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Biomedical subjects

R Weinstein

Publications and source records attributed to R Weinstein.

At least 37 records · Page 2Linked to original sources

Treatment of high-risk, refractory acquired methemoglobinemia with automated red blood cell exchange.

Ingestion of strong oxidant substances may result in acquired methemoglobinemia, a clinical condition in which the oxidized blood hemoglobin is incapable of delivering oxygen to the tissues, and the patient becomes cyanotic. Traditional first-line therapy consists of infusion of methylene blue, whose action depends on the availability of reduced nicotinamide adenine nucleotide phosphate (NADPH) within the red blood cell (RBC). Some patients, particularly those who are deficient in glucose-6-phosphate dehydrogenase (G6PD), will not benefit from methylene blue. In these patients, and in some patients who have ingested very strong oxidants, methylene blue may also precipitate Heinz body hemolytic anemia. We present a case of severe, acquired methemoglobinemia in a 26-month-old, 9.8-kg boy with G6PD deficiency. He was cyanotic, in respiratory failure, intubated in a pediatric intensive care unit. In typical fashion, he did not respond to methylene blue. Manual exchange of two whole blood volumes, performed over 4 1/2 hr, also failed to resolve his severe methemoglobinemia. An automated RBC exchange (1.3 RBC volume), lowered his methemoglobin content from 31.8% to 7% in a single 40-min procedure. Thereafter his methemoglobin level continued to decrease rapidly and spontaneously. He was discharged home 2 days later, with 0.4% methemoglobin. To our knowledge, this is the first report to demonstrate the (potentially superior) effectiveness of automated RBC exchange for treatment of patients with high-risk acquired methemoglobinemia, that is, those with G6PD deficiency or who have ingested strong oxidants.

Automation↗

Metachronous renal cell carcinoma metastasis to the contralateral adrenal gland.

OBJECTIVES: Metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland is very rare. We review our experience with 5 such patients and compare it with reports in the literature. METHODS: The records of all 350 patients who underwent nephrectomy for renal cell carcinoma in our center between 1975 and 1992 were reviewed. Five patients were found to have had solitary metachronous metastases to the contralateral adrenal gland on follow-up. RESULTS: The adrenal metastasis was discovered 18 to 210 months (mean 66.8) after nephrectomy. In 2 patients the lesion was found incidentally on routine computed tomography scan; in the other 3 patients, diagnosis was by ultrasonography, performed because of flank pain and weight loss or routine follow-up. All patients underwent adrenalectomy. Survival ranged from 8 to 64 months (mean 36.4); 3 patients had no evidence of disease at 42, 44, and 64 months postoperatively, and 2 patients died of pulmonary metastasis at 8 and 24 months. Analysis of the clinical data of our 5 patients together with the 9 we found in the published reports revealed that the mean interval between nephrectomy and the appearance of adrenal metastasis was shorter in the patients who died. CONCLUSIONS: The results of adrenalectomy for metachronous metastasis of renal cell carcinoma to the contralateral adrenal gland are unpredictable. The prognosis is somewhat better when the mean interval between the nephrectomy and the appearance of the adrenal metastasis is longer than 18 months. We recommend adrenalectomy because long-term survival is expected in some of these patients.

Adrenal Gland Neoplasms↗

Fluid dynamics of gingival tissues.

Gingival hydraulic interstitial pressure was measured with glass micropipettes in 18 anesthetized rabbits at the level of the free gingiva, attached gingiva and oral mucosa facing the incisors and molar teeth. Samples of gingival interstitial tissue fluid were also collected by inserting nylon wicks in the subepithelial layer of the oral mucosa. Colloid osmotic pressure of interstitial fluid samples was measured with an osmometer whose membrane had a molecular cutoff of 30 kD. Hydraulic interstitial pressure from the free gingiva, at an average distance of 300 microns from sulcular space, was -1.3 +/- 0.9 (SD) cmH2O. Mean colloid osmotic pressure of gingival tissues interstitial fluid was 13.1 cmH2O, corresponding to a protein concentration of 2.8 g/dl. The thickness of the sulcular epithelium and of the oral gingival epithelium (data from 2 rabbits) were approximately 100 microns; the minimal distance of microvessels from the surface of the sulcular epithelium was approximately 150 microns. Based on hydraulic and colloid osmotic data, the Starling balance of pressures causes fluid filtration from gingival capillaries to gingival interstitium; however, across the sulcular epithelium, the pressure gradient sustains fluid absorption from the sulcus into the gingival interstitium. Plasma proteins may leak from microvessels into gingival interstitium, down convective bulk flow and via a concentration dependent diffusive component. At sulcular level, proteins may leak into the sulcus down a concentration gradient. Thus, at sulcular level a peculiar condition occurs in that there is an absorption gradient for water but a filtration gradient for plasma proteins.

Absorption↗

Biologic and therapeutic determinants of bone mineral density in multiple myeloma.

The net impact of malignancy and anti-tumor therapy on bone resorption in myeloma is poorly understood because conventional skeletal radiographs are relatively insensitive for the diagnosis and monitoring of bone disease. We performed determinations of bone mineral density (BMD) at the lumbar spine, femoral neck and radial diaphysis by dual energy X ray absorptiometry (DEXA) in 168 consecutive patients with myeloma seen at our institution. Follow up studies were performed in 41 of these patients. A detailed analysis of patient and disease characteristics was performed to identify the determinants of BMD. Compared to normal age and sex matched controls, mean (+/- SE) BMD was significantly decreased at the lumbar spine (Z score -0.4 +/- 0.10) and femoral neck (Z score -1.0 +/- 0.10), but was surprisingly above normal at the radial diaphysis (Z score +0.35 +/- 0.10), a cortical bone site devoid of hematopoietic marrow, suggesting a differential bone preserving effect at this site. Lack of correlation between the BMD findings and the presence or extent of radiographically evident osteolytic lesions suggested the presence of a systemic bone disease. On multivariate analysis, duration of disease >12 months (p = 0.003) and female sex (p = 0.01) were independently associated with a lower BMD at the femoral neck/lumbar spine. On follow up DEXA (n = 41), BMD increased at > or = 1 site in 9 of 20 patients receiving bisphosphonates and in only 2 of 21 patients not receiving such therapy (p = 0.02). Similarly a decline in BMD at > or = 1 site was seen in 9 of 21 patients not receiving bisphosphonates, irrespective of the disease response status. Interval pamidronate therapy (p = 0.0007) and a low serum beta-2-microglobulin (< 2.5 mg/l) (p = 0.04) were the two most significant variables associated with an increase in BMD on multivariate analysis. These data suggest that myeloma is associated with a systemic bone disease with progressive generalized cancellous bone loss and a bone preserving effect on the radial cortical bone. The early use of bisphosphonates may improve myeloma related bone disease.

Absorptiometry, Photon↗

Thrombotic thrombocytopenic purpura following coronary artery bypass graft surgery: prospective observations of an emerging syndrome.

Thrombotic thrombocytopenic purpura (TTP) is a rapidly progressive syndrome of thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. While most TTP is idiopathic, we have observed four cases following coronary artery bypass graft (CABG) surgery in a 2-year period. We have studied these cases prospectively to define the natural history, and potentially unique characteristics, of a post-CABG TTP syndrome. On average, the onset occurred 4.75 days postoperatively (post-op), but the diagnosis was made 8.5 days post-op. All four patients exhibited microangiopathic hemolysis, thrombocytopenia, mental status changes, and severe renal failure. Three also had unexplained fever. All patients received therapeutic plasma exchange for 5, 6, 8, and 11 days, respectively, and all achieved complete hematological remission. Three patients required dialysis for 7, 15, and 16 days, respectively, but were restored to baseline renal function if they survived. One patient with severe pre-existing peripheral vascular disease died of Candida sepsis. None of the surviving patients have relapsed at a median follow-up of 19 months. These cases appear distinguished by a delay in diagnosis despite intensive medical supervision, a florid presentation with most, or all, of the components of the classic TTP pentad, an excellent and rapid response to plasma exchange, and a tendency not to relapse. As such, they may represent a subgroup characterized by a more rapid and severe onset, but also a rapid response to therapy and earlier recovery than the typical idiopathic form of TTP. An aggressive approach to management is warranted.

Aged↗

Evaluation of radiologist performance using telemedicine services.

Observer performance of radiologists using a telemedicine service was evaluated. Diagnoses between the rural and consulting radiologists agreed 84% of the time. The main reason for disagreement was extent of lesion rather than type or absence/presence. Consulting times and image quality were considered adequate.

Clinical Competence↗

Bartholin's gland hyperplasia in a postmenopausal woman.

BACKGROUND: Benign solid tumors of Bartholin's gland are rare, with only six cases reported in the English language literature since 1966. Bartholin's gland hyperplasia has not been described. CASE: A postmenopausal woman with painless bilateral vulvar masses underwent surgical removal of one of the masses, which revealed a well-circumscribed, nonencapsulated tumor composed of mucous glands and ducts within a dense fibrous stroma, most consistent with hyperplasia of Bartholin's gland. CONCLUSION: Hyperplasia represents a new etiology for the enlarged Bartholin's gland. Whether the hyperplastic gland forms in response to a stimulus is unclear. However, it appears to share some features with Bartholin's gland hamartoma or adenoma.

Bartholin's Glands↗

Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations.

Multidrug resistance (MDR), especially that associated with overexpression of MDR1 and its product, P-glycoprotein (Pgp), is thought to play a role in the outcome of therapy for some human tumors; however, a consensus conclusion has been difficult to reach, owing to the variable results published by different laboratories. Many factors appear to influence the detection of Pgp in clinical specimens, including its low and heterogeneous expression; conflicting definitions of detection end points; differences in methods of sample preparation, fixation, and analysis; use of immunological reagents with variable Pgp specificity and avidity and with different recognition epitopes; use of secondary reagents and chromogens; and differences in clinical end points. Also, mechanisms other than Pgp overexpression may contribute to clinical MDR. The combined effect of these factors is clearly important, especially among tumors with low expression of Pgp. Thus, a workshop was organized in Memphis, Tennessee, to promote the standardization of approaches to MDR1 and Pgp detection in clinical specimens. The 15 North American and European institutions that agreed to participate conducted three preworkshop trials with well-characterized MDR myeloma and carcinoma cell lines that expressed increasing amounts of Pgp. The intent was to establish standard materials and methods for a fourth trial, assays of Pgp and MDR1 in clinical specimens. The general conclusions emerging from these efforts led to a number of recommendations for future studies: (a) although detection of Pgp and MDR1 is at present likely to be more reliable in leukemias and lymphomas than in solid tumors, accurate measurement of low levels of Pgp expression under most conditions remains an elusive goal; (b) tissue-specific controls, antibody controls, and standardized MDR cell lines are essential for calibrating any detection method and for subsequent analyses of clinical samples; (c) use of two or more vendor-standardized anti-Pgp antibody reagents that recognize different epitopes improves the reliability of immunological detection of Pgp; (d) sample fixation and antigen preservation must be carefully controlled; (e) multiparameter analysis is useful in clinical assays of MDR1/Pgp expression; (f) immunostaining data are best reported as staining intensity and the percentage of positive cells; and (g) arbitrary minimal cutoff points for analysis compromise the reliability of conclusions. The recommendations made by workshop participants should enhance the quality of research on the role of Pgp in clinical MDR development and provide a paradigm for investigations of other drug resistance-associated proteins.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prevention of citrate reactions during therapeutic plasma exchange by constant infusion of calcium gluconate with the return fluid.

We have examined the effectiveness of intravenous calcium gluconate infusion in the prevention of citrate reactions during therapeutic plasma exchange. Over 3 years, 636 procedures were performed on 90 patients, mostly for treatment of neurological disorders. Return fluid consisted of 4-5% human serum albumin in 0.9% NaCl. Anticoagulant ACD-A was used at a starting ratio of 1:16. Whole blood flow rates were 70-80 ml/min. Treatments were divided into three groups for management of citrate reactions: Group A (360 treatments) were managed using simple measures only, including slowing the whole blood flow rate, altering the ACD:whole blood flow ratio, and oral calcium carbonate wafers; Group B (102 treatments) received small intravenous boluses of 10% calcium gluconate, us to 25 ml during the procedure; Group C (174 treatments) received constant infusion of calcium gluconate (10 ml/liter of return fluid) during the procedure. Citrate reactions occurred in 35.6% of Group A and 29.4% of Group B treatments (P = 0.3), but in only 8.6% of Group C treatments (P < 0.0001). Men with and without reactions were the same age (mean 63.3 vs. 61 years, P = 0.0823), but women with reactions were younger than women without reactions (mean 49.9 vs. 57.9 years, P < 0.0001). Supplementation of the return fluid with calcium gluconate is an effective, convenient, and well-tolerated method for prevention of citrate toxicity during therapeutic plasma exchange procedures using albumin-based return fluid.

Adolescent↗

Amplification of 19q13.1-q13.2 sequences in ovarian cancer. G-band, FISH, and molecular studies.

In this study of ovarian carcinoma, we extended previous findings by performing FISH using chromosome 19 paint and microFISH probes and patient samples with and without abnormalities of chromosome 19 identified by G-banding. Karyotype interpretations of der(19) were confirmed, while additional 19 translocations were also detected by FISH with 19WCP in some cases. Similar FISH studies of ovarian carcinoma cell lines found chromosome 19 abnormalities even after extensive in vitro culture. MicroFISH probes were generated by chromosome microdissection from two cases with hsr(19) and mapped to 19q13.2 and 19q13.1-.2, respectively. FISH with these microFISH probes alone or in combination with a 19WCP probe to four patient samples and seven cell lines showed that 65% of chromosome 19 structural abnormalities contained 19q13.1-q13.2 sequences, sometimes as large hsrs. Ovarian cancer cell lines showed amplification and overexpression of the AKT2 putative oncogene, but not the ERCC-2 DNA repair gene in this chromosomal region. In addition to AKT2, amplification and overexpression of other yet-unidentified genes in the 19q13.1-q13.2 region may contribute to ovarian carcinoma pathogenesis or progression.

Chromosome Aberrations↗

Psychological intervention in patients with poor compliance.

In this article, the authors examine the compliance of periodontal patients from a behavioral psychology perspective. The causes of non-compliance are analyzed along with the main methods of intervention. An experiment was carried out in which various behaviour modification techniques were compared. This study, in particular, examined the effect of periodontist's use of behaviour modification techniques on patient compliance in four treatment maintenance conditions. A functional analysis of compliance and non-compliance behaviour revealed various treatment opportunities. Hence, 4 treatment conditions (which included basic oral hygiene instructions, performance feedback, behavioural self-management, and positive reinforcement) were compared in 3 phases. Data collected over a period of 3 months indicated that behavioural self-management plus positive reinforcement increase patient compliance significantly. Implications for further research are discussed in terms of analyzing the cost of each component procedure for both the patient and the doctor in terms of time, money and effort required. Hence, the present study demonstrates that behavioural strategies can make a significant contribution to the area of patient management.

Adult↗

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↗