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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 307 records · Page 17Linked to original sources
PubMed1994

Biochemical and molecular genetic studies of abdominal aortic aneurysm in an Irish population.

Abdominal aortic aneurysm (AAA) is a common disease of the elderly exhibiting a complex aetiology. In a survey of 82 Irish aneurysm patients, compared to 79 age- and sex-matched control subjects, we have investigated a number of potential biochemical and molecular genetic markers which are amenable to analysis from blood specimens and which might have predictive value for AAA. No significant differences were observed between patients and control subjects in relation to serum lipids, leucocyte elastase activity or serum alpha 1-antitrypsin concentration. We have used the polymerase chain reaction to screen the patient and control groups in search of disease-associated genetic variation on chromosome 16, particularly in the region of the Cholesteryl Ester Transfer Protein (CETP) gene. Although variation in allele frequencies was detected between patients and controls at the four marker loci studied, no significant gene-disease associations were detected. The absence of gene-disease associations in our study may indicate that the genetic component in the aetiology of AAA in Ireland differs from that in the UK. Alternatively, it may indicate that the high degree of polymorphism at microsatellite loci may make them unsuitable as markers for the study of gene-disease associations in moderately sized populations. We therefore conclude that the biochemical and molecular genetic markers which we have examined are of no predictive value, and that ultrasonography remains the screening modality of choice for abdominal aortic aneurysm.

Aged↗
PubMed1994

Serum melatonin levels in melanoma patients after repeated oral administration.

The goal of this study was to determine the effect of oral melatonin in divided doses on plasma melatonin levels in patients with metastatic melanoma. Hourly blood samples were obtained from five patients for 24 h prior to melatonin administration and for 24 h during oral administration of melatonin, 50 mg every 4 h. In two of the five patients, the expected nocturnal plasma melatonin peak was observed. Oral melatonin was well absorbed. Plasma melatonin levels exhibited six peaks and troughs, were two to four-fold higher during peaks than troughs, and remained more than 25 times higher than peak pretreatment melatonin levels, even during troughs. Divided oral doses of melatonin were well tolerated and maintained plasma melatonin levels 25-80 times higher than endogenous peak values.

Administration, Oral↗
PubMed1994

Splenic rupture in hemophilia.

PURPOSE: Little information is available regarding splenic injury in patients with hemophilia. We describe here the management of splenic rupture in five of our patients with hemophilia and summarize the literature describing this complication. PATIENTS AND METHODS: Two human immunodeficiency virus-seropositive patients were managed medically and did not require splenectomy. A third patient had a high titer inhibitor to both porcine and human factor VIII and required emergency splenectomy. Two boys had not been previously diagnosed with hemophilia until they underwent splenectomy after abdominal trauma. RESULTS: All five patients survived. CONCLUSIONS: These cases demonstrate that nonsurgical management of splenic injury in patients with hemophilia can be performed safely and that splenectomy can be successfully performed despite a high titer of factor VIII inhibitor.

Adolescent↗
PubMed1994

Bacteriophage-like particle of Rochalimaea henselae.

An extracellular particle approximately 40 nM in diameter was detected in culture supernatant from the fastidious bacterium Rochalimaea henselae. This particle has at least three associated proteins and contains 14 kbp linear DNA segments that are heterogeneous in sequence. The 14 kbp DNA was also present in R. henselae cells as an extrachromosomal element for all 14 strains tested. Despite attempts to induce lysis of R. henselae, plaque formation was not observed. A similar particle, also containing 14 kbp DNA, was observed in Bartonella bacilliformis, and may be analogous to a bacteriophage that has been described elsewhere for B. bacilliformis.

Bacteriophages↗
PubMed1994

Clustering of perinatal markers of birth asphyxia and outcome at age five years.

OBJECTIVES: In a cohort of term infants with cerebral depression at delivery, to investigate the association of perinatal signs of birth asphyxia, particularly abnormal fetal heart rate patterns in labour, acidaemia, and serious neonatal encephalopathy, with neurodevelopmental outcome at age five years. DESIGN: Five year follow up study of a birth cohort. SETTING: Regional maternity hospital. SUBJECTS: One hundred and eighty-four singleton infants with a 1 min Apgar score < or = 3, born at term between January 1984 and September 1985. MAIN OUTCOME MEASURES: Neonatal death, cerebral palsy, and scores on a battery of neurodevelopmental tests at age five. RESULTS: Seven infants had a cluster of perinatal signs suggestive of birth asphyxia; all included serious neonatal encephalopathy. Three of these infants died neonatally, three had spastic quadriparesis with profound developmental delay, and one was unimpaired at the age of five. Among the remaining infants, no association was found between severely abnormal fetal heart rate patterns in labour and scores on neurodevelopmental tests, or between acid-base status at delivery and test scores. CONCLUSIONS: Birth asphyxia, identified by a cluster of abnormal perinatal signs, including serious neonatal encephalopathy, has a poor prognosis. If serious encephalopathy is not present, cerebral depression at birth preceded by abnormal fetal heart rate patterns in labour, or with acid-base derangement, is not predictive of later impairment.

Acid-Base Imbalance↗
PubMed1994

First trimester maternal serum pregnancy-associated plasma protein A and pregnancy-specific beta 1-glycoprotein in fetal trisomies.

OBJECTIVE: To examine the potential value of maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta 1-glycoprotein (SP1) in the detection of fetal trisomy. DESIGN: Cross-sectional study. SETTING: The Harris Birthright Research Centre For Fetal Medicine, King's College Hospital Medical School, London, UK and Division of Maternal-Fetal Medicine, Jefferson Medical College, Philadelphia, USA. SUBJECTS AND METHODS: Maternal serum PAPP-A and SP1 concentrations were measured at 10 to 13 weeks gestation in samples from 42 pregnancies with fetal trisomy (trisomy 21, n = 29; trisomy 18, n = 9; trisomy 13, n = 4) and in samples from 210 matched controls. RESULTS: In controls, both maternal serum PAPP-A and SP1 increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SP1 did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in cases with fetal trisomy 21, the deviation was more pronounced at 10 to 11 weeks than at 12 to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancies with trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. CONCLUSION: Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies.

Adult↗
PubMed1994

Development of the Diploma in Clinical Dentistry (Conscious Sedation and Pain Control) Faculty of Dentistry, University of Sydney.

The Diploma in Clinical Dentistry (Conscious Sedation and Pain Control) of the Faculty of Dentistry, University of Sydney, is the first dedicated programme devoted to this field in Australia. Its development followed a decision by the Dental Board of New South Wales to require a formal qualification from the University of Sydney before dental practitioners could offer sedation and pain management in practice. The programme is conducted at Westmead Hospital in conjunction with the Department of Anaesthetics, and satisfies the guidelines developed by the Royal Australasian College of Dental Surgeons and the Royal Australasian College of Surgeons. The course is conducted either over one or two years, with block sessions requiring attendance at Westmead Hospital, together with assignments which are completed outside the block sessions. In this way, a dental practitioner enrolled in the programme is able to continue practice. The block sessions need not be completed over one year, but must be completed within two years.

Anesthesia, Dental↗
PubMed1994

Chemical and glass thermometers for axillary temperatures: how do they compare?

Axillary temperatures recorded with a disposable chemical thermometer (DCT) measured a mean 0.29 degrees C higher than a mercury in glass thermometer (MGT) but differences could be wide. Differences between the same methods were however also wide. The DCT is safe and easy to use. Provided the higher readings are taken into consideration it is a suitable alternative to the MGT.

Adolescent↗
PubMed1994

Clinical associations of prenatal ischaemic white matter injury.

Neuropathological examinations were carried out at necropsy on 274 cases of intrauterine death or neonatal death at or before three days after birth. Fifty six (20.4%) subjects had evidence of prenatal ischaemic brain damage. On review of the maternal case notes to ascertain antenatal clinical associations there was an increased incidence of intrauterine growth retardation, either based on birth weight for gestational age (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.1 to 3.7) or diagnosed antenatally (OR 2.7; 95% CI 1.3 to 5.6). Oligohydramnios was also more common (OR 2.9; 95% CI 1.2 to 7.0). The association of intrauterine growth retardation and white matter damage remained after excluding fetuses with a major congenital anomaly (OR 2.4; 95% CI 1.1 to 5.1). The findings suggest that chronic intrauterine hypoxia may be associated with damage to cerebral white matter among fetuses and infants who die. The relation between ischaemic white matter damage and cerebral palsy among survivors remains speculative.

Brain↗
PubMed1994

Comparison of mortality and rates of cerebral palsy in two populations of very low birthweight infants.

Comparisons of mortality and rates of cerebral palsy in different populations can be confusing. This is illustrated by comparing two populations of very low birthweight infants born in the 1980s, one from the Netherlands, the other from the UK (Oxford region). Although a number of biases were controlled for while comparing two large geographically defined populations, by assessing the survivors at similar ages and describing their health status in a standard way, some problems in interpretation of outcome remained. Differences in registration practice of live births at early gestational ages, as well as differences in withholding or withdrawing treatment, which occurred in about half of the cases of neonatal death in the Netherlands and in about one third of those in the Oxford region, may have influenced the incidence of registered live births, neonatal mortality, and the rate of cerebral palsy.

Blindness↗
PubMed1994

Cerebral palsy and neonatal encephalopathy.

A retrospective cohort study was carried out to test the hypothesis that children born at term with cerebral palsy with signs of neurological dysfunction preceded by depression at birth (termed neonatal encephalopathy) differ from those without such signs in the frequency of antenatal and perinatal factors, and in the severity and characteristics of their impairment and disability. The study was carried out in the area covered by Oxford Regional Health Authority. Antenatal, intrapartum, neonatal factors, and the later clinical status of the two groups of children were used as the main outcome measures. Although most maternal and antenatal characteristics were similar in the two groups, the mothers of children with a history of neonatal encephalopathy were more likely to be primigravidae (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.0 to 4.3) and to have a pregnancy of greater than 41 weeks' gestation (OR 3.5; 95% CI 1.0 to 12.1). Intrapartum complications were more frequent in the neonatal encephalopathy group: meconium staining of the amniotic fluid (OR 3.5; 95% CI 1.5 to 7.8), an ominous first stage cardiotocograph (OR 10.2; 95% CI 2.9 to 36.4), with a longer median duration of abnormality (200 v 48 minutes). At 5 years of age those with neonatal encephalopathy were more likely to have developed spastic quadriplegia (OR 4.8; 95% CI 2.2 to 10.5), to have visual impairment (OR 3.0; 95% CI 1.0 to 8.6), and to be non-walking (OR 4.0; 95% CI 1.8 to 8.8) than those without neonatal encephalopathy. Children with cerebral palsy who were born at term and have neonatal encephalopathy are more likely to have had signs of intrapartum asphyxia and are more likely to have a more severe form of cerebral palsy than those without a history of neonatal encephalopathy. Although this group represents only one in 10 of all cases of cerebral palsy, some of these may be obstetrically preventable.

Apgar Score↗
PubMed1994

Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.

A case of dilated cardiomyopathy in a young boy secondary to type II 3-methylglutaconic aciduria is described. A metabolic cause for his dilated cardiomyopathy was suspected because of the development on the electrocardiogram of an unusual "camel's hump" shape of the T waves, and of progressive thickening with increasing echogenicity of the left ventricular wall. He initially improved on digoxin treatment, but did not maintain the response with conventional dietary treatment for this condition. Supplementation with L-carnitine was associated with rapid deterioration in cardiac state, and may be contraindicated in this condition. At a point when the patient was moribund, large doses of pantothenic acid, a precursor of coenzyme A, produced a dramatic and sustained improvement in myocardial function and in growth, neutrophil cell count, hypocholesterolaemia, and hyperuricaemia, which suggests that limitation of availability of coenzyme A is a fundamental pathological process in this condition. The clinical improvement has been maintained for 13 months, and myocardial function is now nearly normal. Oral pantothenol, unlike pantothenic acid, is not efficacious.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Skeletal muscle blood flow independently modulates insulin-mediated glucose uptake.

Insulin-mediated glucose uptake (IMGU) occurs principally in skeletal muscle. To directly examine whether skeletal muscle perfusion (F) can directly and independently modulate IMGU, we combined the hyperinsulinemic euglycemic clamp and leg balance techniques [leg glucose uptake (LGU) = arteriovenous glucose difference (delta AVG) x F]. Young (< 40 yr) healthy lean subjects were studied during euglycemic hyperinsulinemia of approximately 23 microU/ml (group I, n = 8) and approximately 950 microU/ml (group II, n = 6). Femoral delta AVG and leg F were measured, and LGU was calculated at baseline after approximately 200 min of steady-state hyperinsulinemia alone and during a superimposed intrafemoral artery infusion of methacholine hydrochloride designed to increase leg F two- to threefold. In groups I and II, insulin raised the delta AVG approximately 4- and 14-fold, respectively (P < 0.0001). Leg F was unchanged during the low-dose insulin infusion (group I) but increased 112 +/- 35% in group II (P < 0.001). During methacholine infusion the delta AVG narrowed 35.9 +/- 6.8% (P < 0.01) and 20.5 +/- 4.8% (P < 0.05) in groups I and II, respectively. Leg F rose 224 +/- 30% (P < 0.01) and 79 +/- 13% (P < 0.05) above the flow rate achieved with insulin alone. Thus, during methacholine flow modulation, LGU increased 116 +/- 36% (P < 0.01) and 47 +/- 11% (P < 0.05) in groups I and II, respectively. In conclusion, skeletal muscle perfusion during hyperinsulinemia can act as an independent determinant of IMGU.

Adult↗
PubMed1994

Activation of protein kinase C mediates altered pulmonary vasoreactivity induced by tumor necrosis factor-alpha.

We postulated that tumor necrosis factor-alpha (TNF) "primes" the lung for the development of pulmonary vasoconstriction and edema by activating protein kinase C (PKC). Guinea pigs were injected with TNF (1.6 x 10(5) U/kg i.p.), and the lungs were isolated 4 h later. Compared with controls, TNF pretreatment resulted in greater increases in pulmonary vascular resistance and pressure and lung weight, in response to the thromboxane A2 mimetic, U-46619 (122 pmol/min). Treatment with TNF resulted in 1) pulmonary arterial endothelial PKC activation, 2) increased lung polymorphonuclear neutrophil (PMN) sequestration, 3) increased levels of superoxide radical (O2.) in lung effluent, and 4) decreased nitrite levels (NO2-, oxidation product of nitric oxide) in lung effluent. Intraperitoneal treatment with calphostin C (3 microM, 15 min prior to treatment with TNF) prevented the effects of TNF on 1) PKC activation, 2) the hemodynamic responses to U-46619, and 3) the levels of NO2- and O2(.). PKC activation does not mediate TNF-induced lung sequestration of PMN, since calphostin C had no effect on lung myeloperoxidase activity. The data suggest that PKC activation mediates TNF-induced 1) increases in O2., 2) decreases in NO2-, and 3) increases in vasoreactivity and edema in response to U-46619.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Tumor necrosis factor-alpha decreases pulmonary artery endothelial nitrovasodilator via protein kinase C.

We postulated that tumor necrosis factor-alpha (TNF) decreases endothelium-derived nitrovasodilator(s) via a protein kinase C (PKC)-dependent pathway. Calf pulmonary artery endothelial monolayers (PAEM) were treated with TNF (10, 100, and 1,000 U/ml) for 15 min or 18 h during an 18-h incubation. At the end of the incubation, the cell lysate and supernatant were harvested. Compared with controls, an 18-h incubation with TNF (100 and 1,000 U/ml) resulted in a decrease in NO2- [the oxidation product of nitric oxide (NO)] in PAEM lysate and supernatant. TNF (100 U/ml) treatment for 15 min did not suppress NO2- levels. The decrease in NO2- and the increase in lipid peroxides in response to TNF were prevented by pretreatment (15 min prior to and throughout the incubation) with either calphostin C (1 microM; a specific PKC inhibitor) or the antioxidants N-acetylcysteine (1 mM), 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron) (10 mM), and superoxide dismutase (10 U/ml). Treatment with phorbol 12-myristate 13-acetate (PMA, 1 microM for 15 min), an activator of PKC, decreased NO2- similarly to TNF. Pretreatment with calphostin C or N-acetylcysteine prior to TNF (10 U/ml) revealed an increase in NO2- levels above control treatment. Treatment with the NO synthase antagonists NG-monomethyl-L-arginine (1 mM) and N-nitroso-L-arginine (1 mM) induced an L-arginine (1 mM)-dependent decrease in NO2- in control but not in TNF-treated PAEM. The induction of NO2- by calcium ionophore (A23187; 500 nM) was not affected by treatment with TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗