Biomedical subjects
Publications and source records attributed to T O'Brien.
Fatherhood after vasectomy is rare. We describe 6 cases of DNA-proven fatherhood after vasectomy in association with persistently negative semen examination. All vasectomy patients and their partners should be counselled about the small possibility of late failure, and warning of failure should be recorded.
The Children's Atypical Development Scale (CADS) is a 53-item rating scale designed to measure unusual behaviors in children. Principal-factor analysis on a clinic-referred and pediatric sample of 474 children resulted in a four-factor solution: Communication Deficits, Lability, Social Relatedness Deficits, and Preoccupation. The CADS is internally consistent and has adequate temporal stability. CADS factor scores were differentially associated with parent and teacher rating scales, IQ, and Continuous Performance Test errors. The scale shows promise as a clinical and research tool for assessing atypical behaviors associated with pervasive developmental disorder and other neurobehavioral disorders.
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OBJECTIVE: To determine whether increased Lp(a) lipoprotein levels are associated with either non-insulin-dependent diabetes mellitus (NIDDM) or coronary artery disease (CAD) in patients with NIDDM and to examine the relationship between Lp(a) levels and glycemic control. DESIGN: We conducted a cross-sectional study of subjects with NIDDM who were participants in the Rochester Diabetic Neuropathy Study and healthy control subjects from the population of Rochester, Minnesota. MATERIAL AND METHODS: Lipids and Lp(a) lipoprotein levels were compared in 227 subjects with NIDDM and 163 control subjects and, among the subjects with NIDDM, in those with (N = 96) and without (N = 131) CAD. The correlation between Lp(a) levels and glycosylated hemoglobin was investigated. RESULTS: Subjects with NIDDM had higher triglyceride and lower high-density lipoprotein cholesterol levels than did control subjects. Subjects with NIDDM and CAD had higher total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels and lower high-density lipoprotein cholesterol levels than did subjects with NIDDM without CAD. Subjects with NIDDM had significantly higher Lp(a) levels than did control subjects, but subjects with NIDDM and CAD did not have significantly higher Lp(a) levels than did those without CAD. Among subjects with NIDDM, the level of Lp(a) was not significantly correlated with glycosylated hemoglobin. CONCLUSION: Although subjects with NIDDM have higher Lp(a) levels than do control subjects, Lp(a) does not seem to be associated with CAD in subjects with NIDDM. In this study, no association was found between Lp(a) level and glycemic control.
BACKGROUND: Nonmelanoma skin cancer (NMSC) is increasing in incidence and more are developing on the trunk and limbs. The objectives were to determine how many outpatients have more than one NMSC at the time they present for treatment and to determine the anatomical distribution of the cancers. METHODS: All outpatients with histologically confirmed NMSC visited by the authors during 1992 received a total body examination and the number and sites of NMSC were recorded. RESULTS: A total of 952 outpatients were seen. A single NMSC was present in 69.4%, two in 16%, three in 6.4%, four in 3.5%, five to nine in 4.2%, and 0.5% had ten or more. Of the 291 patients with more than one NMSC, one anatomical region was involved in 53.4%, two were involved in 38.4%, and 8.2% had three or more regions involved. CONCLUSION: Patients with NMSC required a total body examination to detect unsuspected skin cancers.
Relatively few investigations of anaerobic bacteria as ocular flora have been conducted, and their results have been contradictory. The conjunctival sacs of 22 normal subjects and of 14 patients with acquired immunodeficiency syndrome, and 22 anophthalmic sockets were cultured for anaerobic bacteria Thirty-four (77.3%) of the 44 eyes of normal subjects harbored anaerobic bacteria; Propionibacterium acnes was present in 28 eyes (63.6%), Lactobacillus species in 6 eyes (13.6%), and Veillonella species in 7 eyes (15.9%). The finding were very similar for anophthalmic sockets (p = 0.01), with 17 (77.3%) of the 22 sockets harboring anaerobes; Propionibacterium acnes was the organism identified in 16 (72.7%) of these sockets; Veillonella was identified in 4 (18.1%), Peptococcus niger in 3 (13.6%) and P. granulosum in 2 (9.0%) of these sockets. Acquired immunodeficiency syndrome patients had the highest incidence of anaerobic organisms, with positive cultures obtained from 24 (85.7%) of the 28 eyes. Propionibacterium species were isolated from 16 (57.1%) of these eyes. Clostridium species from 10 (35.7%) eyes and Actinomyces species from 8 (28.6%) eyes. It thus appears that anaerobic organisms are common flora in normal conjunctival sacs and in anophthalmic sockets, as well as in the sacs of acquired immunodeficiency syndrome patients, but the latter group had a higher incidence (x2 = 0.87) and a spectrum of organisms that was different from that of the other two groups.
In the present studies we sought to address the following questions: do chronically transplanted intrahepatic islets (IHI-Tx) secrete insulin in a coordinate pulsatile manner, and, if so, is reestablishment of this coordinate pulsatility a function of time after transplantation? We studied isolated perfused livers at 10 mM glucose from 27 rats rendered diabetic with streptozotocin and then transplanted with approximately 2 x 10(3) islets, 2 (n = 5), 7 (n = 5), 30 (n = 5), and 200 (n = 12) d after transplantation. 12 out of 12 of the 200-d IHI-Tx secreted insulin in coordinate pulses (frequency 3.9 +/- 0.3 pulses/h, amplitude 15.2 +/- 2.4 nmol/min). In contrast, one out of five 2-d, zero out of five 7-d, and one out of five 30-d IHI-Tx showed pulsatile insulin secretion. Insulin secretion was markedly greater (76 +/- 13 vs 13 +/- 3 nmol/min, P < 0.0001) in the 200-d versus early IHI-Tx. Pentobarbital 25 micrograms/ml had no effect on total (13.9 +/- 3.9 vs 15.9 +/- 3.9 nmol/min), nonpulsatile (12.9 +/- 3.5 vs 14.1 +/- 3.3 nmol/min), or pulsatile (pulse amplitude 17.6 +/- 4.5 vs 20.0 +/- 4.2 nmol/min, pulse frequency 4.1 +/- 0.3 vs 4.0 +/- 0.7 pulses/h) insulin secretion. Using synaptophysin, islet innervation was documented in 12 out of 12 200-d IHI-Tx but in none of the early IHI-Tx. We conclude that established (approximately 200 d) IHI-Tx secrete insulin in a coordinate pulsatile manner and that establishment of coordinate pulsatile insulin secretion by IHI-Tx is accompanied by increased total insulin secretion and is associated with islet reinnervation.
Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of tissues to thyroid hormone. The clinical manifestations are variable and 46-50% of children with RTH have attention deficit hyperactivity disorder (ADD). We present a new family with RTH (F120) found to have a mutation R316H in the thyroid hormone receptor beta (TR beta) gene identical for that reported in an unrelated family. Assignment of the mutant allele and haplotyping based on CA repeat polymorphism were done on 16 family members. Semistructured diagnostic interviews and psychometric testing were used to determine the psychiatric diagnosis of 12 family members by examiners blinded to the genotype. Three subjects were identified to have the R316H allele as well as mildly elevated free T4 index (168 +/- 12; normal range 77-135) and nonsuppressed TSH (4.1 +/- 1.7 mU/L). Only 2 of the subjects with RTH were found to have ADD, while one family member homozygous for the wild type TR beta and normal thyroid function tests also had ADD. Unaffected family members had higher full scale intelligence quotients (IQ) (93 +/- 7) than any of the 3 family members with RTH (77 +/- 5, p = 0.006). These data do not support the genetic linkage of ADD and RTH, but do suggest that RTH is associated with lower IQ scores that may confer a high likelihood of exhibiting ADD symptoms.
BACKGROUND: Considerable emphasis has been placed on early diagnosis and surgery for multiple endocrine neoplasia (MEN)-related medullary thyroid carcinoma (MTC) during the past two decades. Genetic screening now promises earlier and more accurate diagnosis. We examine our experience with MTC in MEN 2A and MEN 2B and assess the benefits of biochemical screening during the past 20 years. PATIENTS AND METHODS: Seventy-seven patients undergoing 63 primary total thyroidectomies and 14 reoperative procedures for MEN-related invasive MTC and/or preinvasive C-cell hyperplasia are reported. Fifty-eight patients had MEN 2A and 19 had MEN 2B; 79% of patients had a family history of MTC; 27% had pheochromocytoma, and 25% had hyperparathyroidism. RESULTS: Patients with MEN 2B had more advanced disease than those with MEN 2A, in spite of presentation at a younger age (15 years versus 24 years). Every patient with MEN 2B had invasive carcinoma, whereas 14% of patients with MEN 2A had C-cell hyperplasia without invasive disease. Nodal metastases were found less frequently in MEN 2A (14%) than MEN 2B (38%), and biochemical cure was achieved in 56% of patients with MEN 2A compared with none in patients with MEN 2B. Among patients with MEN 2A the occurrence of invasive carcinoma increased with age (p = 0.0003); 40% of patients for less than 5 years had invasive MTC compared with 100% at more than 20 years. Cause-specific mortality among patients with MEN and invasive tumors at 6, 12, and 18 years was 2%, 4%, and 7%, respectively, lower than that of patients with sporadic MTC (12%, 17%, and 23%, respectively) treated during the same time period (p = 0.028). CONCLUSIONS: Intensive biochemical screening of MEN 2 kindreds for MTC can result in detection of early disease and a significant prospect of surgical cure. Genetic testing promises additional benefits through more reliable detection of preinvasive disease, allowing prophylactic thyroidectomy in infancy. In MEN 2B, MTC is considerably more aggressive than in MEN 2A. A policy of routine thyroidectomy in infants with MEN 2B, regardless of serum calcitonin levels, is justified.
The aim of this paper is to describe a new methodology for the separation of human high-density lipoproteins (HDL) into apolipoprotein (apo) E-poor and apo E-rich subfractions by fast protein liquid chromatography (FPLC) using a heparin affinity column. Recoveries for apolipoproteins AI, AII, CI, CII, CIII, and E were 68.9, 74.7, 71.9, 73.5, 40.0, and 55.8%, respectively. We provide suggestive evidence that apo E-rich HDL is produced from apo E-poor HDL by the displacement of apo AI by apo E. Apo E-poor HDL was the predominant fraction. The molar ratio of apo E to apo AI in apo E-poor HDL was 0.02 and 0.01 for the subjects studied while in apo E-rich HDL it was 1.86 and 1.25. The molar ratios of the C apolipoproteins to apo AI are markedly different between the subfractions.
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.
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)
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.
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.
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.
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.
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.
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.