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Biomedical subjects

T O'Brien

Publications and source records attributed to T O'Brien.

At least 145 records · Page 8Linked to original sources

Victims of our climate.

In order to test the hypothesis that the volume of paediatric orthopaedic trauma is related to the weather, we analysed all children with fractures admitted to our unit over a 3-year period and correlated this information with local meteorological data. The average number of children admitted per month with fractures showed a strong positive correlation with mean monthly sunshine hours (Pearson correlation coefficient 0.91) and a weak negative correlation with mean monthly rainfall (-0.24). The summer peak in the incidence of fractures persisted when the effect of school holidays was eliminated. Fractures involving the radius accounted for 48.7 per cent of all fracture admissions and correlation with sunshine hours was highest in this group. Almost two-thirds of all fracture admissions were male and these had a slightly higher mean age (8.2 years) than females (7.6 years). This data has implications for bed management and staffing levels in a paediatric orthopaedic unit.

Adolescent↗

Hypertension and dyslipidemia in patients with insulinoma.

Hyperinsulinemia is alleged to contribute to the pathogenesis of hypertension and dyslipidemia (hypertriglyceridemia) in the setting of insulin resistance. To assess the association among hyperinsulinemia, hypertension, and hypertriglyceridemia in the absence of insulin resistance, we determined their prevalence in a large cohort of patients with insulinoma (N = 250). In this retrospective case-control study, patients with insulinoma were matched by age, gender, race, and year of operation with 217 control patients admitted to the hospital for elective cholecystectomy. Mean preoperative blood pressure measurements were compared between study patients and control patients. In addition, age-, gender-, and race-specific percentiles of blood pressure were compared with data from the National Health and Nutrition Examination Survey I, and those of triglycerides (N = 65) and cholesterol (N = 70) were compared with Mayo Clinic normal reference data. The study group consisted of 105 men and 145 women; the median age was 41 years (range, 8 to 82). The median duration of symptoms before operation was 1.9 years (range, 0.05 to 40 years). After adjustment for body mass index, no statistically significant differences in systolic and diastolic blood pressure were noted between patients with insulinoma and matched control patients (131 +/- 19 versus 128 +/- 18 mm Hg and 81 +/- 11 versus 79 +/- 9 mm Hg, respectively). No relationship was observed between duration of hyperinsulinemia (as long as 40 years) and blood pressure. The age- and gender-specific percentiles of systolic and diastolic blood pressure of the patients with insulinoma did not differ from the age- and gender-specific percentiles for the general white population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Apolipoprotein A-II levels and coronary artery disease in subjects with and without diabetes: a study with use of a specific radioimmunoassay for apolipoprotein A-II.

High-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, and apo A-II levels were measured in 1,219 normal subjects with no clinical evidence of coronary artery disease, 81 subjects without diabetes but with "significant" coronary artery disease determined by coronary arteriography, and 151 subjects with non-insulin-dependent diabetes mellitus (48 with clinical coronary artery disease and 103 without such disease). In the normal subjects, apo A-II levels were less influenced by age, gender, and use of medications than were apo A-I or HDL-C levels. HDL-C, apo A-I, and apo A-II levels were significantly lower in subjects who had coronary artery disease with or without diabetes than in control subjects. After adjustments were made for age and sex, however, apo A-II levels were no longer significantly different between subjects with diabetes who had and those who did not have coronary artery disease. In subjects without diabetes, apo A-II may provide some advantages over apo A-I and HDL-C in the assessment of risk of coronary artery disease because it is influenced less by age, gender, and medications. In subjects with diabetes, however, apo A-II levels are similar in the presence or absence of coronary artery disease.

Adrenergic beta-Antagonists↗

Hyperlipidemia in patients with primary and secondary hypothyroidism.

Hypothyroidism is associated with an increased risk of coronary artery disease. This observation may in part be related to the lipid abnormalities in patients with this condition. The lipid profiles of 268 patients with primary hypothyroidism and 27 with secondary hypothyroidism, who were examined in the Thyroid Clinic at the Mayo Clinic during a 1-year period, were reviewed. Hyperlipidemia was commonly associated with both primary and secondary hypothyroidism. The lipid values decreased with treatment of hypothyroidism. Type IIa hyperlipidemia was the most common lipid abnormality in patients with primary hypothyroidism, whereas type IIb was the most common in those with secondary hypothyroidism. Total/high-density lipoprotein cholesterol and low-density lipoprotein/high-density lipoprotein cholesterol ratios were increased in both male and female patients with primary and secondary hypothyroidism, and they decreased with restitution of the euthyroid state, although this decrease achieved statistical significance only in female patients. Significant associations with total thyroxine were noted for total cholesterol and triglycerides and with thyroid-stimulating hormone (thyrotropin) for total cholesterol and low-density lipoprotein cholesterol. Thus, both primary and secondary hypothyroidism are commonly associated with an atherogenic lipid profile, which improves with replacement of thyroid hormone. Even after restitution of the euthyroid state, however, the lipid profile remains atherogenic in male patients. In comparison with primary hypothyroidism, the lipid profile is more atherogenic in secondary hypothyroidism because of the lower high-density lipoprotein cholesterol levels associated with this condition.

Adolescent↗

Rapid changes in Drosophila transcription after an instantaneous heat shock.

Heat shock rapidly activates expression of some genes and represses others. The kinetics of changes in RNA polymerase distribution on heat shock-modulated genes provides a framework for evaluating the mechanisms of activation and repression of transcription. Here, using two methods, we examined the changes in RNA polymerase II association on a set of Drosophila genes at 30-s intervals following an instantaneous heat shock. In the first method, Drosophila Schneider line 2 cells were quickly frozen to halt transcription, and polymerase distribution was analyzed by a nuclear run-on assay. RNA polymerase transcription at the 5' end of the hsp70 gene could be detected within 30 to 60 s of induction, and by 120 s the first wave of polymerase could already be detected near the 3' end of the gene. A similar rapid induction was found for the small heat shock genes (hsp22, hsp23, hsp26, and hsp27). In contrast to this rapid activation, transcription of the histone H1 gene was found to be rapidly repressed, with transcription reduced by approximately 90% within 300 s of heat shock. Similar results were obtained by an in vivo UV cross-linking assay. In this second method, cell samples removed at 30-s intervals were irradiated with 40-microseconds bursts of UV light from a Xenon flash lamp, and the distribution of polymerase was examined by precipitating UV cross-linked protein-DNA complexes with an antibody to RNA polymerase II. Both approaches also showed the in vivo rate of movement of the first wave of RNA polymerase through the hsp70 gene to be approximately 1.2 kb/min.

Animals↗

Palliative care and taboos within motor neurone disease.

Taboos, whether held by professional carers, patients or families have the capacity to influence a whole range of choices that must be made during the course of any illness. In the case of motor neurone disease, decisions regarding if, when and how to break bad news, the place of care (home, hospital or hospice), the introduction of aids and devices, and, ultimately, choices regarding the place of death, will all be influenced by a range of taboos. If professional carers have major unresolved issues concerning their own mortality, it is unlikely that they will be able to truly stand alongside those who are facing their own imminent death. In discussing taboos, essentially what is of concern is attitudes. A basic change in attitudes is required if we are to stop viewing patients with incurable illness as some kind of medical failure.

Amyotrophic Lateral Sclerosis↗

Insulin surrogates in insulinoma.

Universally accepted criteria for relative hyperinsulinemia have not been established for the diagnosis of insulinoma. Therefore, we sought measures of insulin action which might act as surrogates for insulin measurements and thereby contribute to the assessment of hyperinsulinemia. Since insulin is antilipolytic, antiketogenic, and glycogenic we measured plasma beta-hydroxybutyrate, FFA, and the response of plasma glucose to iv glucagon at the end of the prolonged fast in 40 patients, later confirmed histologically to have insulinoma and 25 normal persons. Plasma beta-hydroxybutyrate and FFA concentrations were significantly lower in the patients with insulinoma (median, range), (0.3, 0.1-2.7 vs. 4.5, 1.2-7.0 mmol, P < 0.0001, and 1.03, 0.17-1.75 vs. 1.79, 1.17-3.12 mmol, P < 0.001, respectively), whereas the responses of plasma glucose to glucagon were significantly greater (3.0, 1.4-5.4 vs. 0.7, 0.0-1.3 mmol, P < 0.001) than in the normals. For patients with insulinoma (20/40) and normal subjects (13/25) with plasma glucose less than or equal to 3.3 mmol and plasma insulin and C-peptide concentrations in the normal overnight fasting range, conditions in which hyperinsulinemia is most difficult to assess, a clear distinction was provided by plasma glucose response to glucagon and plasma beta-hydroxybutyrate but not by plasma FFA, plasma insulin, nor plasma C-peptide. We conclude that plasma glucose response to iv glucagon greater than or equal to 1.4 mmol and plasma beta-hydroxybutyrate less than or equal to 2.7 mmol, at the end of the prolonged fast are indicative of hyperinsulinemia of insulinoma when the plasma glucose is less than or equal to 3.3 mmol. In this plasma glucose range these insulin surrogates provide better diagnostic accuracy than plasma insulin and C-peptide.

3-Hydroxybutyric Acid↗

Lipoprotein compositional changes in the fasting and postprandial state on a high-carbohydrate low-fat and a high-fat diet in subjects with noninsulin-dependent diabetes mellitus.

Our aims were 1) to examine the effects of a high-carbohydrate low-fat diet on fasting and postprandial plasma lipids, apolipoproteins (apo), and lipoprotein composition in noninsulin-dependent diabetes mellitus, and 2) to determine whether postprandial shift of apo between triglyceride-rich lipoproteins (TRLP) and high density lipoproteins (HDL) is affected by diet. A cross-over study, of 4 weeks duration, of a high-carbohydrate (60% carbohydrate, 20% fat) and a high-fat (40% carbohydrate, 40% fat) diet was performed in seven subjects with noninsulin-dependent diabetes mellitus. TRLP, low density lipoproteins (LDL), and HDL were separated by fast protein liquid chromatography. The high-carbohydrate diet resulted in a decrease of fasting total, HDL, and LDL cholesterol and a trend toward an increase in plasma triglycerides. The apo composition of fasting TRLP and HDL was similar on both diets. TRLP apo CII, CIII, and E increased whereas HDL apo CII, CIII, and E decreased postprandially on both diets. In contrast, TRLP apo CI increased, and HDL apo CI decreased only after the high-carbohydrate diet. We conclude that 1) a high carbohydrate diet results in a decrease in total, LDL, and HDL cholesterol and a trend toward an increase in plasma triglycerides; 2) fasting TRLP and HDL apo composition was similar on a high-carbohydrate or a high-fat diet; and 3) on both diets, apo CII, CIII, and E transfer from HDL to TRLP postprandially. However, only the high-carbohydrate diet induced postprandial transfer of apo CI from HDL to TRLP. This may explain in part the changes in lipoproteins observed with this diet.

Aged↗

Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases.

Generalised ventricular dilatation with or without cerebral atrophy is common in longstanding multiple sclerosis. This has been widely assumed to be due to periventricular white matter atrophy rather than true communicating hydrocephalus although it can be difficult to distinguish between these on radiological grounds. Here we report 2 chronic MS patients who had progressive dementia, gait disturbance and urinary incontinence and in whom neuroimaging, and in one case CSF infusion studies, suggested hydrocephalus. Both significantly improved following shunting procedures. We suggest that further study is required to investigate whether a significant proportion of patients with chronic MS and dilated ventricles have shunt-responsive hydrocephalus.

Cerebrospinal Fluid Shunts↗

Surgical management of primary hyperparathyroidism in multiple endocrine neoplasia types 1 and 2.

BACKGROUND: The surgical management of primary hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) remains controversial. In addition, the rarity of MEN 2A-related hyperparathyroidism has not allowed for a separate strategy for this condition. This study examines our surgical experience with MEN 1- and MEN 2A-related hyperparathyroidism and attempts to define a rational therapeutic approach to each. METHODS: Between 1970 and 1991, 124 patients underwent surgery for MEN-related hyperparathyroidism at our institution. Primary cervical explorations were performed in 84 patients with MEN 1 and 18 with MEN 2A. An additional 22 patients with MEN 1 underwent reoperative surgery. All patients with MEN 2A underwent concomitant thyroidectomy for medullary thyroid cancer. RESULTS: Compared with patients with MEN 1, patients with MEN 2A, had a lower preoperative serum Ca2+ level and fewer symptoms or complications of hypercalcemia. Multiple gland disease was evident in 90% and 83%, respectively, of patients with MEN 1 and MEN 2A. Primary explorations in patients with MEN 1 resulted in surgical cure in 94%, persistent hypercalcemia occurring in no patient undergoing subtotal resection compared with 17% of patients in whom more conservative resections were performed (p = 0.005). In patients with MEN 1, 10-year recurrence of hypercalcemia was 16% for primary explorations and 30% for reoperative procedures. In contrast, all patients with MEN 2A, whether treated by total, subtotal, or lesser resections, were cured after surgery and none had recurrence during a median follow-up of 5.8 years. CONCLUSIONS: In MEN 1 the surgical principles should be (1) identification of all four glands, (2) subtotal resection to ensure cure and facilitate possible reoperation, and (3) excision of supernumerary thymic glands. In MEN 2A we should identify and resect all enlarged glands for cure, but routine subtotal resection need not be performed because this condition is readily cured and recurrence is rare.

Adolescent↗

Familial occurrence of multiple nonmelanoma skin cancer.

A survey of patients with histologically confirmed nonmelanoma skin cancer (NMSC) found 12 families in which several members developed skin cancers. The prevalence of NMSC in these families was far greater than in the normal population. The trait appeared to be dominantly inherited, and NMSC developed at an earlier age in succeeding generations, possibly because of a change in sun exposure habits.

Adolescent↗

Basal-cell carcinoma in temperate and tropical Australia.

The clinical features of patients with basal-cell carcinoma (BCC) living in temperate and tropical Australia were studied. In the temperate zone the patients were considerably older on average, men outnumbered women and there were differences between the sexes in the site of the prevalent BCC. In the tropics the patients were significantly younger on average, the male-to-female ratio approached unity and there were no differences between the sexes with regard to the site of the BCC.

Adult↗

Motor neurone disease: a hospice perspective.

OBJECTIVE: To describe and evaluate the management of patients with motor neurone disease from the perspective of a hospice. DESIGN: Retrospective analysis of hospice medical and nursing notes. SETTING: Established 62 bed teaching and research hospice. SUBJECTS: 124 patients with motor neurone disease cared for by the hospice between January 1980 and November 1990. MAIN OUTCOME MEASURES: Patient profile; functional status; symptom control and use of opioids; insight; mode and management of death. RESULTS: 124 patients (67 women, 57 men) had a mean age 63.9 years. The median length of admission was 61.5 days (range 1 to 2147). 84 patients (68%) were aware of their diagnosis and its implications when first seen by a hospice doctor. Functionally, the patients were very dependent. Symptoms such as pain, dyspnoea, and insomnia were major problems that responded well to opioids. Many patients were noted to deteriorate "suddenly," and in 58% of cases death occurred within 24 hours of this deterioration. When dying, 106 patients (94%) were peaceful and settled. 101 patients (89%) received opioids during this dying period. No patient chocked to death. CONCLUSIONS: Although motor neurone disease is an uncommon disorder, many of its symptoms occur commonly in medical practice and must be actively treated. Opioids are both safe and effective for such treatment. The term chocking is both inaccurate and inappropriate in describing the cause of death in motor neurone disease and its use should be abandoned.

Adult↗

Prosthetic vascular graft infection.

The aetiology, diagnosis and management of prosthetic vascular graft infection are reviewed. The importance of contamination at the time of surgery as the crucial aetiological factor is highlighted. Staphylococcus epidermidis is the causative organism in over 50 per cent of cases and the reasons for this are explored. Sound surgical technique, use of prophylactic antibiotics and the avoidance of a groin incision are emphasized as the most important factors in prevention of graft infection. Difficulties of diagnosis are highlighted and the diagnostic role of various imaging methods is assessed. Graft excision with extra-anatomic revascularization is presented as the conventional surgical solution, while the roles of less radical surgical solutions and non-operative management are discussed.

Blood Vessel Prosthesis↗

Serum ferritin in newly diagnosed and poorly controlled diabetes mellitus.

Serum ferritin was measured in 50 patients at diagnosis of diabetes mellitus (DM) and in 20 patients with established DM and poor metabolic control. Twenty-two patients had hyperferritinemia at diagnosis. Four patients had a recognised cause for their hyperferritinemia. In the remaining 18 patients ferritin levels decreased from a mean of 506 +/- 3.6 (SE) ug/l at diagnosis to 254 +/- 29.2 ug/l seven months later (p < 0.001). Metabolic control improved significantly over the same time. All 20 patients with established DM and poor metabolic control had normal ferritin levels. When compared with the newly diagnosed hyperferritinemic patients no difference was found in levels of glycosylated haemoglobin, but ferritin values differed significantly between the two groups (p < 0.001). These results indicate that transient hyperferritinemia is a feature of newly diagnosed DM but not of established DM with poor control. If used to screen diabetic patients for haemochromatosis, serum ferritin should be measured in established DM rather than at diagnosis.

Adolescent↗

Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E-rich very low density lipoprotein fraction.

To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.

Adult↗

Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin.

We report the occurrence of cytopenia and hypothyroxinemia attributed to decreased levels of thyroxine-binding globulin in patients receiving nicotinic acid. We describe two patients in whom hypothyroxinemia developed while they were taking nicotinic acid; these patients also had decreased levels of thyroxine-binding globulin. Results of all thyroid function tests returned to normal when use of the nicotinic acid was discontinued. In one patient, leukopenia and thrombocytopenia developed during nicotinic acid therapy alone. These conditions were reversed after the drug regimen was discontinued. In another patient, leukopenia and thrombocytopenia developed during combination nicotinic acid and lovastatin therapy. When administration of both drugs was discontinued, the hematologic abnormalities, which could have been due to either nicotinic acid or lovastatin, diminished. We suggest that cytopenia may develop in patients receiving nicotinic acid; thus, thyroid function tests should be interpreted in light of a possible decreased level of thyroxine-binding globulin.

Aged↗