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Biomedical subjects

P C O'Brien

Publications and source records attributed to P C O'Brien.

At least 181 records · Page 10Linked to original sources
PubMed1993

Tumor necrosis factor-alpha induction by reovirus serotype 3.

We have reported previously that reovirus, when used in combination with 1,3-bis(chloroethyl)-1-nitrosourea (BCNU) chemotherapy, mediates the rejection of murine ascites tumors. Surviving animals reject a challenge with the same, but not a different, tumor, which suggests that tumor-specific immunity is induced by the treatment regimen. The present study was designed to characterize the interaction between reovirus and murine peritoneal macrophages, both in vitro and in vivo, to determine whether such a relationship may play a role in immune modulation resulting in tumor rejection. The results demonstrated that reovirus can efficiently infect peritoneal macrophages in vitro and stimulate the secretion of tumor necrosis factor-alpha (TNF-alpha). In vivo administration of reovirus, however, did not produce high levels of infection in peritoneal exudate cells, even though the cells were stimulated to express detectable levels of membrane TNF-alpha. These results suggested that infection is not necessary for TNF-alpha expression and this hypothesis was supported by the observation that this expression was also stimulated in vitro by UV-inactivated reovirus. These findings suggest that one mechanism for immune stimulation by reovirus may be through the induction of TNF-alpha.

Analysis of Variance↗
PubMed1993

Non-response bias in studies of diabetic complications: the Rochester Diabetic Neuropathy Study.

Non-response can bias studies of disease conditions but its influence has rarely been evaluated due to limitations of available data on the non-respondents. Because of a detailed medical record review for eligibility, we were able to compare clinical as well as demographic characteristics of respondents and non-respondents in a population-based study of diabetic complications among Rochester, Minnesota residents. Non-respondents were older, less well educated, more likely to be widowed and more often retired. They were much more likely to have cardiovascular disease at baseline, but the prevalence of retinopathy, nephropathy and diabetic neuropathy was similar for respondents and non-respondents, who were also comparable with regard to type of diabetes and diabetic therapy. While these findings indicate that data from the Rochester Diabetic Neuropathy Study can probably be generalized to diabetic residents generally, they reemphasize the potential for non-response bias in epidemiologic studies of clinical conditions, especially cardiovascular disease.

Age Factors↗
PubMed1993

A 50-year experience of male breast cancer: is outcome changing?

During the period 1933-1983, 124 men (median age 62.5 years, range 33-86 years) were treated for breast carcinoma. Median length of follow-up was 6.7 years and was complete for 93% of patients. Presenting complaints were most frequently a mass (95%) or pain (31%) while physical examination revealed the tumour to be central in 95% of patients with nipple or skin retraction in 36% and associated gynaecomastia in 12%. Twenty-seven per cent of the patients had a positive family history of breast cancer, 6% noted previous breast trauma and 7% had prior chest wall irradiation. Mean tumour size was 2.5 cm, and the pathological stage was 0 in 3%, I in 17%, II in 22%, III in 35%, IV in 11%, and unknown in 12%. Ninety-four per cent were ductal carcinoma. Histological grading of tumours was 2% grade 1, 10% grade 2, 33% grade 3 and 48% grade 4. Ninety-two per cent of patients underwent mastectomy (41% radical, 39% modified radical and 12% simple), while adjuvant irradiation was used in 44% and chemotherapy in 9%. Median disease-free patient survival was 5 years (36% of patients developed tumour recurrence). Median overall patient survival was 6.3 years (57% at 5 years and 31% at 10 years). Tumour size (P < 0.05), pathological stage (P < 0.04), and tumour grade (P = 0.007) were adverse factors for recurrence, while pathological stage (P < 0.02), tumour size (P < 0.03), pain (P < 0.05) and age (P < 0.02) were associated with a decreased survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Assessment of body composition with use of dual-energy x-ray absorptiometry: evaluation and comparison with other methods.

Dual-energy x-ray absorptiometry (DEXA) is a relatively new method of assessing body composition in humans. In the current study, DEXA was analyzed for accuracy and precision by using both anthropomorphic phantoms and a combination of body composition techniques in humans. Satisfactory precision for measurement of total body fat, fat-free mass, and total body bone mineral could be demonstrated in vivo and in vitro. Predictions of lean body mass in humans on the basis of DEXA, total body water, and total body potassium were significantly different. The results of multiple regression analysis suggested that a component of total body water was related to body potassium, and another component was predicted by body fat. In addition, extracellular fluid volume, as measured by the bromide space technique, was significantly associated with both fat-free mass and fat mass as measured by DEXA. These findings have implications for the interpretation of body composition data in humans.

Absorptiometry, Photon↗
PubMed1993

Alfentanil-induced epileptiform activity in patients with partial epilepsy.

We performed a retrospective study investigating the effect of alfentanil hydrochloride on electrocorticography (ECoG) in 23 patients with intractable nonlesional partial epilepsy undergoing anterior temporal lobectomies at this institution. Alfentanil is a short-acting, parenteral, opioid analgesic with a rapid onset of action. Opioid drugs have the potential to induce hippocampal electrographic seizures. Pre-excision ECoG was obtained before and after the administration of 50 micrograms/kg of alfentanil. ECoG was performed using subdural strips placed on the lateral temporal surface and in the suprasylvian region and monopolar depth electrodes implanted into the amygdala and hippocampus. The surgically excised temporal lobes revealed cortical gliosis and varying degrees of hippocampal neuronal loss in all patients. A quantitative assessment of the effect of alfentanil on the ECoG was performed by measuring the frequency of interictal spikes. There was a significant increase in the mesial temporal lobe mean spike frequency after the administration of alfentanil (p < 0.001). One patient had an alfentanil-induced mesial temporal lobe electrographic seizure. Alfentanil did not have a significant effect on spike activity in the suprasylvian region (p = 0.500). Further studies will be necessary to determine the specificity of alfentanil activation in patients with partial seizures of temporal lobe origin.

Adolescent↗
PubMed1993

Radiation therapy for early stage seminoma of the testis. Analysis of survival and gastrointestinal toxicity in patients treated with modern megavoltage techniques over 10 years.

Seventy-seven patients treated with megavoltage irradiation to the para-aortic and/or pelvic nodal areas, for stage I and non-bulky (< 5 cm) stage II seminoma of the testis, were studied at the Royal Adelaide Hospital from 1981 to 1990. The aim was not only to assess overall and relapse-free survival, but also early and late gastrointestinal toxicity in a group of patients treated in a uniform manner using modern techniques. The 10 year actuarial survival was 96.1% for all patients, being 95.6% for stage I and 100% for stage II. The 10 year actuarial complication rate for all late gastrointestinal effects was 9.1%. This consisted of a 6.5% risk of peptic ulceration and a 2.6% risk of chronic diarrhoea at 10 years. At least one acute gastrointestinal effect occurred during radiotherapy in the vast majority of patients (90.9%). Analysis of the effect of age (< or = 34 years vs > 34 years), stage (I vs II) and dose of radiation (< or = 30 Gy vs > 30 Gy), showed none of these variables to have a significant influence on overall survival or on the incidence of late complications. The results of these findings are discussed in the light of recent studies of a surveillance policy following orchidectomy for stage I seminoma of the testis. Given that gastrointestinal toxicity is the major toxicity associated with the treatment of stage I patients, the data from this study should assist clinicians and their patients to arrive at an informed decision regarding adjuvant radiotherapy.

Adult↗
PubMed1993

Ocular involvement in primary central nervous system lymphoma: an increasing clinical problem?

A case of unilateral vitreous relapse in a patient with primary central nervous system lymphoma (PCNSL) following sequential systemic chemotherapy and radiotherapy is reported. A literature review reveals that ocular involvement may occur in up to 15-25% of cases during the course of this disease. Full ophthalmological assessment, including slit lamp examination, should be included in the routine staging of PCNSL at the time of initial diagnosis and subsequently if relapse occurs.

Central Nervous System Neoplasms↗
PubMed1993

Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans.

Measurement of glucose turnover under non-steady-state conditions has proven problematic. When the mass of the glucose pool is not changing (i.e., glucose concentrations are constant) non-steady-state error can be minimized if all glucose entering the circulation has the same specific activity as plasma [radioactive infused glucose (hot-GINF) method]. Alternatively, a second tracer can be used to measure the effective volume of glucose [variable-pV method of Issekutz (T. Issekutz, R. Issekutz, and D. Elahi. (Can. J. Physiol. 52:215-224, 1974)]. To determine whether these techniques provide concordant assessments of insulin action under non-steady-state conditions, glucose turnover was measured in six subjects. After initiation of insulin (0.6 mU.kg-1 x min-1), both methods indicated similar rates of suppression of hepatic glucose release, which was complete by approximately 100-120 min. In contrast, the traditional fixed-pV method of Steele (R. Steele, J. Wall, R. DeBodo, and N. Altszuler. Am. J. Physiol. 187:15-24 1956) underestimated turnover (P < 0.01) resulting in apparent complete suppression of glucose release within approximately 40 min (P < 0.01 vs. other methods). The hot-GINF and variable-pV methods also yielded similar estimates of turnover after discontinuation of insulin. Both indicated that resumption of hepatic glucose release was slower (P < 0.01) and fall of glucose uptake faster (P < 0.01) than suggested by the fixed-pV method. Thus both the hot-GINF and variable-pV methods avoid non-steady-state error introduced by the fixed-pV method and provide concordant assessments of the rate of onset and offset of insulin action.

Adult↗
PubMed1993

C-peptide during the prolonged fast in insulinoma.

C-Peptide, a marker for insulin secretion, is purported to be elevated in patients with insulinoma but diagnostic criteria have not been established. Thirty-seven patients with histologically confirmed insulinoma studied preoperatively, 19 normal subjects, and 2 patients who subsequently acknowledged self-administration of insulin underwent the prolonged fast (< or = 72 h) according to a standard protocol. Plasma glucose, C-peptide, and insulin were measured every 6 h until plasma glucose was less than or equal to 3.3 mmol, then hourly until Whipple's triad was demonstrated or until 72 h without symptoms was reached. At the termination of the fasts, plasma was analyzed for sulfonylurea. Statistical analysis was by rank sum test. Data are expressed as median (range). The durations of fasts were 20 (2.5-68) h for patients with insulinomas and 72 h for normal subjects. At the end of fasts plasma glucose, C-peptide, and insulin concentrations were 2.2 (1.4-2.9) vs. 3.6 (2.7-5.5) mmol, P < 0.001; 0.60 (0.20-1.92) vs. 0.13 (0.07-0.43) nmol, P < 0.001; and 126 (35-840) vs. 35 (35-126) pmol, P < 0.001, respectively, for insulinoma patients and normal subjects. All plasma samples were negative for sulfonylurea. Insulinoma patients had C-peptide values at the end of the fasts greater than or equal to 0.20 nmol whereas normal subjects and patients with insulin factitial hypoglycemia had C-peptide concentrations less than or equal to 0.10 nmol when plasma glucose was less than or equal to 2.8 mmol. Insulinoma is confirmed in a sulfonylurea negative patient with Whipple's triad during the prolonged fast and a concomitant C-peptide concentration greater than or equal to 0.20 nmol.

Adolescent↗
PubMed1993

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↗
PubMed1993

Trauma and multiple sclerosis: a population-based cohort study from Olmsted County, Minnesota.

Utilizing the Olmsted County, Minnesota, population-based records-linkage resource at Mayo Clinic, we identified an incidence and a prevalence cohort with multiple sclerosis (MS), a head injury cohort, and a lumbar disk surgery cohort to evaluate the association between mechanical trauma and MS onset or exacerbation. The MS cohorts consisted of 225 incidence cases (1905 to 1991) and 164 prevalence cases (December 1, 1991) of definite MS in the population of Olmsted County. We assessed the effect of mechanical trauma in the form of spinal injury or extremity fracture with regard to precipitation of MS or exacerbation of an existing neurologic deficit. Fifty-four episodes of trauma, as defined, occurred among 39 MS prevalence cases; most occurred 10 years or more after the onset of disease and were associated with existing MS-related disability. We compared the final disability status of the groups with and without trauma. We found no correlation between the occurrence of peripheral fractures and the onset of MS, exacerbation of MS, or final disability due to MS in the prevalence cohort. In a cohort of 819 head injury cases from the Olmsted County population, none developed MS within 6 months of the trauma. In a lumber disk surgery cohort of 942 local residents, there were five with MS, but onset of MS had preceded the spinal surgery in four of the five. Thus, we found no association of head injury and spinal disk surgery with onset of MS.

Cohort Studies↗
PubMed1993

Is the incidence of dementing illness changing? A 25-year time trend study in Rochester, Minnesota (1960-1984)

We performed a time trend study of incidence of dementing illness in Rochester, Minnesota. We ascertained age- and sex-specific incidence rates for the five quinquennia, 1960 through 1984. The incidence rates sharply increased with advancing age, reaching a high of 2,922/100,000 person years in the group 85 years and older. For dementia caused either solely or predominantly by Alzheimer's disease, this figure was 2,600/100,000 person years for the oldest age group. There were no significant differences in the incidence of dementing illness between men and women. In the oldest age groups in the last two quinquennia of study, there appears to be a trend toward increasing incidence rates. Over the years, the proportion of cases attributed to dementia due to unknown causes has decreased while the proportion of cases attributed to Alzheimer's disease has increased.

Adult↗
PubMed1993

Levodopa therapy and survival in idiopathic Parkinson's disease: Olmsted County project.

We studied survival in all Olmsted County Parkinson's disease (PD) patients seen at the Mayo Clinic from 1964 to 1978, attempting to answer two questions: (1) What effect does levodopa have on survival in PD? and (2) Does the timing of levodopa administration influence survival? We chose this period because it allowed us to study patient records with a spectrum of disease durations before levodopa treatment; in many patients, the treatment delay was exclusively due to levodopa being unavailable prior to 1969. Mortality of the entire PD cohort (N = 179; 61% levodopa-treated) was greater than that of the general population (matched chronologically, geographically, and by age and gender). Lower age at onset of motor symptoms, lower Hoehn and Yahr stage at first neurologic visit for parkinsonism, and treatment with levodopa were all independent predictors of improved survival. Using a time-dependent Cox regression model, we assessed the impact of the timing of levodopa administration during the course of illness on mortality, while statistically controlling for other factors (ie, patient selection for levodopa treatment, and independent predictors of survival). Risk of death following initiation of levodopa was significantly reduced (p < 0.001), regardless of pre-levodopa duration of illness. This reduction gradually diminished over a period of 4 years on levodopa, but continued to be significantly reduced. After 4 years, increasing survival benefit again progressively accrued over time to at least 17 years of levodopa treatment (p < 0.001). At no point in time was levodopa treatment associated with increased mortality, arguing against substantial levodopa toxicity. However, despite levodopa-improved survival, mortality continues to be increased in PD relative to the general population.

Carbidopa↗
PubMed1993

The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study.

The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors.

We recently found that vibratory detection threshold is greatly influenced by the algorithm of testing. Here, we study the influence of stimulus characteristics and algorithm of testing and estimating threshold on cool (CDT), warm (WDT), and heat-pain (HPDT) detection thresholds. We show that continuously decreasing (for CDT) or increasing (for WDT) thermode temperature to the point at which cooling or warming is perceived and signaled by depressing a response key ("appearance" threshold) overestimates threshold with rapid rates of thermal change. The mean of the appearance and disappearance thresholds also does not perform well for insensitive sites and patients. Pyramidal (or flat-topped pyramidal) stimuli ranging in magnitude, in 25 steps, from near skin temperature to 9 degrees C for 10 seconds (for CDT), from near skin temperature to 45 degrees C for 10 seconds (for WDT), and from near skin temperature to 49 degrees C for 10 seconds (for HPDT) provide ideal stimuli for use in several algorithms of testing and estimating threshold. Near threshold, only the initial direction of thermal change from skin temperature is perceived, and not its return to baseline. Use of steps of stimulus intensity allows the subject or patient to take the needed time to decide whether the stimulus was felt or not (in 4, 2, and 1 stepping algorithms), or whether it occurred in stimulus interval 1 or 2 (in two-alternative forced-choice testing). Thermal thresholds were generally significantly lower with a large (10 cm2) than with a small (2.7 cm2) thermode.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗