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Biomedical subjects

P C O'Brien

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

At least 217 records · Page 12Linked to original sources
PubMed1991

Persistence of Theiler's virus infection following promotion of central nervous system remyelination.

Chronic infection of SJL/J mice with the Daniel's strain of Theiler's virus develop primary demyelination, viral persistence but minimal central nervous system (CNS)-type remyelination. In contrast, treatment of virus-infected mice with sera or immunoglobulin G (IgG) from mice immunized with homogenized spinal cord (SCH) emulsified in incomplete Freund's adjuvant promotes CNS remyelination. We measured levels of infectious virus, virus antigen and virus-specific antibody to determine if treatments which promote CNS remyelination are able to modulate infection. Levels of virus-specific antibody were higher in mice treated with SCH/IgG than control treatment groups and correlated positively with extent of remyelination. Although number of virus antigen-positive cells in spinal cord was less in mice treated with SCH/IgG than mice treated with phosphate buffered saline (PBS)/IgG, there was only a slight negative correlation with extent of remyelination by regression analysis. Titers of infectious virus isolated three to six months following infection were not different among treatment groups. Even though treatment of mice with SCH/IgG reduced number of virus antigen-positive cells and enhanced levels of virus-specific antibody, CNS remyelination can occur despite presence of infectious virus.

Animals↗
PubMed1991

Pseudorabies virus-induced suppression of major histocompatibility complex class I antigen expression.

The ability of pseudorabies virus (PrV) to down-modulate expression of major histocompatibility complex class I antigens in murine and porcine cells was investigated. When quantified by flow cytometry, surface expression of class I Kk and Dk antigens on PrV-infected cells decreased by 60% or more. Down-modulation was associated with a decrease in total cellular class I antigens, indicating regulation at the transcriptional or posttranscriptional level. PrV did not suppress expression of transferrin receptor, suggesting a selective regulatory mechanism.

Animals↗
PubMed1991

Psychologic and adaptational difficulties anteceding amyotrophic lateral sclerosis: Rochester, Minnesota, 1925-1987.

Comprehensive medical records of 45 amyotrophic lateral sclerosis (ALS) patients and 90 controls from the same community, matched by age, gender, and period of observation, were reviewed. Three (13%) of 23 men with ALS, 15 (33%) of 46 control men, 10 (45%) of 22 women with ALS, and 19 (43%) of 44 control women had antecedent psychologic or adaptational difficulties. The proportions of long-standing or serious conditions were comparable in all four groups. However, no man in whom ALS developed had a record of mild antecedent difficulties alone, whereas 3 would have been expected (p = 0.024).

Adaptation, Psychological↗
PubMed1991

Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis.

We reviewed the medical records of 821 Olmsted County residents who had suffered head trauma with presumed brain injury between 1935 and 1974 and were more than 40 years old at the time of their last medical assessment. These patients were followed over 15,000 person-years for dementia and other degenerative neurologic diseases. The standardized morbidity ratio (SMR) for dementia was 1.06, and the SMR for dementia of the Alzheimer type was 1.00. These values are not significantly elevated and are inconsistent with studies that suggest that head trauma is a risk factor for Alzheimer's disease. In addition, the SMRs for parkinsonism (1.04), Parkinson's disease (0.94), and amyotrophic lateral sclerosis (1.05) were not significantly elevated, providing no evidence that head trauma is a risk factor for these disorders. However, these latter results are based on smaller total case numbers.

Alzheimer Disease↗
PubMed1991

When is an apparent excess of neurologic cases epidemiologically significant?

To conserve clinical and public health resources, it is necessary to screen reports from the community of an excess or cluster of cases of chronic neurologic diseases for potential epidemiologic significance, ie, to identify those clusters that may have occurred owing to the operation of an underlying etiologic cause rather than to chance alone. Traditionally, the probability that such a cluster has occurred by chance within the reporting community is computed, ignoring the fact that many other similar communities have not reported a cluster. We propose a modified approach that takes this larger universe of communities into account, thereby raising the threshold for potential epidemiologic significance. As a result, the lowest value for the ratio of observed-to-expected cases that may be considered of epidemiologic significance should be increased by factors of 2 for small clusters (one to three expected cases), 1.5 for intermediate clusters (seven to 30 expected cases), and 1.3 for large clusters (60 to 90 expected cases). Consequently, case ascertainment and full field investigations can be reserved for only those reports that, if confirmed, would represent a cluster not due to chance alone. We illustrate this with a case from our own experience.

Amyotrophic Lateral Sclerosis↗
PubMed1991

The Rochester Diabetic Neuropathy Study: design, criteria for types of neuropathy, selection bias, and reproducibility of neuropathic tests.

A cross-sectional survey and subsequent longitudinal study among diabetic residents of Rochester, MN--The Rochester Diabetic Neuropathy Study (RDNS)--is population-based and uses quantitative, validated, and unique end points to detect, classify, and stage neuropathy. Nondiabetic persons, drawn from the same population, serve as controls. For patients 10 to 70 years old, the RDNS cohort is representative of diabetics living in Rochester, MN. We assessed reproducibility of tests used to characterize and quantitate severity of neuropathy in 20 diabetic subjects without neuropathy and with varying severities of neuropathy. Using intraclass correlation coefficient (rI) as a measure of test reproducibility, we found high rI (usually 0.9 or better) with small confidence intervals for the Neurologic Disability Score (NDS); weakness subset of NDS (W-NDS); vibratory and cooling detection thresholds (using computer-assisted sensory examination [CASE] IV); compound muscle action potentials; sensory nerve action potentials; and motor nerve conduction velocities. There was good agreement among three trained observers for NDS and the W-NDS.

Action Potentials↗
PubMed1991

Epidemiologic correlates of sporadic amyotrophic lateral sclerosis.

We evaluated 74 selected patients with amyotrophic lateral sclerosis (ALS) and 201 matched controls for risk factors for ALS by a case-control design and a sequential questionnaire/interview technique to quantitate biographic data. We analyzed occupational and recreational data only for 47 male patients and 47 corresponding patient controls; data for women were insufficient. We used nonparametric analyses to evaluate five primary comparisons of ALS patients with controls: (1) more hard physical labor, p not significant (NS); (2) greater frequency of neurodegenerative disease in family members, p NS; (3) greater exposure to lead, p less than 0.05; (4) more years lived in a rural community, p NS; and (5) more trauma or major surgery, p NS. Men with ALS had worked more frequently at blue-collar jobs (although not a statistically significant difference, p = 0.10) and at welding or soldering (p less than 0.01). These results suggest that there may be an association between ALS in men and exposure to lead vapor. The limited nature of the association favors a multifactorial etiologic mechanism of ALS.

Adult↗
PubMed1990

Evaluation of unfavorable histologic subtypes in endometrial adenocarcinoma.

A retrospective review of 388 patients who presented to the Mayo Clinic for treatment of endometrial carcinoma between 1979 and 1983 was performed and the surgical and pathologic observations were documented. An uncommon histologic subtype was detected in 52 patients (13%): 20 adenosquamous, 14 serous papillary, 11 clear cell, 7 undifferentiated. In contrast to the survival of patients with endometrioid lesions (92%), the overall survival in these patients was only 33%. Each of the individual abnormal histologic subtypes exhibited a survival of less than 50%. At the time of surgical staging, 62% of patients with unfavorable histologic subtypes had extrauterine spread of disease. Despite liberal utilization of postoperative adjuvant therapy in 42 of the 52 patients (81%), only 10% of these patients survived 5 years. Fifty-five percent had a component of recurrence outside of the abdominal/pelvic cavity. Subsequent treatment considerations should incorporate regimens addressing systemic and local tissue control.

Adenocarcinoma↗
PubMed1990

Cutaneous malignant melanoma in Rochester, Minnesota: trends in incidence and survivorship, 1950 through 1985.

In Rochester, Minnesota, 107 incidence cases of cutaneous malignant melanoma (in 46 male and 61 female patients) were diagnosed during the years 1950 through 1985. Overall crude incidence rates were 6.0 and 6.6 per 100,000 males and females, respectively. Evaluation of trends in 9-year periods showed that the rates increased from 3.2 to 8.9 for males (P = 0.015) and from 4.4 to 11.7 for females (P less than 0.001). Age-specific rates suggested that the highest incidence occurs in the age-groups 50 to 59 years and 70 years or older for males and 40 to 49 years and 70 years or older for females. Lesions were most common in the head and neck area among males (P = 0.044) and on the lower extremities among females (P = 0.018). The most frequent histologic type was superficial spreading melanoma (61%). Five-year survival was diminished overall for patients with cutaneous malignant melanoma--0.72 in comparison with 0.88 expected for the general population. Statistically significant risk factors for survival were depth of invasion of the lesion (Clark level), thickness of the lesion, histologic type, and age of the patient.

Adult↗
PubMed1990

Long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B: a prospective, randomized treatment trial.

We conducted a prospective, randomized trial to study the efficacy and tolerance of long-term versus short-term treatment with recombinant interferon alfa-2a in patients with chronic hepatitis B. Ten patients were randomly assigned to a 6-month interferon regimen, and 10 patients were assigned to a 3-week interferon trial. Eleven patients (five assigned to long-term treatment and six to short-term treatment) did not complete interferon therapy: eight had either severe thrombocytopenia or neutropenia; one had pronounced fatigue in relationship to administration of interferon; one had spontaneous bacterial peritonitis and sepsis and died; and one had a massive fatal variceal hemorrhage during interferon therapy. Most of the serious hematologic complications occurred in patients with cirrhosis and hypersplenism. In one patient, seroconversion to hepatitis B virus DNA negativity occurred before the onset of treatment. Four of the five patients able to complete the 6-month interferon regimen and only one of four patients able to complete the 3-week trial had seroconversion to hepatitis B virus DNA negativity. Thus, we conclude that the therapeutic response was better among patients who were able to complete a 6-month interferon trial. In patients with cirrhosis and hypersplenism, development of either severe thrombocytopenia or leukopenia associated with interferon therapy precluded completion of treatment.

Adult↗
PubMed1990

Parathyroid hormone-related peptide in lactation and in umbilical cord blood.

Parathyroid hormone-related peptide (PTHrP) is expressed in lactating rat mammary glands after suckling, as a result of increases in prolactin rather than suckling per se. In addition, PTHrP produced in the fetal parathyroid glands and placenta may be responsible for stimulation of placental calcium transport. In the current study, we used a radioimmunoassay for human PTHrP to measure levels of the peptide in (1) human breast milk, cow's milk, and two infant formulas; (2) sequential plasma samples in prepartum and postpartum lactating women; (3) women with pathologic hyperprolactinemia; and (4) human umbilical cord blood. In normal subjects, plasma PTHrP levels ranged from less than 2 to 5 pmol/liter. In contrast, human breast milk contained substantially increased levels of immunoreactive PTHrP. Similar elevations were found in cow's milk and in one infant formula. Column chromatography of breast milk demonstrated that PTHrP immunoreactivity included a region of adenylate cyclase stimulating activity, consistent with the presence of biologically active PTHrP. Plasma prepartum PTHrP values did not differ from corresponding postpartum values in lactating women. Women with hyperprolactinemia had a mean plasma PTHrP value in the high-normal range. Umbilical cord blood had considerably suppressed parathyroid hormone values but PTHrP levels that were indistinguishable from those in normal human plasma. Thus, PTHrP is present in high concentrations in breast milk but apparently does not gain access to the maternal circulation in significant amounts. In addition, women with pathologic hyperprolactinemia seem not to have increased levels of circulating PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effect of ageing on autonomic nervous system function.

We studied 76 healthy subjects (five-85 years) with a number of invasive and non-invasive tests of autonomic function. Age related effects were found with the tests of predominantly vagal cardiovascular function. However, there were no age related effects found with the tests of predominantly sympathetic cardiovascular function. The age of the subject should be taken into consideration when evaluating tests of autonomic function and each laboratory should establish its own control values.

Adolescent↗
PubMed1990

Comparison of algorithms of testing for use in automated evaluation of sensation.

Estimates of vibratory detection threshold may be used to detect, characterize, and follow the course of sensory abnormality in neurologic disease. The approach is especially useful in epidemiologic and controlled clinical trials. We studied which algorithm of testing and finding threshold should be used in automatic systems by comparing among algorithms and stimulus conditions for the index finger of healthy subjects and for the great toe of patients with mild neuropathy. Appearance thresholds obtained by linear ramps increasing at a rate less than 4.15 microns/sec provided accurate and repeatable thresholds compared with thresholds obtained by forced-choice testing. These rates would be acceptable if only sensitive sites were studied, but they were too slow for use in automatic testing of insensitive parts. Appearance thresholds obtained by fast linear rates (4.15 or 16.6 microns/sec) overestimated threshold, especially for sensitive parts. Use of the mean of appearance and disappearance thresholds, with the stimulus increasing exponentially at rates of 0.5 or 1.0 just noticeable difference (JND) units per second, and interspersion of null stimuli, Békésy with null stimuli, provided accurate, repeatable, and fast estimates of threshold for sensitive parts. Despite the good performance of Békésy testing, we prefer forced choice for evaluation of the sensation of patients with neuropathy.

Algorithms↗
PubMed1990

Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy.

The aims of this study were to examine in a prospective, randomized trial the efficacy of plasmapheresis in preventing irreversible renal failure in patients with multiple myeloma and to study the renal biopsy tissues from such patients. Twenty-one patients with active myeloma and progressive renal failure were randomized to one of two groups: group 1, forced diuresis and chemotherapy (10 patients), and group 2, forced diuresis, chemotherapy, and plasmapheresis (11 patients). Plasmapheresis and chemotherapy lowered the serum myeloma protein value much more rapidly than chemotherapy alone. Of 5 patients who were oliguric and undergoing dialysis at presentation, only 3 who were treated by plasmapheresis recovered. Of 16 polyuric patients, 5 in group 1 and 7 in group 2 showed improvement in renal function. The main factor that determined irreversibility of renal failure was the severity of myeloma cast formation.

Aged↗
PubMed1989

Clinicopathologic analysis of uterine malignant mixed müllerian tumors.

A clinicopathologic evaluation of 60 patients (median age, 66 years) presenting for primary treatment of uterine malignant mixed müllerian tumors between 1959 and 1982 was conducted. Surgical stage was utilized for assessment of survival by stage. With a minimum follow-up of 5 years, overall 2- and 5-year Kaplan-Meier survival estimates were 53 and 39%, respectively; they were 75 and 58% when disease was confined to the uterus and 27 and 15% when disease extended beyond the uterus. By log-rank and logit-rank analysis, surgical stage and depth of invasion stratified by stage were significant prognostic determinants; no significant association was found with carcinoma grade, sarcoma mitotic figure count, sarcoma histologic subtype, sarcoma necrosis, or capillary-like space involvement. No significant survival advantage was found for surgery plus irradiation or surgery plus chemotherapy compared with surgery alone after stratification according to stage. Progression-free survival after complete extirpation of macroscopic disease was not significantly different, stage for stage, between surgery alone and surgery plus radiotherapy.

Aged↗
PubMed1989

Nerve glucose, sorbitol, fructose, and myo-inositol at various time after feeding in streptozotocin-induced diabetes in rats.

Because fasting nerve myo-inositol (myo-Ins) is not decreased in patients with diabetes treated conventionally, in whom neuropathy may develop or may have already developed, it seems unlikely that myo-Ins is the metabolic abnormality that initiates diabetic neuropathy, if nerve myo-Ins is not spuriously high during fasting. At 6 weeks after induction of diabetes with streptozotocin in Sprague-Dawley rats we found that endoneurial glucose, sorbitol, and fructose were substantially increased and myo-Ins was decreased, as reported by others. By use of multiple linear regression to assess the effect of disease condition, time after feeding (1.5, 4, and 20 hours), and duration of diabetes (1,2,6 and 12 weeks) on nerve sugars and alcohol sugars, for nerve glucose, sorbitol, and fructose only disease condition was statistically significant factor. For nerve myo-Ins, disease group (control or diabetic rats) (P = 0.08), duration of diabetes (P = 0.02), time after feeding (P less than 0.001), duration x time (P = 0.01), group x duration (P = 0.03), and group x time (P = 0.05) were significant variables. Because nerve myo-Ins was lower at 20 hours than at 1.5 or 4 hours after feeding for all durations of diabetes, one can infer that in human nerve the lowest nerve myo-Ins, not high values, occur in the fasting state. Therefore, one would not expect to find lower nerve myo-Ins levels in human diabetics at times other than the fasting condition.

Animals↗