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Biomedical subjects

P C O'Brien

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

At least 325 records · Page 18Linked to original sources

Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol.

Fertility and outcome of pregnancy were examined in women participating in the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project. We compared 618 subjects who had prenatal exposure to DES with 618 control subjects. Fertility, measured in terms of pregnancies achieved, did not differ between the women exposed to DES and the controls. An increased risk of unfavorable outcome of pregnancy was associated with DES exposure (the relative risk of any unfavorable outcome of pregnancy was 1.69; P less than 0.001). Speculation on biologic mechanisms that might produce this difference is premature, since additional data about these subjects must be collected. Among DES-exposed women who became pregnant, 81 per cent had at least one full-term live birth.

Abnormalities, Drug-Induced↗

Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry.

Fascicles of the sural nerve from each of 20 diabetic patients, mostly with maturity-onset diabetes, were studied by biochemical and pathological techniques, and results were compared to values found in nerve specimens from 15 healthy persons. The sorbitol and fructose content was much more variable in diabetic than in healthy nerves. More than one-third of the diabetic nerves had sorbitol and fructose values above the highest levels for controls. myo-Inositol and scyllo-inositol content was not reduced in diabetic nerves. The sorbitol, fructose, and inositol concentrations could not be related to clinical, neurophysiological, or pathological severity of neuropathy. A comparison of scored symptoms and signs and clinical neurophysiological studies against morphometric and teased fiber studies of sural nerve demonstrated that the former three provide sensitive and reliable measures of severity of neuropathy that can be used for controlled clinical trials of diabetic neuropathy. The presence and type of teased fiber abnormalities could be related to the duration of diabetes and to symptoms of neuropathy. In untreated diabetics without symptoms of neuropathy, a higher than normal frequency of teased fibers showing segmental demyelination and remyelination was found. Untreated diabetics with symptomatic neuropathy showed two kinds of abnormalities: fibers with segmental demyelination and remyelination and fibers undergoing axonal degeneration. In treated diabetics, who often had longstanding neuropathy, the most common abnormalities were fibers undergoing axonal degeneration.

Diabetes Mellitus, Type 1↗

Incidence of skin cancers in patients with atopic dermatitis treated with coal tar. A 25-year follow-up study.

Coal tar ointments have been used for many years in the treatment of chronic eczematoid dermatitis. The possible carcinogenic effect of coal tar ointment and ultraviolet light (Goeckerman regimen), considered individually or in combination, has been of concern to physicians. A 25-year follow-up study was completed on 426 patients with atopic dermatitis and neurodermatitis who were hospitalized and treated with coal tar ointments and ultraviolet light at the Mayo Clinic from 1950 through 1954. These results were compared with those from a similar study that examined patients with psoriasis who also were treated with coal tar ointments and ultraviolet light. The results of this study suggest that the incidence of skin cancer is not significantly increased above the expected incidence for selected populations of the United States. This study offers reassurance about the relatively small risk of skin cancer developing in patients with atopic dermatitis and neurodermatitis treated with coal tar ointments and ultraviolet light (Goeckerman regimen).

Basal Cell Carcinoma↗

Imaging system for nerve and fiber tract morphometry: components, approaches, performance, and results.

This report describes the imaging system that was developed to recognize, count, size, and evaluate shapes of transverse myelinated fiber (MF) profiles in nerves and fiber tracts automatically and by operator interaction. Automatic analysis, without operator interaction, will either miss a variable percentage of small MFs (using thresholds that discriminate against all other tissue profiles) or include most MFs but spuriously detect other tissue profiles (using more sensitive thresholds). Systems such as this must therefore be operator-interactive. The system that was developed will, in a favorable histologic section, automatically detect and border myelin in more than 85% of MFs without inclusion of other tissue elements. The remainder of the MFs are then identified by the operator with the digitizer pen, and the myelin is automatically bordered or, in rare cases, drawn in. Very reliable, reproducible, and rapid measurements of MF number, size, and shape can be obtained with this system. From evaluation of the size and shape of MFs in semithin sections in the light microscope as compared with the same fibers in adjacent thin sections in the electron microscope, measurements by this system can be expressed as if they were obtained on thin sections. Evaluations can be analyzed statistically, with results printed out, displayed on a video screen, and graphed. Such a system will be useful in evaluating and following morphologic changes in number, size, and shape of MFs in development, aging, regeneration, neurotoxicity, and various diseases.

Computers↗

Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial fibre disarray and myocardial fibrosis.

The topography and specificity of fibre disarray and fibrosis in hypertrophic obstructive cardiomyopathy were determined in a histological study comprising 40 necropsy hearts--10 with hypertrophic cardiomyopathy, 10 with congestive cardiomyopathy, 10 with aortic valve stenosis, and 10 normal hearts. Seven standard regional sections were sampled from each heart and graded "double-blind" (tissue location and disease entity) for severity and extent of fibre dissarray and four distinct types of myocardial fibrosis. Statistical comparison of the severity and distribution of indices of fibre disarray and fibrosis within each group and between the normal and the disease groups showed that fibre disarray and fibrosis were qualitatively non-specific for hypertrophic cardiomyopathy. However, when fibre disarray was quantified (1) it was significantly increased in hypertrophic cardiomyopathy and allowed separation of hearts with hypertrophic cardiomyopathy from normal hearts and from those with congestive cardiomyopathy and aortic stenosis, (2) it did not vary significantly among sections of the left ventricle (that is, between the septum and the free wall) in hypertrophic cardiomyopathy, (3) it was closely associated with plexiform fibrosis, and (4) it varied independently of wall and septal thickness. Though the histogenesis of fibre disarray is unknown, it probably represents an exaggeration of a non-specific common pathway for many diverse pathophysiological processes.

Adolescent↗

The natural history of peripheral neuropathy in primary systemic amyloidosis.

The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.

Aged↗

Effect of chemotaxis on the interaction of cholera vibrios with intestinal mucosa.

Earlier reports from this laboratory have shown that chemotaxis is an important mechanism that expedites the in vitro association of cholera vibrios with intestinal slices and that affects the in vivo colonization and virulence of these bacteria to a significant degree. The data reported in the present communication indicate that there appears to be a chemotatic gradient attracting cholera vibrios not only to the surface of the mucus gel, but that this gradient continues for at least a considerable distance toward the base of the villi. It is shown further that a strain of Vibrio cholerae was attracted by all 20 amino acids tested, in contrast to Escherichia coli AW405 which is repelled by several of these. Finally, experiments are described that show that superior in vivo colonization of chemotatic vibrios (compared to nonchemotactic mutants) was correlated with a significantly higher degree of mucosal association. Such increased mucosal association of chemotatic vibrios has previously been shown only with mucosal slices in vitro.

Adhesiveness↗

Vaginal epithelial changes in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project.

Initial clinical findings are reported for the 3339 young women enrolled in the Diethylstilbestrol Adenosis (DESAD) project. Changes in the vaginal mucosa (VEC--vaginal epithelial changes), which were detected by colposcopy or iodine staining, occurred in 34% of 1275 participants identified by review of prenatal records 59% of participants who themselves requested entry into the project, and 65% of participants referred by a physician. Analysis of data on the 298 women who were identified by record review and whose prenatal records contained complete information about drug exposure indicated that VEC is most closely associated with the timing of the onset of intrauterine exposure to diethylstilbestrol (DES), total dose, and length of exposure. Frequency of VEC was also found to decrease with age. No instances of severe dysplasia, carcinoma in situ, invasive squamous cell adenocarcinoma, or clear cell carcinoma were observed among the women identified by record review.

Adenocarcinoma↗

A multiple testing procedure for clinical trials.

A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.

Clinical Trials as Topic↗

Introduction of automated systems to evaluate touch-pressure, vibration, and thermal cutaneous sensation in man.

Systems for automatic assessment of cutaneous touch-pressure, vibratory, and thermal sensation have been developed. These systems use stimuli which are quantified and reproducible, a two-alternative forced-choice technique, and programmed steps to test, score, and report. If normal responses from series of healthy persons have been measured, percentile values specific for test, site, age, and sex can be determined. Abnormality, as in neurological disease, can then be defined as the response which has a value greater than that of the 95th (or other) percentile. These systems may be used to detect and validate abnormalities of sensation in neurological disease and in persons at risk from new medications or from industrial toxins, and to monitor worsening or improvement of sensation in follow-up of a patient or in evaluation of therapeutic regimens.

Adult↗

Adhesion and chemotaxis as determinants of bacterial association with mucosal surfaces.

1) Chemotaxis of cholera vibrios facilitates the association of these bacteria with the mucosal surface. 2) Mucosal extracts can block the chemotactic receptors on the bacterial surface and thereby retard the association of chemotactic bacteria with the mucosal surface. 3) Chemotactic cholera vibrios grow more efficiently than non-chemotactic mutants in germfree mice and in isolated intestinal loops of rabbits. Conversely, non-chemotactic mutants grow more efficiently in infant mice. 4) Chemotaxis is therefore of considerable importance to the in vivo growth of cholera vibrios. The various mechanisms, including those of local immunity, by which bacterial chemotaxis can be exploited for the benefit of the host deserve further exploration.

Animals↗

Vectorcardiographic identification of myocardial scar: a discriminative study with automatically processed vectorcardiographic information.

A multivariate discriminative procedure for the vectorcardiographic identification of ischemic myocardial scarring was performed utilizing data from 1,162 vectorcardiograms (VCGs) obtained in clinically normal subjects and 90 VCGs obtained from patients proved at autopsy to have ischemic myocardial scars. The VCGs from patients with myocardial scars were divided into two groups, a design group of 50 cases and an evaluation group of 40 cases. The best vectorcardiographic variables to discriminate the clinically normal group from the design group with scars were identified by stepwise linear discrimination. Sixteen vectorcardiographic variables were then used for discriminative analysis. This analysis correctly identified myocardial scars in 45 of the 50 VCGs in the design group (sensitivity 90%); among the 1,162 VCGs from clinically normal subjects, 32 were misidentified as myocardial scar (specificity 97.2). The sensitivity of these defining criteria was then tested in the 40 cases of myocardial scar in the evaluation group and found to be reproducible; 34 of the 40 cases of this group (85.0%) were correctly identified as having a myocardial scar. The multivariate discriminative criteria developed in this study had greater sensitivity and specificity than standard methods usually employed in electrocardiography and vectorcardiography. The criteria defined need to be evaluated in a large series that includes instances of cardiac pathology of nonischemic nature.

Adolescent↗

A comparison of genital infections caused by chlamydia trachomatis and by neisseria gonorrhoeae.

Patients with culture-proven infections with Neisseria gonorrhoeae or Chlamydia trachomatis, or both, seen at the Olmsted County Health Department Sexually Transmitted Disease Clinic were evaluated for the presence of dysuria and exudate. Eighty-four patients (21%) had neither symptom. N. gonorrhoeae infection alone was most frequent (47%), but C. trachomatis predominated in men. Dysuria was most often detected in men infected with C. trachomatis, but exudate was most frequently found in men infected with N. gonorrhoeae alone or in mixed infections with C. trachomatis. The presence of both symptoms was more common in men than in women infected with N. gonorrhoeae or C. trachomatis. However, as the occurrence of dysuria and exudate was generally similar within the male and female groups, regardless of the organisms recovered, the type of infection cannot be accurately determined on the basis of symptomatology alone. The authors therefore believe that the diagnosis of genital infection by C. trachomatis or N. gonorrhoeae, or both, by culture technics is essential because effective treatment with antimicrobial therapy often requires this information.

Adolescent↗

Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project.

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted DES) during pregnancies occurring from the early 1940s to the mid-1960s. The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women. Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%). This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Adolescent↗

Effectiveness of intestinal phosphate binders in patients maintained by hemodialysis.

Two formulations of aluminum phosphate binders-aluminum hydroxide suspension and aluminum carbonate powder in the form of capsules-were found to be equally effective in lowering the plasma phosphate concentration. The effective dose was 4 g/day given in divided doses before meals and at bedtime. Side effects were negligible with this dosage for both preparations, but aluminum carbonate capsules were preferred by most patients because of the greater convenience of the capsule form. Coincident with the lowering of serum phosphorus concentrations, serum parathyroid hormone concentrations decreased approximately 30% from levels obtained while patients were taking placebo.

Administration, Oral↗