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Biomedical subjects

R Weinstein

Publications and source records attributed to R Weinstein.

At least 55 records · Page 3Linked to original sources

Cytogenetics of 158 patients with regional or disseminated melanoma. Subset analysis of near-diploid and simple karyotypes.

We report on the cytogenetic analyses of 158 cases of metastatic malignant melanoma, comprised of 63 cases with regional disease (RD) and 95 cases with distant (metastatic) disease (DD). Clonal structural abnormalities were identified in 126 (80%) cases and were significantly increased ( < 0.01 after adjusting for multiple comparisons) on chromosomes (in order of frequency of involvement) 1, 6, 7, 11, 9, and 3. Clustering of breakpoints occurred at 1p36, 1p22-q21, 6p11-q21, 9p, 11q23-qter, 13p (especially for cases with DD), and 19q13. The most common clonal numerical abnormalities, in a subset of 49 near-diploid cases were -10, -22, -9, +7, -19, and -Y. Analysis of chromosome segment gains and losses (CSRP) showed frequent loss of chromosomes 6 and 10, followed by equal rates of involvement of chromosomes 1, 7, and 9. Whole or segmental losses of chromosome 9 (especially 9p) correlate well with recent molecular genetic studies identifying putative suppressor genes, and are also likely important genetic abnormalities. However, based on the frequency of abnormalities in this large series of metastatic melanomas, it is likely that structural abnormalities of 1 and 6, and 10 are important in the pathogenesis of sporadic advanced melanoma.

Adult↗

Marital status and health among the elderly.

Many studies have documented a longevity advantage for married persons relative to their unmarried counterparts in all age groups. However, these studies have failed to determine whether the advantage experienced by married elderly persons arises mostly from selection and causal processes which operated at younger ages. This paper employs data from the Longitudinal Study of Aging (1984-1990) to explore whether marital status continues to exert any influence on health and mortality at the older ages. In the presence of an extensive set of controls for health status at the baseline survey, a series of logistic models are used to determine: (1) the magnitude of marital status effects on disability and on mortality, among older males and older females; and (2) the extent to which the social environment and economic status of the elderly can account for the existing disability and mortality differences by marital status.

Activities of Daily Living↗

Survival of lyophilized and reconstituted human red blood cells in vivo.

To assess the viability of human red blood cells that have been lyophilized and reconstituted to the hydrated state, we phlebotomized a unit of whole blood from six healthy male volunteers. Their packed red blood cells were lyophilized at -40 degrees C and stored at 4 degrees C. Upon rehydration, recovery of erythrocytes was 85.2 +/- 2.79%. Aliquots of 20 ml were labeled with 51Cr and re-infused into the original donors for red cell survival studies. The red cells retained ABO and Rh identity upon rehydration. There were no adverse clinical affects of re-infusion. The half time of 51Cr disappearance from the circulation was 31 +/- 8.19 days, and there was no evidence of significant splenic sequestration on the day of reinfusion. Red cell indices of the rehydrated erythrocytes were normal, oxyhemoglobin content was 98.58 +/- 1.46%, and P50 was 27.25 +/- 1.84 mmHg. Although deformability was slightly decreased, the osmotic fragility and filterability of the red cells were normal. These data demonstrate that human erythrocytes can be lyophilized and reconstituted to the hydrated state and survive normally in the circulation. Metabolic, osmotic, hematological and rheological function remains intact.

Adult↗

Simple numeric abnormalities as primary karyotype changes in ovarian carcinoma.

Simple near-diploid karyotypes in ovarian cancer may indicate either primary alterations related to tumor pathogenesis or abnormalities associated with early tumor progression. We have identified a series of 13 epithelial ovarian tumors with very simple karyotypes. Specifically, these karyotypes were near-diploid and displayed numeric abnormalities alone or combined with one or two structural alterations. The present series includes samples from 10 patients with newly diagnosed adenocarcinomas and 3 patients having borderline malignancies. Recurrent numeric abnormalities were identified and included 9/13 cases (69%) with +12, eight cases (62%) with +8, five cases (38%) with +7, three cases (23%) each with +3 or +5, and two cases (15%) with -X. Five cases in this series displayed certain numeric abnormalities (+12, +7, and -X) as the sole anomalies, thereby qualifying as primary karyotype changes. Of the 6 cases with structural abnormalities, 4 involved chromosome 19, 2 involved chromosome 1, and the remaining abnormalities or translocation partners involved other chromosomes. These findings indicate that some numeric abnormalities are primary karyotype alterations in patients with malignant epithelial ovarian tumors and that chromosome 19 may be preferrentially involved in structural rearrangements during early tumor progression.

Adult↗

Complications of therapeutic plasma exchange: a recent assessment.

The use of therapeutic plasma exchange, particularly for management of patients with neurological disorders, has steadily increased in our hospital since 1991, thus highlighting the need for continuing quality assurance of these services. We have reviewed the hemapheresis records of all 381 therapeutic plasma exchange procedures performed on a total of 63 patients from January 1991 through December 1992. Patients were referred for therapeutic plasma exchange for the following indications: acute Guillain-Barre syndrome, 31 patients (49.2%); chronic inflammatory demyelinating polyneuropathy, 15 patients (23.8%); myasthenia gravis, five patients (7.94%); paraproteinemic neuropathy, five patients (7.94%); thrombotic microangiopathies, six patients (9.52%) and Goodpasture syndrome, one patient (1.6%). Overall, 89% of patients were treated for neurological disorders. Complications of plasma exchange were noted during 17% (n = 65) of procedures involving 49% (n = 31) of patients treated. Approximately 91% of complications were classified as mild (55.4%) or moderately severe (35.4%) and did not prevent successful completion of the procedure. These were largely related to use of citrate-containing anticoagulants and additionally may have reflected the autonomic instability of many of the neuropathy patients. All four (6.15%) severe complications and one of two fatalities were related to the use of central venous access catheters. We conclude that therapeutic plasma exchange can be performed safely with acceptable toxicity caused by mild and moderately severe complications. Major complications may be minimized by careful management of central venous catheters when required for access.

Bacteremia↗

Clonal chromosome abnormalities in 54 cases of ovarian carcinoma.

As a prelude to assessing the relationship of chromosome alterations to clinical outcome in ovarian carcinoma, we report on the cytogenetic analysis on short-term cultures from 54 patients. All patients had histopathologically confirmed malignancy, with the majority of cases demonstrating serous ovarian adenocarcinomas. Structural alterations were evident in 52 cases, whereas numeric changes were identified in 13 cases. The most notable numeric abnormalities were loss of the X-chromosome (9/13 total cases) and +7 (3/9 diploid cases). Structural alterations most frequently involved chromosomes 1, 3, 6, 7, 11, and 12. Chromosomal breakpoints were shown to cluster in several chromosomal banding regions, including 1p36, 1p11-q21, 3p23-p10, 7p (especially 7p22), 11p, 11q, 12p13-q12, and 12q24. The frequency of structural alterations involving the following chromosome arms was found to be significantly increased: 1p (p < 0.01), 7p (p < 0.01), 11p (p < 0.01), 11q (p < 0.05), and 12p (p < 0.05). An analysis of the net gain or loss of chromosome segments was also performed, with the most consistent tendency observed being over-representation of 1q and chromosome 7, deletion of 1p, and loss of the X chromosome.

Adult↗

Advances in erythrocyte preservation and hemoglobin substitutes.

The desirability of extending the therapeutic benefits of erythrocyte transfusions beyond the currently available options is well established. Extended frozen storage of rare blood types, hemoglobin-based or artificial blood substitutes for treatment of short-term deficits in oxygen-carrying capacity, novel approaches to tissue oxygenation for cancer therapy, and efficient storage and availability of erythrocytes in military field installations are all potential applications of ongoing research and development efforts. This review explains the need for improvement in erythrocyte storage and development of blood substitutes, the current problems in the field, and the progress made toward solving these problems in the past year.

Animals↗

Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease.

Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were -17 and -19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes I (10/18-56%) and 6 (8/18-44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11-13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p.

Adenocarcinoma, Mucinous↗

Successful management of paraprotein-associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A.

Two patients with paraprotein-associated peripheral polyneuropathy were treated successfully using immunoadsorption of patient's plasma with staphylococcal protein A. Both had previously been treated with immunosuppressive agents or plasma exchange, and were rapidly relapsing at the time of their protein A immunoadsorption therapy. One patient was treated "on-line" with a blood cell separator, and one was treated "off-line." Both responded well to therapy with minimal toxicity. Serum levels of circulating immune complexes were elevated in one patient and remained so during and after therapy. Immunoadsorption with protein A should be investigated as a therapeutic option for patients with paraprotein-associated peripheral polyneuropathy. The therapy is relatively easy to administer, particularly "off-line," and was well tolerated by our patients. More experience, including formal clinical trials, will be required to properly define the indications for, and mechanism of response to, this therapy.

Aged↗

Inhibition of endothelium-dependent vasorelaxation by sickle erythrocytes.

Interactions between erythrocytes and vascular endothelium have been implicated in the pathogenesis of vaso-occlusion in sickle cell anemia. Sickle erythrocytes adhere to endothelial cells and facilitate trapping of rigid sickle cells in microvessels. Compensatory dilation of precapillary arterioles may mitigate the occlusion. The endothelium regulates vasoreactivity by elaborating endothelium-derived relaxing factor (EDRF), a small molecule that passes freely into vascular smooth muscle where it initiates vasorelaxation by activating soluble guanylate cyclase in the smooth muscle cell cytoplasm. Endothelial release of EDRF can be stimulated by agonists such as acetylcholine. It is highly sensitive to decomposition by superoxide anions and is rapidly bound and inactivated by oxyhemoglobin in solution. The purpose of this study was to determine whether sickle cell interaction with endothelium disrupts this mechanism of endothelial regulation of vasomotor tone. Transverse strips of rabbit aorta, mounted isometrically in organ baths, were contracted with norepinephrine, and relaxation responses to acetylcholine or other agonists were determined. Responses were measured under control conditions and again in the presence of oxyhemoglobin A or S, or erythrocytes or ghosts from normal control subjects or patients with homozygous sickle cell anemia. Sickle erythrocytes inhibited vasorelaxation to acetylcholine by 83%. Approximately half of the inhibition was attributable to a small amount of oxyhemoglobin S that was leaked into the buffer from the erythrocytes. Consistent with this, sickle erythrocyte ghosts inhibited vasorelaxation to acetylcholine by up to 45%. Ghosts from normal erythrocytes did not inhibit vasorelaxation to acetylcholine, and the inhibition seen with normal erythrocytes was entirely attributable to leakage of oxyhemoglobin A into the bath buffer.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Ritanserin, imipramine, and placebo in the treatment of dysthymic disorder.

Fifty outpatients with dysthymic disorder (DSM-III) were divided by double-blind randomized assignment into three groups given ritanserin, imipramine, and placebo, respectively. The trial was of 7 weeks' duration; by week 6, imipramine was clearly superior to placebo, whereas by week 7, both drugs caused significantly more improvement than the placebo. Although imipramine had slightly greater efficacy than ritanserin, it also had significantly more side effects. This was particularly evident in the higher dropout rate with imipramine. The efficacy and side effect profile of ritanserin makes it well tolerated and acceptable with dysthymic patients who, although they do not respond as quickly as patients with major depressive disorder, do show significant improvement, given sufficient time.

Adult↗

Three-dimensional reconstruction of human carotid arteries from images obtained during noninvasive B-mode ultrasound examination.

Previous investigators have demonstrated that B-mode ultrasonography can provide high resolution images of the carotid arteries. When combined with Doppler flow measurements, quantitative estimates of luminal narrowing may also be obtained. B-mode imaging is limited, however, in its ability to provide a composite view of the vessel wall, lumen and plaque. Spatial relations between structures visualized in individual frames must be inferred from repeated transducer passes over the designated site, or repeated review of recorded images, followed by a "mind's eye" reconstruction. Three-dimensional (3-D) reconstruction of serially recorded cross-sectional images from current B-mode systems represents a possible solution to this limited spatial display that preserves detail regarding vessel wall pathology. Accordingly, computer-based automated 3-D reconstruction was used to generate a tangible format with which to assess and compare serially and transcutaneously recorded 2-dimensional (2-D) B-mode images of the carotid arteries. One or more timed sweep recordings of the 2-D B-mode examination were obtained from 5 patients for 3-D reconstruction. In all cases, satisfactory 3-D reconstruction was accomplished in three 3-D formats: cylindrical, sagittal and lumen cast. Sagittal 3-D reconstruction provided information regarding pathologic alterations within the arterial wall. Experience with the cylindrical mode suggests that this 3-D format, particularly when the reconstructed vascular segment is hemisected, is optimally suited for those cases in which direct inspection of luminal topography is of special interest. The lumen cast display, used with a recently validated edge-detection algorithm, may enhance the use of B-mode ultrasound for assessment of luminal cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Electrophoretic analysis of low and high activity forms of catechol-O-methyltransferase in human erythrocytes.

Analysis of the catechol-O-methyltransferase (COMT) enzyme in human RBC lysates from 15 samples exhibiting inherited variations in level of activity and thermal stability was performed. Electrophoretic blotting and immune fixation was carried out following sodium dodecyl sulfate polyacrylamide gel electrophoresis or isoelectric focusing of lysate protein. These techniques did not reveal a major structural alteration of the protein that could account for the observed variation in enzyme activity or thermal stability. Future studies utilizing molecular genetic techniques should make it possible to determine the basis for inherited variations in human RBC COMT activity and thermal stability.

Catechol O-Methyltransferase↗

Efficacy of hormone replacement therapy in postmenopausal women with oral discomfort.

The increase in incidence of oral discomfort among women in a menopause is probably due to hormone modifications. This study evaluated the efficacy of hormone replacement therapy in 27 postmenopausal patients, aged 48 to 58 years, with oral discomfort and no local irritants and in 47 postmenopausal women with no oral discomfort. Patients were treated with conjugated estrogens for 21 days and medroxyprogesterone acetate from day 12 through day 21. Hormone-replacement therapy had no effect on oral cytology in the 40 symptom-free postmenopausal women compared with a group of 47 postmenopausal women who had no oral symptoms and were not treated. Hormone-replacement therapy relieved symptoms and improved oral cytohormonal features in 15 of 27 patients with symptoms. Nuclear estrogen receptors were found by immunohistochemical assay in 8 of 10 randomly selected patients with symptoms who responded to hormone-replacement therapy, but not in 2 patients who did not benefit from hormone-replacement therapy. Estrogen receptors were also found in 6 of 10 fertile women with no oral disease. Our results suggest that oral discomfort may be related to steroid hormone withdrawal only in some postmenopausal women and that replacement therapy may improve the clinical picture and cytologic features in this group of patients. Immunohistochemical identification of estrogen receptors may help to identify patients for whom hormone-replacement therapy may be beneficial.

Burning Mouth Syndrome↗

The implementation of a restrictive worksite smoking policy in a large decentralized organization.

This study investigates the implementation of a restrictive smoking policy in decentralized worksites. A model which includes four elements--concept, context, process, and outcomes--is used as a framework for identifying characteristics that influence implementation. The organization studied was a state human services agency with approximately 400 worksites spread across 12 geographic regions. Quantitative data collection included three cross-sectional surveys of employees and supervisors administered before and after the date the policy became effective. Qualitative data were collected from three sources, including written comments on surveys, focus groups, and structured interviews with supervisors and top administrators. Tabular analyses and one-way analyses of variance were used to analyze quantitative data. Qualitative data were examined for key themes and have been used to elucidate findings. Those characteristics related to concept, context, and process which appeared to have the strongest influence on expected and unexpected outcomes of the restrictive smoking policy were degree of policy restrictiveness, job characteristics, perceived level of participation in formulation and implementation, and support of supervisors responsible for day to day enforcement. In particular, in this decentralized organization, lack of participation was found to underlie many of the problems experienced in implementation. The practical implications for developing and implementing a worksite restrictive smoking policy are discussed.

Cross-Sectional Studies↗

[An update on nonsurgical periodontal therapy. A review of the literature].

In this review the authors examine the currently accepted nonsurgical treatment modalities, the role of pharmacotherapeutics in the prevention and treatment of periodontal disease and in the maintenance of the results. They also consider the utility of nonsurgical treatment for cases of advanced periodontal disease and the future direction of clinical practice and research.

Anti-Bacterial Agents↗