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S Goldfarb

Publications and source records attributed to S Goldfarb.

At least 19 recordsLinked to original sources
PubMed2001

Complications and patient satisfaction following expander/implant breast reconstruction with and without radiotherapy.

PURPOSE: To compare the rates of complications and patient satisfaction among breast cancer patients treated with mastectomy and tissue expander/implant reconstruction with and without radiotherapy. METHODS AND MATERIALS: As part of the Michigan Breast Reconstruction Outcome Study (MBROS), breast cancer patients undergoing mastectomy with reconstruction were prospectively evaluated with respect to complications, general patient satisfaction with reconstruction, and esthetic satisfaction. Included in this study was a cohort of women who underwent breast reconstruction using an expander/implant (E/I). A subset of these patients also received radiotherapy (RT). At 1 and 2 years postoperatively, a survey was administered which included 7 items assessing both general satisfaction with their reconstruction and esthetic satisfaction. Complication data were also obtained at the same time points using hospital chart review. Radiotherapy patients identified in the University of Michigan Radiation Oncology database that underwent expander/implant reconstruction but not enrolled in the MBROS study were also added to the analysis. RESULTS: Eighty-one patients underwent mastectomy and E/I reconstruction. Nineteen patients received RT and 62 underwent reconstruction without RT. The median dose delivered to the reconstructed breast/chest wall, including boost, was 60.4 Gy (range, 50.0-66.0 Gy) in 1.8- to 2.0-Gy fractions. With a median follow-up of 31 months from the date of surgery, complications occurred in 68% (13/19) of the RT patients compared to 31% (19/62) in the no RT group (p = 0.006). Twelve of 81 patients (15%) had a breast reconstruction failure. Reconstruction failure was significantly associated with experiencing a complication (p = 0.0001) and the use of radiotherapy (p = 0.005). The observed reconstruction failure rates were 37% (7/19) and 8% (5/62) for patients treated with and without radiotherapy, respectively. Tamoxifen was associated with a borderline risk of complications (p = 0.07) and a significant risk of reconstruction failure (p = 0.01). Sixty-six patients of the study group completed the satisfaction survey; 15 patients did not. To offset potential bias for patients not completing the survey, we analyzed satisfaction data assuming "dissatisfaction" scores for surveys not completed. In the analysis of patients with unilateral E/I placement, reconstruction failure was significantly associated with a lower general satisfaction (p = 0.03). Ten percent of patients experiencing a reconstruction failure were generally satisfied compared to 23% who completed E/I reconstruction. In addition, tamoxifen use was associated with a significantly decreased esthetic satisfaction (p = 0.03). Radiotherapy was not associated with significantly decreased general or esthetic satisfaction. CONCLUSION: Irradiated patients had a higher rate of expander/implant reconstruction failure and complications than nonirradiated patients. Despite these differences, our pilot data suggest that both general satisfaction and patient esthetic satisfaction were not significantly different following radiotherapy compared to patients who did not receive RT. Although statistical power was limited in the present study and larger patient numbers are needed to validate these results, this study suggests comparable patient assessment of cosmetic outcome with or without radiotherapy in women who successfully complete expander/implant reconstruction.

Adult↗
PubMed2001

TGF-beta: a crucial component of the pathogenesis of diabetic nephropathy.

In summary, metabolic, hemodynamic, and genetic factors are all important in the development and progression of diabetic nephropathy (33). Recent studies using cell culture techniques and experimental animal models have provided important insight into the role of hyperglycemia in this disease. The nature of the factors directly arising as a consequence of hyperglycemia and the steps involved in diabetic complications are not completely understood. The characteristic lesions of diabetic nephropathy may be intimately related to the effects of high ambient glucose on intracellular signaling events, various growth factors/cytokines, and nonenzymatic glycation of proteins (36). The growth factor TGF-beta has emerged as a key participant in the cascade of events which leads to kidney sclerosis. Increased TGF-beta expression in the kidney in diabetes mellitus mediates the renal actions of high ambient glucose to promote cellular hypertrophy and stimulate extracellular matrix biosynthesis. Neutralizing the actions of TGF-beta with highly specific monoclonal antibodies or with application of antisense technology can effectively prevent the induction of the kidney lesions of diabetes in mice independent of any changes in blood glucose levels. Such maneuvers are crucial for establishing proof-of-concept and Koch's postulates (17), but they are still far removed from clinical applicability. Nevertheless, it is hoped that further studies to elucidate the efficacy of novel interventions to intercept the activity of the renal TGF-beta system will prove useful for effectively halting the progression of diabetic nephropathy.

Animals↗
PubMed2000

FRAP DNA-dependent protein kinase mediates a late signal transduced from ultraviolet-induced DNA damage.

Ultraviolet radiation induces signal transduction at both early (<6 h) and late (>6 h) times after exposure. The inflammatory and immunosuppressive cytokine tumor necrosis factor alpha is induced at late times, and is induced by ultraviolet-induced DNA damage, as defects in DNA repair increase, and enhanced photoproduct repair reduces, tumor necrosis factor alpha expression. Here we show that late tumor necrosis factor alpha gene expression is sensitive to rapamycin, implicating FKBP12-rapamycin-associated protein, a member of the DNA protein kinase family, as a signal transducer of ultraviolet-induced DNA damage. FKBP12-rapamycin-associated protein was localized in the nucleus of keratinocytes and its level was increased following ultraviolet irradiation. Immuno- precipitated FKBP12-rapamycin-associated protein was stimulated by ultraviolet-irradiated DNA to phosphorylate p53 in vitro, and in vivo rapamycin reduced ultraviolet induction of p53 by 20%. Rapamycin further inhibited the ultraviolet-induced phosphorylation of the FKBP12-rapamycin-associated protein downstream target kinase p70S6K. In mice, topical application of rapamycin before ultraviolet exposure protected against suppression of the contact hypersensitivity that is a hallmark of ultraviolet-induced cytokine gene expression. These results demonstrate that the FKBP12-rapamycin-associated DNA protein kinase transduces the signal of ultraviolet-induced DNA damage into production of immunosuppressive cytokines at late times after ultraviolet irradiation.

DNA↗
PubMed2000

The urine/plasma electrolyte ratio: a predictive guide to water restriction.

Patients with hypotonic hyponatremia are encountered commonly in the general practice of medicine. Nearly all strategies for the management of subacute or chronic hyponatremia call for some amount of water restriction. The considerations for such a prescription have not been addressed in the literature. We describe therefore a simple approach grounded in the physiology of electrolyte-free water clearance that can be used at the bedside.

Electrolytes↗
PubMed2000

Prospective analysis of psychosocial outcomes in breast reconstruction: one-year postoperative results from the Michigan Breast Reconstruction Outcome Study.

In the past decade, changing attitudes toward breast reconstruction among both patients and providers have led a growing number of women to seek breast reconstruction after mastectomy. Although investigators have documented the psychological, social, emotional, and functional benefits of breast reconstruction, little research has evaluated the effects of procedure choice on these outcomes. The current study prospectively evaluated and compared psychosocial outcomes for three common options for mastectomy reconstruction: tissue expander/implant, pedicle TRAM, and free TRAM techniques. In a prospective cohort design, patients undergoing postmastectomy reconstruction for the first time with expander/implant, pedicle TRAM, or free TRAM procedures were recruited from 12 centers and 23 plastic surgeons in the United States and Canada. Before reconstruction and at 1 year after reconstruction, patients were evaluated by a battery of questionnaires consisting of both generic and condition-specific surveys. Outcomes assessed included emotional well-being, vitality, general mental health, social functioning, functional well-being, social well-being, and body image. Baseline (preoperative) scores and the change in scores (the difference between postoperative and preoperative scores) were compared across procedure types using t tests and analysis of covariance. Preoperative and 1-year postoperative surveys were obtained from 273 patients. Procedure type was reported in 250 patients, of whom 56 received implant reconstructions, 128 pedicle TRAM flaps, and 66 free TRAM flaps. A total of 161 immediate and 89 delayed reconstructions were performed. Among women receiving immediate reconstruction, significant improvements were observed in all psychosocial variables except body image. However, no significant effects of procedure type on these changes over time existed. Similarly, delayed reconstruction patients had significant increases in emotional well-being, vitality, general mental health, functional well-being, and body image. Although the choice of reconstructive technique did not significantly impact most of these outcomes, significant differences existed among procedure types for three psychosocial subscales. Patients undergoing delayed expander/implant reconstructions reported greater improvements in vitality and social well-being relative to women receiving delayed TRAM procedures. By contrast, delayed TRAM patients noted significantly greater gains in body image compared with women choosing delayed expander-implant reconstruction. The authors conclude that both immediate and delayed breast reconstructions provide substantial psychosocial benefits for mastectomy patients. Although the choice of reconstructive procedure does not seem to significantly affect improvements in psychosocial status with immediate reconstruction, our data suggest that procedure type does have a significant effect on gains in vitality and body image for women undergoing delayed reconstruction.

Adaptation, Psychological↗
PubMed1999

The utility of decision support, clinical guidelines, and financial incentives as tools to achieve improved clinical performance.

BACKGROUND: Whether one seeks to reduce inappropriate utilization of resources, improve diagnostic accuracy, increase utilization of effective therapies, or reduce the incidence of complications, the key to change is physician involvement in change. Unfortunately, a simple approach to the problem of inducing change in physician behavior is not available. COMPREHENSIVE CLINICAL GUIDELINES: There is a generally accepted view that expert, best-practice guidelines will improve clinical performance. However, there may be a bias to report positive results and a lack of careful analysis of guideline usage in routine practice in a "postmarketing" study akin to that seen in the pharmaceutical industry. FINANCIAL INCENTIVES: Systems that allow the reliable assessment of quality of outcomes, efficiency of resource utilization, and accurate assessment of the risks associated with the care of given patient populations must be widely available before deciding whether an incentive-based system for providing the full range of medical care is feasible. DECISION SUPPORT: Decision support focuses on providing information, ideally at the "point of service" and in the context of a particular clinical situation. Rules are self-imposed by physicians and are therefore much more likely to be adopted. CONCLUSION: As health care becomes corporatized, with increasing numbers of physicians employed by large organizations with the capacity to provide detailed information on the nature and quality of clinical care, it is possible that properly constructed guidelines, appropriate financial incentives, and robust forms of decision support will lead to a physician-led, process improvement approach to more rational and affordable health care.

Benchmarking↗
PubMed1998

Quantitative studies of human urinary excretion of uropontin.

Uropontin is the urinary form of osteopontin, an aspartic acid-rich phosphorylated glycoprotein. Uropontin has been previously shown to be a potent inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals and the binding of these crystals to renal epithelial cells. Quantitative data defining the excretion of this protein are necessary to determine its role in urinary stone formation. In the present studies, we determined uropontin excretion rates of normal humans. Urine samples were obtained under conditions of known dietary intake from young adult human volunteers with no history, radiographic or laboratory evidence of renal disease. Urinary concentrations of uropontin were measured by a sensitive ELISA employing an affinity purified polyclonal antiserum to uropontin. Thirteen normal subjects ingested a constant diet providing 1 gram of calcium, 1 gram of phosphorus, 150 mEq of sodium and 1 gram of protein per kilogram of body wt per day during an eight day study period. The relationship of urinary volume to uropontin excretion was assessed by varying fluid intake on the last four days of the study to change the mean urine volume/24 hr by > 500 ml. Urine collected in six hour aliquots for eight days was analyzed for uropontin by ELISA, and for calcium, and creatinine. Daily uropontin excretion of 13 individual subjects was 3805 +/- 1805 micrograms/24 hr (mean +/- 1 SD). The mean urinary levels (1.9 micrograms/ml) detected in the present study are sufficient for inhibition of crystallization; our previous studies have demonstrated that the nucleation, growth and aggregation of calcium oxalate crystals and their binding to renal cells in vitro are inhibited by this concentration of purified uropontin. In contrast to the regular pattern of diurnal variation of calcium excretion seen in most subjects, uropontin excretion showed no regularity of diurnal variation and was not directly related to either calcium or creatinine excretion or changes in urinary volume. However, uropontin concentration varied inversely with urine volume (P < or = 0.001), so that the highest uropontin concentrations occurred when urine volume was the lowest. We conclude that the physiologic characteristic of an inverse relationship of uropontin concentration to urine volume favors protection from urinary crystallization of calcium oxalate by uropontin. Our quantitative definition of urinary uropontin excretion of normal adults provides the basis for the evaluation of uropontin excretion by individuals who have formed urinary stones.

Adult↗
PubMed1998

Predictive performance of ten equations for estimating creatinine clearance in cardiac patients. Iohexol Cooperative Study Group.

OBJECTIVE: The predictive performance of 10 equations used to estimate creatinine clearance (Clcr) was assessed retrospectively from data collected on 420 patients. DESIGN: This study is a retrospective data analysis of information collected on hemodynamically stable patients awaiting coronary angiography during the Iohexol Cooperative Study. SETTING: The Iohexol Cooperative Study was a multicenter study that compared nephrotoxicity of high- and low-osmolar contrast media in patients undergoing coronary angiography. Data used for this analysis were preangiography 24-hour urine collections that were primarily collected in hospitalized patients. PATIENTS: Patients selected from the Iohexol Cooperative Study database for analysis were participants categorized into one or more of six subgroups: elderly (n = 222), hypoalbuminemic (n = 25), chronic renal insufficiency (n = 128), low serum creatinine (n = 115), obese (n = 208), and diabetic (n = 191) who had baseline urine collections of at least 24 hours. OUTCOME MEASURES: Predictive performance was assessed using bias, precision, slopes, and y-intercepts. RESULTS: The Salazar-Corcoran equation was unbiased in the entire group as well as in five of the subgroups. The Cockcroft-Gault equation was unbiased in three of the subgroups. All other equations were biased in predicting Clcr in the entire group as well as in at least four of the subgroups. Precision was generally poor. All slopes were significantly different than one and all y-intercepts were significantly different than zero (p < 0.01). Correlation coefficients were between 0.63 and 0.79 with the exceptions of the low serum creatinine subgroup (r values 0.35-0.64) and the Davis-Chandler equation (r values 0.35-0.71 across groups). CONCLUSIONS: Of the equations studied, Salazar-Corcoran and Cockcroft-Gault appear to be the best for predicting Clcr.

Aged↗
PubMed1997

Language guiding therapy: the case of dehydration versus volume depletion.

Indiscriminate use of the terms dehydration and volume depletion, so carefully crafted by our predecessors, risks confusion and therapeutic errors. These two conditions should be distinguished at the bedside and in how we speak to one another. Dehydration largely refers to intracellular water deficits stemming from hypertonicity and a disturbance in water metabolism. The diagnosis of dehydration cannot be established without laboratory analysis of p[Na +] or calculation of serum tonicity. In contrast, volume depletion describes the net loss of total body sodium and a reduction in intravascular volume and is best termed extracellular fluid volume depletion. The diagnosis of this condition relies principally on history, careful physical examination, and adjunctive data from laboratory studies. The pathophysiology of both dehydration and extracellular fluid volume depletion must be understood if these conditions are to be recognized and appropriately treated when they occur separately or together. There is no inclusive therapy for all situations. For example, indiscriminate treatment with 0.45% saline cannot be recommended when these conditions coexist because extracellular fluid volume depletion is often treated rapidly with 0.9% saline and dehydration is often treated more slowly with 5% dextrose.

Dehydration↗
PubMed1997

CT depiction of experimental liver tumors: contrast enhancement with hepatocyte-selective iodinated triglyceride versus conventional techniques.

PURPOSE: To compare findings at computed tomography (CT) enhanced with a hepatocyte-selective contrast agent (iodinated triglyceride) and/or iohexol and at CT during arterial portography (CTAP). MATERIALS AND METHODS: Rabbit livers were directly inoculated with VX2 carcinoma. Results were compared for five helical CT examinations: unenhanced CT, iohexol-enhanced CT (600 mg iodine per kilogram of body weight [mg I/kg]), CTAP (with iohexol [600 mg I/kg]), triglyceride-enhanced CT (126 mg I/kg), and dual-contrast-enhanced CT (triglyceride plus iohexol [425 mg I/kg]). Attenuation of normal liver and tumor were compared with analysis of variance techniques and blinded reader evaluations. RESULTS: Normal liver attenuation was greatest at CTAP (127.3 HU +/- 5.3 [mean +/- standard error of the mean]), followed by dual-contrast-enhanced CT (112.4 HU +/- 1.2), iohexol-enhanced CT (97.9 HU +/- 2.2), triglyceride-enhanced CT (82.3 HU +/- 1.1), and unenhanced CT (54.9 HU +/- 1.8). Liver-to-lesion attenuation difference at triglyceride-enhanced CT was significantly greater than at iohexol-enhanced CT (P < .05), and attenuation differences at dual-contrast-enhanced CT were comparable to those at CTAP. Tumors did not enhance at triglyceride-enhanced CT, which increased conspicuity. Sensitivity values for lesion detection at dual-contrast-enhanced CT were greater than those at iohexol-enhanced CT or at CTAP (P < .05). CONCLUSION: At CT enhanced with triglyceride (especially when combined with iohexol), sensitivity values and liver-to-lesion attenuation differences were greater with lower iodine doses than with iohexol or at CTAP.

Animals↗
PubMed1997

Contrast media-associated nephrotoxicity.

Contrast media-associated nephrotoxicity (CM-AN) continues to be a common cause of hospital-acquired acute renal failure. This review of CM-AN discusses the pathogenesis, clinical features, incidence, risk factors with an emphasis on pre-existing renal insufficiency and diabetes mellitus, volume of contrast media, low osmolar versus high osmolar contrast media, and prophylaxis. Although the literature contains an abundance of information concerning CM-AN, areas of uncertainty remain in respect to clinical significance, risk with modem day radiological techniques and contrast media, optimal prophylactic regimens, and criteria for creatinine screening before contrast media administration.

Acute Kidney Injury↗
PubMed1996

Improving performance with clinical decision support.

BACKGROUND: CADU/CIS (Clinical and Administrative Decision-support Utility and Clinical Information System) is a clinical decision-support workstation that allows large volumes of clinical information systems data to be analyzed in a timely and user-friendly fashion. CARE PROCESS MEASUREMENT: For any given disease, subgroups of patients are identified, and automated, customized "clinical pathways" are generated. For each subgroup, the best practice norms for use of test and therapies are identified. Practice style variations are then compared to outcomes to focus inquiry on decisions that significantly affect outcomes. CASE STUDY: INTESTINAL OBSTRUCTION: Graduate Health Systems, a multisite integrated provider in the Philadelphia area, has used CADU/CIS to improve quality problems, reduce treatment-intensity variations, and improve clinical participation in care process evaluation and decision making. A task force selected intestinal obstruction without hernia as its first study because of the related high-volume and high-morbidity complications. Use of a ten-step method for clinical performance improvement showed that the intravenous administration of unnecessary fluids to 104 patients with intestinal obstruction induced congestive heart failure (CHF) in 5 patients. Task force members and other practicing physicians are now developing guidelines and other interventions aimed at fluid use. Indeed, the task force used CADU/CIS to identify an additional 250 patients in one year whose conditions were complicated by CHF. CONCLUSION: A clinical decision support tool can be instrumental in detecting problems with important clinical and economic implications, identifying their important underlying causes, tracking the associated tests and therapies, and monitoring interventions.

Aged↗
PubMed1996

Contrast media-associated nephrotoxicity.

Contrast media-associated nephrotoxicity continues to be a common cause of acute renal failure. We review recent developments in our understanding of the pathogenesis of this complication, focusing on the role of vasoactive substances which include adenosine, endothelium-derived relaxing factor, and endothelin. An overview of clinical features is presented with an emphasis on the value of low osmolar contrast media in azotemic patients. Prophylactic strategies are reviewed focusing on saline hydration alone, vasoactive pharmacological agents, theophylline, 'prophylactic hemodialysis', and possible differences in how these maneuvers affect diabetic and non-diabetic azotemic patients are discussed.

Contrast Media↗
PubMed1995

Effects of renal function on recainam pharmacokinetics and pharmacodynamics.

OBJECTIVES: To investigate the pharmacokinetics and pharmacodynamics of recainam, an investigational class I antiarrhythmic agent, in subjects with various degrees of renal function. METHODS: This single-dose open-label study was carried out at the Clinical Research Center of the University of Pennsylvania Hospital. Twenty-six volunteers participated in the study (group 1, glomerular filtration rate [GFR] < 15 ml/min; group 2, GFR 15 to 50 ml/min; group 3, GFR > 50 ml/min). After a single 400 mg oral dose, plasma samples were collected for the following 48 hours. Recainam pharmacokinetic parameters of apparent volume of distribution (Varea/F), apparent clearance (CL/F), elimination rate constant (ke), absorption rate constant (ka), lag-time (tlag), time to peak (tmax), and maximum concentration (Cmax) were determined with a least-squares regression program. The relationship between recainam concentrations and electrocardiographic intervals were determined with the sigmoidal maximum effect model. Measured GFR was correlated to CL/F with regression analysis. RESULTS: There were no significant differences found among groups in ka, tlag, tmax, and Varea/F. Significant differences were found in CL/F (114.4 +/- 32.7, 319.4 +/- 129.2, and 795.9 +/- 341.8 ml/min, group 1 versus group 3 and group 2 versus group 3, p < 0.05), Cmax (3.54 +2- 0.81, 1.77 +/- 0.53, and 1.63 +/- 0.66 micrograms/ml, group 1 versus group 2 and group 1 versus group 3, p < 0.01), and ke (0.074 +/- 0.025, 0.137 +/- 0.124, and 0.352 +/- 0.300, group 1 versus group 3, p < 0.05). Recainam CL/F was highly correlated with GFR (r = 0.67, p = 0.001). Approximately 8.9% +/- 3.8% of a recainam dose was eliminated during a 4-hour hemodialysis period. There was a trend (but not statistically significant) of increasing maximum percentage change in PR interval and the effective recainam concentration that produces half of its maximum effect (EC50) in group 1. CONCLUSION: Recainam dosing adjustment is required in renal impairment. Recainam is not dialyzed to a significant extent. Further studies are required to fully characterize the pharmacodynamic profile of recainam.

Administration, Oral↗