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Biomedical subjects

A Johnson

Publications and source records attributed to A Johnson.

At least 271 records · Page 15Linked to original sources

Abdominal aortic aneurysm in the Irish population: a familial screening study.

A pilot screening programme was undertaken in Ireland to determine the incidence of abdominal aortic aneurysm (AAA) (diameter 3 cm or greater) in the siblings of 120 patients known to have AAA. There were 621 siblings; 270 of them were dead, 32 were over 80 years old and 85 lived outside Ireland, leaving 234 under 80 years of age still living in Ireland who were invited to attend for ultrasonographic screening. Of the 270 siblings who had died, 102 were women and 168 men; eight men (4.8 per cent) had died from ruptured AAA. Only 125 (53.4 percent) of the 234 siblings agreed to participate in the screening programme, 60 brothers from 31 families and 65 sisters from 35 families. Fifteen (12.0 per cent) of the 125 siblings had an AAA (median size 4.2 (range 3.1-6.8) cm), 13 (22 per cent) of the 60 male siblings and two (3 per cent) of the 65 female siblings. The prevalence of AAA among siblings was not affected by the age or sex of the patient with aneurysm. Seven of the 14 male siblings with hypertension had an AAA, compared with only six of the 46 who were normotensive (P = 0.01). The high incidence of AAA in brothers of affected patients highlights the need to counsel this group on their risk of aneurysm. The relatively low participation rate by siblings in this screening programme indicates that a hospital-based unit is unlikely to be effective in recruiting all patient siblings at risk from an AAA.

Adult↗

Study design and sample sizes for a lacI transgenic mouse mutation assay.

Design features that adjust and account for excess variation in a transgenic mouse mutation assay based on a lacI target transgene from E. coli are considered. These features include proper identification of plate, packaging reaction, and animal identifier codes throughout the experimental and analysis phases of the study, "blocking" of exposed and unexposed animals when preparing and plating multiple packaging reactions from the same genomic DNA sample, separating sectored mutant plaques and complete mutant plaques before performing any quantitative analyses, and testing for sources of excess variation attributable to features of the experimental protocol--such as plate-to-plate (within packaging reactions), packaging reaction-to-packaging reaction (within animals), and animal-to-animal (within study). Control and ethylnitrosourea-treated animal data are presented from a fully designed study in the lacI assay. The study design incorporates many of these experimental principles. Statistical methods to identify excess variability are noted, and the designed study data are used to illustrate the types of variability encountered in practice. A standard statistical test for two-sample testing is highlighted, from which recommendations are made for sample size selection in future studies.

Analysis of Variance↗

Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition.

The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 +/- 0.4 vs 1.2 +/- 0.2 mmol/l, p < 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 +/- 0.1 vs 1.9 +/- 0.3, p < 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 +/- 2.2% vs 42.4 +/- 3.4%, p < 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 +/- 68.0 vs 213.2 +/- 28.0 micrograms/mg protein, p < 0.05) and in the low-density lipoprotein as a whole (443.2 +/- 70.0 vs 340.2 +/- 28.2 micrograms/mg protein, p < 0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 +/- 7.2 vs 22.3 +/- 3.5 nmol/mg protein, p < 0.05, increased total diene formation (502 +/- 60 vs 400 +/- 30 nmol/mg protein, p < 0.05) and increased rate of diene formation (7.2 +/- 0.6 vs 5.1 +/- 0.9 nmol diene.mg protein-1.min-1, p < 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects.

Aged↗

Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia.

We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride < 2.1 mmol l-1; haemoglobin HbA1c 5.5% +/- 0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1; HbA1c 8.8% +/- 0.9%); non-diabetic subjects with serum triglycerides < 2.1 mmol l-1; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride > 2.1 mmol l-1). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d < 1.006 g ml-1). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%-15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic control subjects whose levels decreased after 2 h (P < 0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic patients (P < 0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled diabetic and non-diabetic subjects.

Alleles↗

A quality control system for the optimized sperm penetration assay.

OBJECTIVE: To develop a quality control system for the optimized sperm penetration assay (SPA) and to use this system to monitor interassay variability and stability over time. DESIGN: Four semen donors were tested consecutively for a period of weeks (7 to 139 weeks) with the SPA. Their average semen analyses and SPA scores were evaluated to monitor natural biologic variation. Intra-assay variation was obtained by dividing 11 semen samples into three aliquots and testing each separately in the SPA. A single ejaculate from seven individuals was aliquoted and frozen to be used as a control. They were tested on different assay days in 1986 and subsequently in 1991 to evaluate the assay stability over time. MAIN OUTCOME MEASURES: Results were expressed as a sperm capacitation index (mean number of sperm penetrations per ovum). RESULTS: Consecutive weekly semen analyses and SPAs on donors exhibited coefficients of variation ranging from 20% to > 40%. In contrast, these variations were much greater than intra-assay variability. Analysis of frozen semen specimens tested in several SPAs also displayed a low coefficient of variation. When aliquots of these frozen samples were tested in the SPA 5 years later, there were no differences in the observed values, showing the remarkable stability of this assay over time. The lower limit of the normal fertile range did not change over a period of 2 years. CONCLUSIONS: Results show that using fresh semen samples as a positive control in the SPA is inadequate. This deficiency has been overcome with the use of frozen semen controls. With frozen semen for quality control, the optimized SPA developed in this laboratory is a highly reproducible assay that meets the strict criteria required for clinical laboratory certification.

Animals↗

The novel fluorinated 2-nitroimidazole hypoxia probe SR-4554: reductive metabolism and semiquantitative localisation in human ovarian cancer multicellular spheroids as measured by electron energy loss spectroscopic analysis.

The novel fluorinated 2-nitroimidazole SR-4554 is undergoing preclinical development as a magnetic resonance spectroscopy and imaging probe for hypoxic tumour cells. We have used electron energy loss spectroscopic analysis (EELS) to show selective reduction and differential subcellular localisation of SR-4554 in human ovarian multicellular spheroids. SR-4554 was demonstrated to be metabolised by these A2780 cells under hypoxic but not under normal aerobic cell culture conditions. The EELS technique illustrated that the relative amount of drug within the cytoplasm of cells from both the inner region (150-160 microns from edge) and outer edge of the spheroid did not differ significantly after an initial 3 h incubation with drug. In contrast, an 8-fold differential between the amount of drug retained in the cytoplasm (primarily ribosomes and endoplasmic reticulum) of cells from the inner vs outer regions of the spheroids was observed following a subsequent 2 h 'chase' culture in drug-free medium. Within cells from the hypoxic region of the spheroid, SR-4554 was mainly associated with the endoplasmic reticulum, nucleus and the cytoplasmic side of intracellular vesicles and also to a lesser extent with the nuclear periphery. Interestingly, the drug was only weakly associated with the mitochondria and plasma membrane of the cells. The characteristics of cellular and subcellular distribution of SR-4554 are consistent with the hypothesis that 2-nitroimidazole compounds undergo hypoxia-mediated enzymatic reduction to reactive species. These reactive species are selectively retained in the cells in which they are metabolised through covalent association with subcellular components. These findings provide additional support for the clinical development of the drug as a non-invasive probe for tumour hypoxia and at the same time illustrate the utility of the EELS technique for examining the heterogeneity of drug distribution both between and within cells.

Aerobiosis↗

Patterns of care in advanced HIV disease in a tertiary treatment centre.

A retrospective chart review of all in-patient deaths in 1992 was undertaken to examine patterns of care in advanced HIV disease at St Paul's Hospital, Vancouver, Canada. St Paul's Hospital cares for approximately 75% of the Province of British Columbia's AIDS caseload. This represents about 18% of Canada's caseload. Data were collected on demographic characteristics, the utilization of home care and community services, income and social support, symptom presentation at terminal admission and the utilization of acute hospital care and hospital based palliative care. A total of 126 deaths were reviewed. All but two subjects were homosexual/bisexual men. The median age at death was 39 years (range 24-67). Four patterns of care at death were identified: (1) aggressive therapy with resuscitation 24 (19%), (resuscitation was initiated in 58%); (2) aggressive therapy with a no resuscitation order 49 (39%), in which the palliative period was a median of three days; (3) death on the palliative care unit 33 (29%), with a median survival once palliative of 20 days; and (4) death on the palliative care unit following respite admissions 16 (13%), with a median survival once palliative of 64 days. Despite a well known and respected Palliative Care Unit and community palliative care programme, there is a marked trend towards death occurring during aggressive therapy with a 200% increase in the initiation of resuscitation compared to the previous three years. No-one has been discharged alive from hospital following the initiation of resuscitation since 1988. This study illustrates the need for providers and persons infected with HIV to reconsider expectations about treatment outcomes in advanced HIV disease.

Acquired Immunodeficiency Syndrome↗

Garlic ingestion by pregnant women alters the odor of amniotic fluid.

Amniotic fluid samples were obtained from 10 pregnant women undergoing routine amniocentesis procedure. Approximately 45 min prior to the procedure, five of the women ingested placebo capsules, whereas the remaining five ingested capsules containing the essential oil of garlic. Randomly selected pairs of samples, one from a woman who ingested garlic and the other from a woman who ingested placebo capsules, were then evaluated by a sensory panel of adults. The odor of the amniotic fluid obtained from four of the five women who had ingested the garlic capsules was judged to be stronger or more like garlic than the paired samples collected from the women consuming placebo capsules. Thus, garlic ingestion by pregnant women significantly alters the odor of their amniotic fluid.

Adult↗

Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil.

Primaquine was tested as a prophylactic drug against Plasmodium falciparum in a region in western Kenya in which malaria is holoendemic. Children 9-14 years old were randomized to receive regimens of daily primaquine, daily doxycycline, daily proguanil plus weekly chloroquine, daily vitamin plus weekly mefloquine, or daily vitamin alone. Primaquine, doxycycline, and mefloquine were equally effective in preventing both symptomatic and asymptomatic malarial infections. Chloroquine plus proguanil was the least effective regimen. There was no toxicity from daily primaquine during the 11 weeks of the study. Findings show that primaquine can be successfully used as a causal prophylactic regimen against falciparum malaria in western Kenya; chloroquine plus proguanil was not as efficacious as the three other preventive regimens; most Kenyan children receiving standard doses of mefloquine and doxycycline had lower than expected serum trough drug levels; and some volunteers with adequate mefloquine or doxycycline levels at trough developed asymptomatic parasitemias and clinical malaria.

Adolescent↗

Incidence and prognostic significance of t(14;18) translocation in follicle center cell lymphoma of low and high grade. A report from southern Sweden.

BACKGROUND: The t(14;18)(q21;q32) is the most common recurrent genetic defect in follicle center cell lymphoma (FCC). Conflicting reports exist in regard to a possible prognostic significance for the translocation. PATIENTS AND METHODS: In a single center, 102 patients with either low-grade (n = 50) or high-grade (n = 52) FCC (Kiel classification) and a median follow-up of 82 months were retrospectively studied to determine survival in relation to t(14;18) as shown by either PCR of the bcl-2 rearrangement in paraffinized tissue or karyotype analysis. RESULTS: t(14;18) was detected in 30 of 50 (60%) low-grade FCC and in 12 of 52 (23%) high-grade FCC. The presence of the t(14;18) was not related to morphologic bone marrow involvement or other clinical parameters, but it was related to age: in low-grade FCC, patients with t(14;18) were an average of 17 years younger (p = 0.002) than those without the translocation. In the group with high-grade histology, 30% survived beyond 60 months regardless of t(14;18) status (p = 0.92). Patients with low-grade histology and t(14;18) fared better than those without, irrespective of age (p = 0.01). No significant difference in disease-free survival related to t(14;18) was found in either low- or high-grade FCC. CONCLUSIONS: The incidence of t(14;18) is in accord with that of other European reports. T(14;18) does not define a prognostic subset of high-grade FCC, but is significantly correlated with a better survival in low-grade FCC. The association of t(14;18) with younger age and indolent lymphoma is perplexing in light of recent findings of an age-related increase in t(14;18) in normal subjects.

Adult↗

The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly.

BACKGROUND: Reduction of GH concentrations in acromegalic subjects may improve the increased mortality associated with the condition. Audit of the biochemical outcome of the management of acromegaly is, therefore, important. OBJECTIVES: (1) To audit the biochemical 'cure' rate of acromegalic patients treated by surgery and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF-I and nadir GH during an oral glucose tolerance test. DESIGN AND MEASUREMENTS: Ascertainment of acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post-treatment GH, post-treatment IGF-I and post-treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH < 5 mU/l. Cure rates were determined. PATIENTS: Eighty-nine acromegalic patients were identified as having received surgery and/or radiotherapy. In 35/89 (39%) the most recent GH was < 5 mU/l. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (chi 2 = 7.1, 2d.f., P < 0.05). Random/basal GH showed a log-linear association with IGF-I, r = 0.72, and a linear association with nadir GH, r = 0.93. CONCLUSIONS: Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Random/basal GH measurements are useful and convenient for the audit of treatment outcome in acromegaly. Ways of improving the biochemical outcome of acromegaly should be sought.

Acromegaly↗

A service evaluation of stoma care nurses' practice.

Stoma care nurses aim to meet the physical, psychological, social and spiritual needs of patients. Development of stoma care nursing services has varied, as it has been the responsibility of each nurse, resulting in differences in the mode of delivery. This qualitative and quantitative study involved stoma care nurses from six areas in Essex, to assess patient perception of the service they received. Overall, the satisfaction level was high despite differences in delivery of care especially timing and frequency of visits at home.

Adolescent↗

Assessing the contribution of birth asphyxia to cerebral palsy in term singletons.

In a geographically-based study, we investigated the risk of cerebral palsy following intrapartum asphyxia at term, and the contribution of intrapartum asphyxia at term to the overall rate of cerebral palsy. We used stringent criteria for identifying intrapartum asphyxia, while recognising that the initial hypoxial insult might have occurred in the antenatal period. In the first part of the investigation, a cohort of 160 term, singleton infants, with a low (< or = 3) 1-minute Apgar score, was followed to the age of 5 years. Six infants in the cohort had presumed intrapartum asphyxia, of whom two died in the neonatal period, three had spastic quadriparesis, profound developmental delay and visual impairment, and one was unimpaired. The frequency of cerebral palsy associated with birth asphyxia was estimated as one in 3700 full-term livebirths. To assess the impact of birth asphyxia on the overall rate of cerebral palsy, all cases of cerebral palsy born in the study period were identified. Of the 30 cases, the three identified in the follow-up study were the only ones whose impairment could be attributed to birth asphyxia in a full-term birth. Birth asphyxia at term therefore was associated with 10% [95% confidence interval (CI) 2.1, 26.5] of all cases of cerebral palsy and with 20% (95% CI 4.3, 48.1) of the 15 cases of cerebral palsy in children born at term.

Apgar Score↗

Influence of halothane-diethyl-ether azeotrope and isoflurane on ventilation. Re-evaluation of an obsolete drug.

The azeotropic mixture of halothane and diethyl-ether has been claimed to be a suitable anaesthetic agent for use during difficult conditions because of its negligible effect on circulation and ventilation. The purpose was to evaluate the effect of halothane-diethyl-ether azeotrope (HE) and isoflurane (ISO) on ventilation. 12 patients scheduled to undergo minor orthopaedic surgery and belonging to ASA 1, were randomly allocated to the HE group or the ISO group. Evaluation of resting ventilation and ventilation stimulated by hypercarbia and hypoxaemia was done on three occasions: (A) before anaesthesia, (B) after inhalational induction of anaesthesia and intubation without muscle relaxants when the level of anaesthesia was 1 MAC and (C) half an hour after operation and during recovery. Resting ventilation and the ventilatory response to hypercarbia during anaesthesia were maintained in the HE group but not in the ISO group, whereas the ventilatory response to hypoxaemia during anaesthesia was absent in both groups. The responses had returned to normal values in both groups during recovery. We conclude that halothane-diethyl-ether azeotrope is comparatively safe during anaesthesia with spontaneous breathing provided arterial oxygenation is adequate. This makes this azeotrope suitable for use by anaesthetists with limited experience and during difficult conditions such as civil disaster or war.

Adolescent↗

HIV-related non-Hodgkin's lymphoma among European AIDS patients. AIDS in Europe Study Group. AIDS in Europe Study Group.

The epidemiology of HIV associated non-Hodgkin's lymphoma (NHL) was investigated in 6550 European patients with AIDS. NHL was diagnosed in 3.5% of all patients at the time of the AIDS diagnosis. Although the probability of being diagnosed with NHL at AIDS diagnosis was significantly higher among intravenous drug users than among homosexual men, and was associated with increasing age, the observed incidences of NHL were more strikingly similar than any differences. The rate of developing NHL after a previous AIDS diagnosis was 2.4 per 100 patient years of follow-up, and remained constant during a 5-year follow-up period. While primary brain lymphomas comprised only 9% of NHL diagnosed at the time of AIDS, they comprised 38% of NHL diagnosed after AIDS (p < 0.001). The prognosis for patients with NHL at AIDS diagnosis was poor with a median survival of 5 months. A diagnosis of primary brain lymphoma was uniformly associated with a poor outcome. It is concluded that the probability of developing NHL in late stage HIV infection is lower than previously anticipated from the results of small studies on patients receiving long-term anti-retroviral therapy.

Acquired Immunodeficiency Syndrome↗

Model to identify potentially preventable cerebral palsy of intrapartum origin.

A six stage model was applied to a geographically defined population of 210 singleton children born at term who had a diagnosis of cerebral palsy at 5 years of age. Thirty five children were identified as those most likely to have cerebral palsy of intrapartum origin; in 26 of these there was evidence of suboptimal care. It is suggested that this simple model should be tested on populations of children with cerebral palsy and the underlying principles used when considering the likely cause of cerebral palsy in individual children.

Birth Injuries↗