cholesterol synthesis; however, we could not estimate the effect of the meal on cholesterologenesis. To study hyperinsulinaemia in isolation, we examined the effects of varying insulin infusion rates for 4 h at either low or high levels of serum glucose using the glucose clamp technique in young Type 1 diabetic patients. Cholesterol synthesis in lymphocytes was again measured before and after the study period. Hyperinsulinaemia stimulated cholesterol synthesis (+28.6%, p < 0.05) but hyperglycaemia alone did not exhibit this effect (-1.7% NS). The combination of hyperinsulinaemia and hyperglycaemia produced the greatest increase in cholesterol synthesis (+51.4%, p < 0.05) but this increase was not significantly different from hyperinsulinaemia alone. The percentage increase in serum insulin levels was again proportional to the percentage change in cholesterol synthesis (r = 0.46, p < 0.05).

Acetates↗

The regulation of post-prandial cellular cholesterol metabolism in type 2 diabetic and non-diabetic subjects.

The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolaemia and non-diabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 +/- 0.95 (SEM) was significantly higher than that for the control group of 26.2 +/- 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 +/- 0.22, 2.27 +/- 0.34, and 1.58 +/- 0.18 mmol l-1, respectively) compared with normocholesterolaemic non-diabetic subjects (0.75 +/- 0.12 mmol l-1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 +/- 0.08 and 1.04 +/- 0.06 mmol l-1) compared to the corresponding non-diabetic groups (1.29 +/- 0.11 and 1.45 +/- 0.17 mmol l-1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Tumor necrosis factor-alpha activates pulmonary artery endothelial protein kinase C.

We investigated the hypothesis that tumor necrosis factor-alpha (TNF) activates pulmonary endothelial protein kinase C (PKC). Confluent bovine pulmonary artery endothelial monolayers were exposed to recombinant human TNF, and the translocation of PKC, an indicator of enzyme activation, was studied using both slot immunoblotting and immunofluorescence. For slot immunoblot analysis, membrane and cytosol lysate fractions were prepared, and PKC antigen was assessed using MC5 monoclonal anti-PKC antibody. TNF (1,000 U/ml for 15 min) induced translocation of PKC into the membrane. Immunofluorescence analysis with the MC5 antibody was also used. Monolayers treated with culture medium showed diffuse cytoplasmic fluorescence. In contrast, treatment with either TNF (1,000 U/ml for 15 min) or 1,2-dioctanoylglycerol (4 x 10(-5) M for 5 min), a diacylglycerol that activates PKC, resulted in translocation of fluorescence to the cell periphery; fine, punctate PKC-associated fluorescence was localized to the margins of cells. The TNF-induced translocation of PKC was inhibited using either IP-300 polyclonal anti-TNF antibody (indicating that the TNF effect was not due to the vehicle or contaminating endotoxin) or calphostin C (10(-6) M for 15 min), which inhibits PKC activation by interacting with the regulatory diacylglycerol-binding domain. TNF treatment had no effect on either the content of PKC, or of total protein, in the membrane + cytosol, and cycloheximide (40 microM for 5 min) did not alter the translocation of PKC induced by TNF; these results indicate that the effect of TNF on PKC translocation was related to neither de novo membrane synthesis of PKC (as opposed to translocation per se) nor nonspecific augmentation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tumor necrosis factor-alpha alters pulmonary vasoreactivity via neutrophil-derived oxidants.

We postulated that tumor necrosis factor-alpha (TNF) "primes" the lung for the development of pulmonary vasoconstriction and edema by inducing the release of polymorphonuclear leukocyte (PMN)-derived reactive oxidant species (ROS). Guinea pigs were injected with TNF (1.6 x 10(5) U/kg ip), and the lungs isolated 18 h later. Compared with controls, TNF pretreatment resulted in 1) greater increases in lung weight and capillary pressure in response to the thromboxane A2 mimetic U-46619 (365 pmol/min) and 2) an increase in the dose of acetylcholine (ACh) causing 50% of maximal dilation (EC50). The vascular effects of TNF were associated with 1) decreased lung effluent nitrite (NO2-, oxidation product of nitric oxide), 2) increased lung effluent superoxide (O2-), and 3) increased lung myeloperoxidase (MPO). Superoxide dismutase (SOD, 10 U/ml) prevented 1) the effects of TNF on the hemodynamic responses to U-46619 and ACh and 2) the TNF-induced decrease in NO2-. The effects of TNF on lung MPO and effluent O2- were prevented using cyclophosphamide intraperitoneally (100 mg/kg 5 days before, and 50 mg/kg 1 day before, treatment with TNF or control). The data suggest that ROS generated from PMN mediate the decrease in nitric oxide and altered pulmonary vasoreactivity induced by TNF.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Skeletal muscle blood flow. A possible link between insulin resistance and blood pressure.

Insulin resistance has recently been found to be a common feature of essential hypertension. We have tested the hypothesis that reduced skeletal muscle blood flow in response to insulin may at least partially account for the wide range of insulin sensitivity observed in normotensive subjects. To this end, we studied 19 lean (body mass index < or = 27) subjects exhibiting basal mean arterial pressures ranging from 58 to 110 mm Hg. All subjects were normotensive with the exception of one. Each subject was studied at baseline and during a hyperinsulinemic (600 milliunits/m2 per minute) euglycemic clamp to quantitate insulin sensitivity. Mean arterial pressure was monitored invasively, and both leg (muscle) blood flow and cardiac output were measured by indicator dilution techniques, allowing the determination of both systemic and leg (or muscle) vascular resistance. In response to hyperinsulinemia, both cardiac output and leg blood flow increased approximately 37% and 80% (p < 0.01), respectively. Rates of insulin-mediated glucose uptake were inversely correlated with the baseline mean arterial pressure (r = -0.62, p < 0.01). The individual increment in leg blood flow above baseline in response to insulin was inversely proportional to the height of the baseline mean arterial pressure (r = -0.59, p < 0.01). Mean arterial pressure and insulin-mediated glucose uptake were not correlated with either age or body fat content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytokines increase neutral endopeptidase activity in lung fibroblasts.

Fibroblasts of the pulmonary interstitium are intimately involved in the response of the lung to inflammation as well as in repair of injured tissues. The response of fibroblasts within an inflammatory site appears to be directed, in part, by peptide mediators. Neutral endopeptidase (NEP), a metallopeptidase on the surface membrane of fibroblasts, can inactivate various vasoactive peptides, including kinins and tachykinins. Because lung fibroblasts both secrete cytokines and respond to mediators within the immediate environment, NEP might be regulated by locally generated cytokines. We found that several cytokines, including interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor, interleukin-6, and granulocyte macrophage colony-stimulating factor, enhanced activity of NEP on the surface of intact fibroblasts. In contrast, cultured pleural mesothelial cells had much lower levels of NEP than fibroblasts, and the enzyme was not enhanced by either IL-1 or TNF-alpha. Further studies with IL-1 showed that the effect required at least 6 h of exposure to the cytokine and depended upon final cytokine concentration. Combinations of IL-1 with other cytokines increased NEP activity beyond that in cells treated with individual cytokines, but combinations had less than additive effects. Selected pharmacologic agents indicated that the mechanism involves second messenger pathways. The cytokine effect on NEP was attenuated by indomethacin, an inhibitor of cyclooxygenase, by N-[2-(methylamino) ethyl]-5-isoquinolinesulfonamide dihydrochloride, an inhibitor of protein kinase, and by adenosine 3',5' cyclic monophosphothionate, an analog of cyclic adenosine monophosphate (cAMP) that competitively inhibits the cAMP signal pathway. It was mimicked by dibutyryl cAMP and by forskolin, an activator of adenyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Bucladesine↗

Genetic amniocentesis and chorionic villus sampling.

With the expanding list of prenatally detectable disorders, increasing numbers of patients are presented with the option of invasive prenatal diagnosis. Care providers need to address questions regarding the safety and accuracy of these procedures, as well as the indication. This article reviews these issues for genetic amniocentesis and chorionic villus sampling.

Amniocentesis↗

Gene activation in response to neural induction.

In order to study the molecular processes involved in the final steps of neural induction, we are investigating the transcriptional regulation of the Xenopus laevis neural cell adhesion molecule (NCAM) gene. NCAM is expressed very early during neural development and its expression is dependent on neural induction signals. Using microinjection of reporter gene constructions into fertilized frog eggs, we have shown that cloned copies of the NCAM promoter respond appropriately to neural induction signals. Examination of the Xenopus NCAM promoter reveals a number of potential regulatory elements. We have directed our attention to a small region of the promoter that is highly conserved over large evolutionary distances. This region contains an enhancer, the OZ element, and also a silencer element, the N-box. We have purified DNA DNA proteins that interact specifically with both the OZ enhancer and the N-box silencer sequences. A model suggesting a role for these regulatory factors during neural induction is presented.

Animals↗

Introducing the Objective Structured Clinical Examination to a family practice residency program.

BACKGROUND: The Objective Structured Clinical Examination (OSCE) is a multiple station examination where examinees are expected to demonstrate mastery of a competency within a specified time at each station. It is commonly used to evaluate medical students and is less often used in residency programs. This paper describes the process of introducing a 12-station OSCE to a university-based family practice residency program. METHODS: The examination evaluated cognitive, psychomotor, and behavioral competencies in 31 residents. The 10-minute stations included: two simulated patients; two skills demonstrations; six modified essay questions, four in response to a written scenario and two in response to a video trigger; and two rest stations. Feedback was given in a large group at the conclusion of the examination. RESULTS: Construct validity was demonstrated by increasing scores with training year; concurrent validity was demonstrated by significant correlations of the OSCE scores with the American Board of Family Practice in-training examination scores and the residents' monthly rotation evaluation scores. Reliability was demonstrated by significant correlation between the scores of the OSCE and its subsets. CONCLUSIONS: As a method of formative evaluation, the OSCE had an overall positive response from residents and faculty.

Clinical Competence↗

Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling.

OBJECTIVE: To evaluate prospectively the relative risks and accuracy of first-trimester chorionic villus sampling (CVS) and second-trimester amniocentesis in the genetic evaluation of twin gestations. METHODS: Between March 1984 and August 1990, patients presenting for prenatal diagnosis of a twin gestation of less than 12 weeks were offered sampling by either first-trimester CVS or amniocentesis at 16-18 weeks' gestation. Selection was based solely on patient preference and was obtained before ultrasound identification of placental position. Women presenting beyond 12 weeks' gestation were sampled by amniocentesis. Clinical and laboratory outcomes were evaluated. RESULTS: Eighty-one women had amniocentesis (nine of whom also had CVS), and 161 women had CVS. All fetuses in both groups were successfully sampled and karyotyped; 85.3% of the amniocentesis patients and 75.8% of the CVS patients were sampled in two or fewer passes (P = not significant). There were three cases of twin-twin villus contamination following CVS; one of these led to incorrect gender assignment because of erroneous laboratory interpretation. Loss of the entire pregnancy from the time of sampling until the 28th week of gestation followed amniocentesis in 2.9% of the cass and CVS in 3.2%. The total fetal loss rates were 9.3% for amniocentesis and 4.9% for CVS (P = not significant). When pregnancies having mosaic or abnormal karyotype results are excluded, the total amniocentesis loss rate remained 9.3% and the CVS loss rate became 3.9% (P < .05). CONCLUSION: In the hands of experienced operators, CVS is at least as safe and effective as amniocentesis for the prenatal diagnosis of twin gestations.

Abortion, Eugenic↗