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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1998

Screening of maternal serum for fetal Down's syndrome in the first trimester.

BACKGROUND: Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester. METHODS: We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome. RESULTS: A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations. CONCLUSIONS: Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.

Adolescent↗
PubMed1998

Cellular cholesterol synthesis--the relationship to post-prandial glucose and insulin following weight loss.

Hyperinsulinaemia is a risk factor for atherosclerosis. We have previously demonstrated a relationship between hyperinsulinaemia and cellular cholesterol synthesis. In this paper we examine the separate relationship of glucose and insulin to cholesterol synthesis in three groups of obese patients. The first group was a group of non-insulin-dependent diabetic patients with a low post-prandial insulin response (n=8). The second group had non-insulin-dependent diabetes and a high insulin response (n=9). The third group were non-diabetic patients with a high post-prandial insulin (n=12). Six diabetic and seven non-diabetic patients who were hyperinsulinaemic on initial analysis, were re-examined following an 8% body weight reduction. Insulin resistance was defined as the ratio of area under curve for insulin/area under curve for glucose. Cellular cholesterol synthesis was measured in freshly isolated mononuclear leucocytes. Fasting cholesterol synthesis was similar in the three groups. In both diabetic and non-diabetic high insulin subjects cholesterol synthesis rose significantly after the meal (p < 0.05). Both hyperinsulinaemic groups showed a significantly greater change from baseline than did the non-hyperinsulinaemic group. There was a positive correlation between post-prandial cellular cholesterol synthesis and insulin resistance (p < 0.05). Following weight reduction patients were divided into two groups, those who did reduce insulin resistance (group 1) and those who did not reduce insulin resistance (group 2). The significant post-prandial increase in cholesterol synthesis was no longer seen in group 1 after weight loss whereas in group 2 after a similar weight loss the post-prandial cholesterol synthesis remained elevated. These results demonstrate that post-prandial hyperinsulinaemia is associated with increased cellular cholesterol synthesis. This increase in cholesterol synthesis is no longer seen in those patients in whom insulin resistance improved with weight reduction. This study suggests a mechanism for the association between insulin resistance and atherosclerosis.

Blood Glucose↗
PubMed1998

Pseudomonas aeruginosa necrotizing fasciitis: a case report.

A renal transplant recipient with necrotizing fasciitis due to Pseudomonas aeruginosa is presented. Only three other cases of necrotizing fasciitis due to this organism have been found in the literature. This is the first case of P. aeruginosa necrotizing fasciitis in a renal transplant patient to be reported. Prompt diagnosis, enabling treatment with appropriate antibiotics and early surgical intervention, was the key factor in his recovery.

Fasciitis, Necrotizing↗
PubMed1998

The effect of casting conditions on the biaxial flexural strength of glass-ceramic materials.

OBJECTIVE: To assess the effect of mould and glass casting temperatures on the biaxial flexural strength (BFS) of two different types of castable glass-ceramic, using existing laboratory equipment and techniques. METHODS: Two castable glass-ceramic materials were evaluated. One glass (LG3) is based on SiO2-Al2O3-P2O5-CaO-CaF2, and is similar in composition to glasses used in the manufacture of glass-ionomer cements. The other glass (SG3) is based on SiO2-K2O-Na2O-CaO-CaF2, and is a canasite-based material. Both materials were used to produce discs of 12 mm diameter and 2 mm thickness using the same lost-wax casting process as used for metal castings. Mould temperatures of between 500 degrees C and 1000 degrees C and glass casting temperatures of between 1100 degrees C and 1450 degrees C were evaluated. The cast discs were cerammed and the biaxial flexural strength determined with a Lloyd 2000 R tester. RESULTS: A significant difference was found for the BFS in the range of mould temperatures evaluated, with the optimum investment mould temperature being 590 degrees C for LG3 and 610 degrees C for SG3 (p = 0.0002 and p = 0.019, respectively). No significant differences were seen between any of the glass casting temperatures evaluated. SIGNIFICANCE: The mould temperature for castable glass-ceramic materials produced using the lost-wax casting process can have a significant effect on BFS. The optimum mould temperature may differ slightly depending on the type of material being used. The glass casting temperature of these materials does not appear to have a significant effect on BFS.

Analysis of Variance↗
PubMed1998

Mechanisms of bone loss after cardiac transplantation.

To determine the mechanism of bone loss after cardiac transplantation (CTX), we studied 50 men 0.5-47 months after CTX (ages 18-64 years) who received prednisolone and cyclosporin to prevent rejection, and 40 healthy men as controls (ages 20-70 years). We measured bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), bone resorption using urinary cross-linked N-terminal telopepides of type I collagen (NTx), and bone formation using osteocalcin (BGP) and bone alkaline phosphatase (BAP). The results from the controls were used to calculate z scores. BMD was significantly decreased at the lumbar spine, femoral neck, and total body, and bone turnover was significantly increased as assessed by NTx/creatinine, BGP, and BAP as compared with controls (p < 0.01 for all measurements). To evaluate the cause of the increased bone turnover we measured serum parathyroid hormone (PTH) by IRMA, and this was also elevated (p < 0.001). There was a significant correlation between serum PTH and BGP (r = 0.58, p < 0.01). To evaluate the cause of the increase in PTH, we measured serum calcium and it was decreased (p < 0.001), serum phosphorus was increased (p < 0.001), serum creatinine was increased (p < 0.001), and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D, RIA] was decreased (p = 0.03). Serum PTH correlated weakly with serum calcium (r = -0.41, p < 0.003) and with serum creatinine (r = 0.35, p = 0.01). There was a weak, but significant, correlation between serum creatinine and 1,25(OH)2D3 (r = 0.33, p = 0.03). Serum levels of testosterone and dehydroapiandrosterone sulfate were decreased after CTX but did not correlate with any other parameters. There was a weak negative correlation between prednisolone daily dose and serum BGP level (r = 0.29, p = 0.06) in those patients whose prednisolone current dose was >7.5 mg/day. We conclude that: (1) the low BMD found after CTX is associated with increased bone turnover which results, in turn, from renal impairment; (2) prednisolone is involved in rapid bone loss, whereas mild secondary hyperparathyroidism may be a major contributor to disorder of bone remodeling after this rapid loss; and (3) decreased androgen levels may not be a major factor resulting in bone loss in men after CTX.

Adolescent↗
PubMed1998

Linkage of Gordon's syndrome to the long arm of chromosome 17 in a region recently linked to familial essential hypertension.

Gordon's syndrome (GS) is a salt-sensitive, hyperkalaemic, familial hypertension syndrome which may masquerade in milder forms as essential hypertension. The response of hyperakalaemia to dietary salt restriction and to mineralocorticoids is heterogeneous, suggesting genetic heterogeneity. In a recently published study using small pedigrees, possible linkage of GS to chromosomes 1 and 17 was described. Studying the largest pedigree so far reported with GS, and using fluorescent-labelled microsatellite markers, we sought evidence of linkage to chromosomes 1 and 17. In this family there was no segregation of GS with any of the markers for chromosome 1. On chromosome 17, however, evidence of linkage was found with a maximum multipoint LOD score of 2.4 (the maximum LOD possible from the pedigree) over markers D17S250 and D17S934. This represents strong evidence in this pedigree for a responsible gene mutation on the long arm of chromosome 17. Recent reports of linkage for essential hypertension and, especially, familial essential hypertension within the same area of chromosome 17 containing the D17S934 marker raise the possibility that the same gene may be responsible for familial essential hypertension and for Gordon's syndrome.

Chromosomes, Human, Pair 1↗
PubMed1998

Pharmacokinetics and pharmacodynamics of the leukotriene B4 receptor antagonist CP-105,696 in man following single oral administration.

AIMS: CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)-4-hydroxy-chroman-7-yl] cyclopropane carboxylic acid is a potent, novel LTB4 receptor antagonist advanced to clinical trials to determine its efficacy in inflammatory diseases. The pharmacokinetics and pharmacodynamics of CP-105,696 were investigated in healthy male volunteers following oral administration of single doses of 5 to 640 mg. METHODS: Forty-eight subjects participated in a randomized, double-blind, parallel group study. Plasma and urine concentrations of CP-105,696 were determined at intervals after drug administration. As an indication of LTB4 receptor antagonism following oral administration of CP-105,696, the inhibiton of LTB4-induced upregulation of the neutrophil cell surface complement receptor (CR3), CD11b/CD18, was monitored at 4 h following drug administration using an ex vivo whole blood flow cytometry assay. RESULTS: Cmax and AUC(0, infinity) increased in a dose-related manner. Respective mean Cmax values were 0.54 to 30.41 microg ml(-1) following doses of 5 to 640 mg. Respective mean AUC(0, infinity) values were 1337 to 16819 microg ml(-1) h for the 40 to 640 mg dose groups. Plasma concentrations declined in a monoexponential manner, with terminal elimination half-lives ranging from 289 to 495 h. Group mean terminal elimination half-lives were dose-independent. Urinary excretion of unchanged drug accounted for < 1% of the administered dose. A linear relationship was observed between CP-105,696 plasma concentrations and inhibition of LTB4-mediated CD11b upregulation on human neutrophils in whole blood. CP-105,696 plasma concentrations of 5-6 microg ml(-1) were necessary to elicit a two-fold shift to the right of the LTB4 concentration response curve for CD11b upregulation. CONCLUSIONS: These studies demonstrate pharmacologically significant LTB4-receptor antagonism following a single dose of CP-105,696 and pharmacokinetics consistent with once-daily dosing.

Administration, Oral↗
PubMed1998

Painful subcutaneous fat necrosis of the newborn associated with intra-partum use of a calcium channel blocker.

Subcutaneous fat necrosis of the newborn (SCFN) is a relatively uncommon condition of the skin which is said to be benign and painless. We report an infant with extremely painful SCFN which was relieved only by opiate analgesia. SCFN normally resolves spontaneously within a few weeks. This case is, therefore, also unusual in that symptoms persisted beyond 6 months.

Amlodipine↗
PubMed1998

A comparison of two methods of follow-up in a trial of prophylactic volume expansion in preterm babies.

The outcome at age 2 years of preterm babies recruited into a three-arm randomised controlled trial of prophylactic volume expansion was ascertained in two ways: from a neurodevelopmental assessment performed by a paediatrician and from responses on a brief questionnaire completed by the child's personal health visitor. Of 776 babies recruited into the trial, 604 survived to the age of 2 years and the findings of a paediatric assessment were available for all survivors. Questionnaires were sent to the health visitors of 601 of the survivors; 513 (85.4%) were returned. There was sufficient information on the returned questionnaires to categorise 449 of the children as normal, impaired, moderately disabled or severely disabled. We were unable to detect a response bias by severity of disability. Agreement on individual questions ranged between 86.3% and 98.4%. There was some mismatch in the reporting of vision (weighted kappa = 0.71) and hearing (weighted kappa = 0.73), with differences in perception of level of severity of sensory loss. Health visitors tended to underestimate the child's functional level compared with the paediatrician. However, of 56 children classified as severely disabled by the paediatrician, 48 were classified similarly and eight as moderately disabled on the basis of the questionnaire. The end point of the trial was death or severe disability at 2 years of age. There was close similarity in the trial results whether based on the paediatric assessment or on the questionnaire. Further refinement of the questionnaire is needed, but this methodology may be useful in ascertaining the frequency of severe disability in large cohorts of babies.

Chi-Square Distribution↗
PubMed1998

Temporal relationships between hormonal and hemodynamic changes in early human pregnancy.

BACKGROUND: The systemic hemodynamic profile of human pregnancy is characterized by a decrease in mean arterial pressure, a rise in cardiac output and plasma volume in association with an increase in renal plasma flow and glomerular filtration rate. The factors and the time course responsible for the initial hemodynamic changes seen in human pregnancy have not been completely documented. We hypothesize that systemic and renal hemodynamic changes occur early, prior to the presence of the fetal-placental unit. METHODS: Thirteen women were studied prior to and immediately following conception in identical fashion at gestational weeks 6, 8, 10, 12, 24 and 36. Individuals underwent mean arterial pressure, cardiac output, inulin and PAH clearance determinations. RESULTS: Mean arterial pressure decreased by six weeks gestation (mid follicular 81.5 +/- 2.6 vs. six weeks 68.7 +/- 2.0 mm tig, P < 0.001) in association with a significant increase in cardiac output, a decrease in systemic vascular resistance and an increase in plasma volume. Renal plasma flow and glomerular filtration rate increased by six weeks gestation. Plasma renin activity and aldosterone concentration increased significantly by six weeks, whereas norepinephrine levels did not change throughout pregnancy. Atrial natriuretic peptide levels increased later, at 12 weeks gestation. Plasma cGMP levels decreased and cGMP clearance increased by six and eight weeks, respectively. CONCLUSIONS: Peripheral vasodilation occurs early in pregnancy prior to full placentation in association with renal vasodilation and activation of the renin-angiotensin-aldosterone system. Plasma volume expansion occurs early, followed later by increases in ANP concentration, suggesting that ANP increases in response to changes in intravasular volume.

Adult↗
PubMed1998

A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q.

Partial lipodystrophy (PLD), also known as "Dunnigan-Kobberling syndrome," is transmitted as a highly penetrant autosomal dominant disorder that is characterized by a dramatic absence of adipose tissue in the limbs and trunk, more evident in females than in males. In contrast, fat is retained on the face, in retro-orbital space, and at periserous sites. Associated metabolic abnormalities, including insulin resistance, hyperinsulinemia, and dyslipidemia, are referred to as "metabolic syndrome X" (Reaven 1988). Despite the intense interest in the genetic determinants underlying fat deposition, the genes involved in the lipodystrophic syndromes have not been identified. We ascertained two multigeneration families, with a combined total of 18 individuals with PLD, and performed a genomewide search. We obtained conclusive evidence for linkage of the PLD locus to microsatellite markers on chromosome 1q21 (D1S498, maximum LOD score 6.89 at recombination fraction .00), with no evidence of heterogeneity. Haplotype and multipoint analysis support the location of the PLD locus within a 21.2-cM chromosomal region that is flanked by the markers D1S2881 and D1S484. These data represent an important step in the effort to isolate and characterize the PLD gene. The identification of the gene will have important implications for the understanding of both developmental and metabolic aspects of the adipocyte and may prove useful as a single-gene model for the common metabolic disorder known as "syndrome X."

Adipose Tissue↗
PubMed1998

Antibodies to oxidized lipoproteins and their relationship to myocardial infarction.

The inflammatory process and autoimmunity in the form of antibodies to oxidized LDL are important factors in the formation of the atherosclerotic plaque. We examined the time relationship of oxidized lipoprotein antibodies to the acute oxidative stress of myocardial infarction (MI). We also examined the relationship of C-reactive protein, an index of inflammation, and therefore of free radical production, to oxidized low-density lipoprotein (LDL) antibodies. We examined five groups of patients in a cross-sectional study: group 1, within 48 h of MI; group 2, two days to 1 week; group 3, 1-4 weeks; group 4, 1-3 months; and group 5, 3-6 months post MI. Nine patients with high antibody levels were re-examined 12 months after their first assessment. Malondialdehyde (MDA)-LDL and MDA-HDL antibodies were determined by an ELISA method. The highest MDA-LDL antibodies were found within 48 h of MI, but there was no significant difference in MDA-HDL antibodies between the groups. When 9/10 patients with LDL antibodies greater than the mean of 2.7 were re-examined 1 year later, there was a significant decrease in the mean antibody levels (5.2 +/- 1.7 vs. 3.2 +/- 0.6, p < 0.02). There was no correlation between antibodies to MDA-LDL and antibodies to MDA-HDL. There was a positive correlation between serum HDL cholesterol and antibodies to MDA-LDL (r = 0.4, p < 0.02) and a positive correlation between serum triglycerides and MDA-HDL antibodies (r = 0.39, p < 0.02). Acute MI appears to be associated with significantly higher C-reactive protein and antibodies to MDA-LDL, suggesting a possible acceleration of the atherosclerotic process immediately prior to MI.

Aged↗
PubMed1998

Prostate cancer education in African American churches.

The use of churches as recruitment sites of African Americans into health promotion activities is a popular theme in the 1990s literature. This research measured the impact of previous exposure to cancer on participation in an educational program and a free prostate cancer screening. Cues to action from the Health Belief Model provided the conceptual framework. Over 500 men attended a prostate cancer educational program at their church. Men who participated in the educational program and completed the questionnaire were given a voucher that they could take to their doctor of choice for a free prostate cancer examination. Having a member of the congregation who was previously diagnosed with cancer was a significant cue to attendance at the educational program (P = 0.03). Recommendations for future cancer screening in churches are given.

Black or African American↗
PubMed1998

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains causing nosocomial outbreaks of infection in the United Kingdom.

Representative isolates from 10 distinct extended-spectrum beta-lactamase-producing strains of Klebsiella pneumoniae that caused hospital outbreaks in the United Kingdom from 1991 to 1994 were examined for relationships between their enzymes and plasmids. The beta-lactamases were identified by a combination of isoelectric focusing and gene sequencing. SHV-2 beta-lactamase was produced by isolates from four outbreaks, SHV-5 was involved in three, and SHV-4, TEM-15, and TEM-26 were involved in one outbreak each. All of the extended-spectrum beta-lactamases were encoded by self-transmissible plasmids, with sizes ranging from about 70 to 160 kb. No similarities between the restriction digest patterns of the extended-spectrum beta-lactamase-encoding plasmids were detected, except to some extent between those that produced TEM-15 and TEM-26. Thus, outbreaks of hospital infection with these organisms in the United Kingdom from 1991 to 1994 involved distinct organisms and resistance plasmids and appeared to be unrelated.

Aminoglycosides↗
PubMed1998

The contribution of low birth weight to severe vision loss in a geographically defined population.

AIMS: To describe the birthweight specific rate of severe vision loss among babies born between 1 January 1984 and 31 December 1987 to mothers resident in a geographically defined area, to classify the causes of vision loss by time of origin, and to describe the associated sensory and motor impairments and disabilities. METHODS: Cases were identified from a population register of children with early childhood impairment, which uses multiple sources of ascertainment. Further clinical information was retrieved from hospital records and by asking ophthalmologists caring for the children. RESULTS: 166 (1.25/1000 live births) children with severe vision loss diagnosed by the age of 5 years were identified. The rate among babies born weighing less than 1500 g at birth was 26 times higher than the rate for babies between 2500 g and 3499 g. These very low birthweight babies contribute 17.5% of all severely visually impaired children. Almost two thirds of children with severe vision loss have a lesion of prenatal origin. Other sensory or motor deficits are present in 69% of the children. Retinopathy of prematurity accounted for 5.4% of all visually impaired children and seven of the 166 children met the criteria for perinatal asphyxia. CONCLUSIONS: Although the contribution made by babies with a low birth weight to overall severe vision loss in the community is small, many of these children have additional impairments and probably place considerable demands on health and educational services and families. Reduction in the frequency of vision problems in the preschool population as a whole is unlikely to occur until there are major advances in the understanding of the aetiology and prevention of eye conditions of genetic, prenatal, and developmental origin.

Birth Injuries↗
PubMed1998

The feasibility of using a postal survey method to assess the health and development of 7 year old children of different birth weight.

STUDY OBJECTIVE: To test the feasibility of using a postal survey to assess health and development in 7 year old children of different birth weights and to examine the response and any resulting response bias. DESIGN: A multi-stage postal survey, using a sample stratified by birth weight. SETTING: The four counties of Oxfordshire, Buckinghamshire, Berkshire, and Northamptonshire, which make up the former Oxford NHS Region. SAMPLE: All children born in 1985 to the residents of the former Oxford region who weighed either under 1500 g or over 5000 g at birth and all those with unstated birth weight were included. Samples of approximately 130 live births were randomly selected from each 500 g birth weight band between 1500 g and 5000 g. The total sample size was 1319. METHODS: The children in the sample were identified from birth registration and traced through the National Health Service Central Register (NHSCR). Self administered questionnaires were sent through the relevant Family Health Service Authority (FHSA) and then via the child's general practitioner (GP) to the child's parent(s). When parents' permission was given, self administered questionnaires were also sent to the child's GP and teacher. MAIN RESULTS: Of the 1319 children, 1169 were alive at the age of 7 and were successfully traced. Questionnaires were forwarded by GPs to parents of 1071 children and completed questionnaires were obtained from parents of 805 children. Parents of 753 children gave permission to approach the child's teacher and replies were received for 695. Parents of 770 children gave permission to send a questionnaire to the child's GP and 724 were returned completed. Response bias was assessed for the parents' questionnaire using data recorded about all births at birth registration. Response rates varied by sex of child, social class, and country of birth of the father. In addition, parents with a child with a serious motor or sensory deficit appeared to be more likely to respond. CONCLUSIONS: Response rates at each stage of the survey were good. The bias in response to the parents' questionnaire needs to be taken into consideration in future work. The method was found to be feasible and could be applied more widely than in monitoring child health.

Birth Weight↗
PubMed1998

Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease.

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.

Age Distribution↗