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Biomedical subjects

D J Goldstein

Publications and source records attributed to D J Goldstein.

At least 37 records · Page 2Linked to original sources
PubMed1999

Current status and future directions of minimally invasive cardiac surgery.

The impetus to reduce the trauma of surgery witnessed over the past decade in all fields of surgery has recently extended into the cardiac surgical arena; however, unlike other specialties, the invasiveness of cardiac surgery can be reduced by limiting the size of incisions and by avoiding cardiopulmonary bypass. This article reviews the rationale, clinical experience, and outcomes of the minimally invasive approaches to cardiac surgery that have evolved over the past 2 years and glimpses into the future of this rapidly evolving field.

Cardiac Surgical Procedures↗
PubMed1999

Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age.

OBJECTIVE: Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease. The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age. METHODS: Study participants were 118 very low birth weight infants who, at 15 to 25 days of life, were not weaning from assisted ventilation and were then enrolled in a randomized, placebo-controlled, double-blind trial of a 42-day tapering course of dexamethasone. Infants were examined at 1 year of age, adjusted for prematurity, by a pediatrician and a child psychologist. A physical and neurologic examination was performed, and the Bayley Scales of Infant Development were administered. All examiners were blind to treatment group. RESULTS: Groups were similar in terms of birth weight, gestational age, gender, and race. A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography (21% vs 11%). Group differences were not found for Bayley Mental Development Index (median [range] for dexamethasone-treated group, 94 [50-123]; for placebo group, 90 [28-117]) or Psychomotor Development Index Index (median [range]) for dexamethasone-treated group, 78 (50-109); for placebo-treated group, 81 [28-117]). More dexamethasone-treated infants had cerebral palsy (25% vs 7%) and abnormal neurologic examination findings (45% vs 16%). In stratified analyses, adjusted for major cranial ultrasound abnormalities, these associations persisted (OR values for cerebral palsy, 5.3; 95% CI: 1.3-21.4; OR values for neurologic abnormality 3.6; 95% CI: 1.2-11.0). CONCLUSIONS: A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy. Possible explanations include an adverse effect of this therapy on brain development and/or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury.

Cerebral Palsy↗
PubMed1999

Colonic obstruction due to sigmoid muscular hyperplasia.

We report a case of acute colonic obstruction initially presumed to be secondary to acute diverticulitis, necessitating emergent surgical intervention. Pathologic examination failed to reveal evidence of inflammation, fibrosis or neoplasia. Marked hypertrophy of the sigmoid circular muscle layer was documented and thought to be the etiology of the colonic obstruction.

Acute Disease↗
PubMed1998

ErbB-4 ribozymes abolish neuregulin-induced mitogenesis.

The epidermal growth factor-like receptor tyrosine kinase (ErbB) family is frequently overexpressed in a variety of human carcinomas, including breast cancer. To assist in characterizing the role of ErbB-4 in breast cancer, we generated three specific hammerhead ribozymes targeted to the ErbB-4 mRNA. These ribozymes, Rz6, Rz21, and Rz29, efficiently catalyzed the specific cleavage of ErbB-4 message in a cell-free system. We demonstrated that the neuregulin-induced mitogenic effect was abolished in ribozyme Rz29- and Rz6-transfected 32D/ErbB-4 cells. Inhibition of mitogenesis was characterized by ribozyme-mediated down-regulation of ErbB-4 expression. In addition, we provide the first evidence that different threshold levels of ErbB-4 expression and activation correlate with different responses to neuregulin stimulation. High levels of ErbB-4 expression, phosphorylation, and homodimerization are necessary for neuregulin-stimulated, interleukin 3-independent cell proliferation in the 32D/E4 cells. In the case of Rz29-transfected 32D/E4 cells, low levels of ErbB-4 expression allowed neuregulin-induced phosphorylation but were insufficient to couple the activated receptor to cellular signaling. Furthermore, expression of the functional ErbB-4 ribozyme in T47D human breast carcinoma cells led to a down-regulation of endogenous ErbB-4 expression and a reduction of anchorage-independent colony formation. These studies support the use of ErbB-4 ribozymes to define the role of ErbB-4 receptors in human cancers.

Animals↗
PubMed1998

Transthoracic, transdiaphragmatic excision of simultaneous lung and adrenal lesions.

Simultaneous adrenal and pulmonary lesions frequently present a therapeutic challenge to the thoracic surgeon. We describe 2 cases in which a transthoracic, transdiaphragmatic approach was used to establish tissue diagnosis and complete removal of gross tumor. In 1 case an intraoperative decision to perform a pneumonectomy was dictated by the tissue diagnosis of the adrenal mass, which was obtained with relative ease via this method. In both cases the morbidity of traditional approaches for adrenal operation was avoided.

Adrenal Gland Neoplasms↗
PubMed1998

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure.

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.

Animals↗
PubMed1998

The hemodialysis pilot study: nutrition program and participant characteristics at baseline. The HEMO Study Group.

OBJECTIVE: Describe the nutrition program (assessments and interventions) and the participants' baseline nutritional characteristics in the Hemodialysis Pilot Study. DESIGN: Cross sectional survey in which hemodialysis patients were examined during 10 weeks of baseline (BL), before randomization study interventions (dose and flux). SETTING: Four hemodialysis centers (eight dialysis units in total). PATIENTS: Twenty-nine male (mean age, 63 years; range, 34 to 75) and 20 female (mean age, 61 years; range, 29 to 73) hemodialysis patients. INTERVENTIONS: None during BL. MAIN OUTCOME MEASURES: Feasibility of implementing the proposed nutrition program before conducting the full-scale trial, and description of baseline characteristics related to nutrition. RESULTS: A nutrition program was developed to assess nutritional status during BL and follow-up periods and to intervene in patients with weight loss or decreasing serum albumin. Methods for collecting biochemical, dietary and anthropometric data were implemented at four clinical centers. At baseline, mean protein intake estimated by single pool normalized protein catabolic rate was 0.95 +/- 0.21 gm/kg adjusted body weight (ABW) (n = 42) and by diet record assisted recalls (n = 47) 0.94 +/- 0.36 gm/kg ABW/d, respectively. Mean energy intake was 22.8 +/- 8 kcal/kg ABW/day (n = 39). Mean serum albumin concentration using the bromcresol green method was 3.8 +/- 0.4 gm/dL (n = 40). Mean body mass index was within the normal limits of 19-27 kg/m2. Mean skinfold thicknesses in females, but not males, were shifted toward the lower end of usual distributions for healthy individuals. CONCLUSIONS: The goal of designing, developing, and implementing the diet and nutrition component, and related data collection for the HEMO pilot study was accomplished at four separate clinical centers. Baseline mean protein and energy intake were low, suggesting that continuing dietary surveillance is needed. The ongoing full-scale HEMO study will provide the first prospective analysis of dietary intake, nutritional status, and outcome in maintenance hemodialysis patients as a function of dialysis dose and membrane flux.

Adult↗
PubMed1998

Outpatient pacemaker procedures in orally anticoagulated patients.

Reexamination of surgical practices in the present era of cost containment has led to increased outpatient procedures including pacemaker surgery. While the safety and economic benefits of outpatient pacemaker surgery in nonanticoagulated patients is well documented, results of pacemaker operations in patients maintained on coumadin for thromboembolic prophylaxis have not been evaluated. In patients where complications with pacemaker surgery appeared successive, we have established a low incidence of complications. Recently, we extended this approach to the outpatient setting; this report retrospectively reviews our 4-year experience. During the study period, 150 patients underwent outpatient pacemaker procedures, including 37 patients receiving oral warfarin. There was no difference in the incidence of wound related and wound unrelated complications between patients receiving warfarin and the nonanticoagulated cohort. In addition, no wound hematomas, blood transfusions, or clinically significant bleeding episodes were noted among warfarin recipients. We conclude that pacemaker surgery in patients receiving oral anticoagulation is safe and feasible. The use of the cephalic cutdown technique avoiding blind subclavian punctures, meticulous attention to pocket hemostasis, and the use of small caliber unipolar positive fixation leads appears warranted in this selected group of patients at high risk for perioperative bleeding.

Administration, Oral↗
PubMed1998

Strategies for nutritional intervention in patients with renal failure.

This review article discusses the evidence documenting the interrelationship between nutritional status and clinical outcome of the renal patient population. The limitations of accurately assessing the nutritional status of this patient group with commonly used indices are detailed. An overview of the history of nutrition supplementation as an intervention for the malnourished renal patient reveals that the efficacy of both enteral and parenteral methods has not been adequately explored to draw any firm conclusions. Based on available data, recommendations for providing nutrition care for the malnourished patient are provided. Therapeutics that are currently under investigation as future interventions for malnutrition are identified.

Enteral Nutrition↗
PubMed1997

Activation of the focal adhesion kinase signal transduction pathway in cervical carcinoma cell lines and human genital epithelial cells immortalized with human papillomavirus type 18.

The inappropriate activation of protein-tyrosine kinases (PTKs) has been associated with initiation and progression of several types of human cancers. We therefore postulated that immortalization by DNA tumor viruses results in the induction of PTKs fundamental to these processes. An RT-PCR-based screen was thus used to identify PTKs that were abundantly expressed in HPV-18-immortalized epithelial cells and HPV-containing carcinoma cell lines. One of the genes isolated in this screen was the focal adhesion kinase (FAK; pp125FAK), a cytoplasmic protein kinase that is activated in v-src transformed cells or by stimulation with mitogenic polypeptides. FAK also becomes catalytically active upon integrin engagement with extracellular matrix proteins, such as fibronectin. We found that FAK expression and activity were significantly elevated in HPV-18 E6/E7-immortalized human genital epithelial cells relative to their primary cell counterparts. Protein expression and tyrosine phosphorylation of the putative FAK substrate, paxillin, were also notably increased upon HPV-18 immortalization of genital epithelial cells and in HPV-containing cervical carcinoma cell lines. Most significantly, these cells expressed markedly higher levels of both intracellular and extracellular fibronectin, thus providing a mechanism for activation of FAK and increased tyrosine phosphorylation of paxillin. These findings suggest a role for the integrin/FAK-mediated signaling pathway in cervical carcinogenesis and represent one of the first demonstrations of a tyrosine kinase whose activity is elevated following viral immortalization.

Cell Adhesion Molecules↗
PubMed1997

Bridge experience with long-term implantable left ventricular assist devices. Are they an alternative to transplantation?

BACKGROUND: If long-term use of left ventricular assist devices (LVADs) as bridges to transplantation is successful, the issue of permanent device implantation in lieu of transplantation could be addressed through the creation of appropriately designed trials. Our medium-term experience with both pneumatically and electrically powered ThermoCardiosystems LVADs is presented to outline the benefits and limitations of device support in lieu of transplantation. METHODS AND RESULTS: Detailed records were kept prospectively for all patients undergoing LVAD insertion. Fifty-eight LVADs were inserted over 5 years, with a survival rate of 74%. Mean patient age was 50 years, and duration of support averaged 98 days. Although common, both preexisting infection and infection during LVAD support were not associated with increased mortality or decreased rate of successful transplantation. Thromboembolic complications were rare, occurring in only three patients (5%) despite the absence of anticoagulation. Ventricular arrhythmias were well tolerated in all patients except in cases of early perioperative right ventricular failure, with no deaths. Right ventricular failure occurred in one third of patients and was managed in a small percentage by right ventricular assist device (RVAD) support and/or inhaled nitric oxide therapy. There were no serious device malfunctions, but five graft-related hemorrhages resulted in two deaths. Finally, a variety of noncardiac surgical procedures were performed in LVAD recipients, with no major morbidity and mortality. CONCLUSIONS: Over all, our medium-term experience with implantable LVAD support is encouraging. Although additional areas of investigation exist, improvements in patients selection and management together with device alterations that have reduced the thromboembolic incidence and facilitated patient rehabilitation lead us to believe that a prospective, randomized trial is indicated to study the role that LVADs may have as an alternative to medical management.

Aged↗
PubMed1997

Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression.

BACKGROUND: The salutary immunosuppressive effects of cyclosporine in extending cardiac allograft survival may be curtailed by its nephrotoxic effects. We reviewed our first 9 years of experience with cyclosporine after cardiac transplantation, to evaluate the incidence and progression of cyclosporine-associated end-stage renal failure necessitating chronic hemodialysis. METHODS: Retrospective computer-based file review and personal interview when possible. RESULTS: The population at risk was comprised of all adult cardiac recipients surviving at least 3 years (n=293). Of these, 19 (6.5%) developed end-stage renal failure requiring chronic hemodialysis. There were 17 men and 2 women (mean age of 45 +/- 11 years). The mean creatinine clearance for the study group decreased by 38% (P<0.001 vs. before transplant) by 6 months after transplantation and by 48% by 3 years postoperatively (P<0.001 vs. before transplant). The mean serum creatinine rose by 80% (P< 0.001 vs. before transplant) by 6 months after transplantation and by 125% by 3 years postoperatively (P<0.001 vs. before transplant). Time elapsed from transplantation to hemodialysis ranged from 3.7 to 9.5 years (mean 6.4 +/- 2). Actuarial 1- year survival after onset of hemodialysis was 75%. CONCLUSIONS: Although cyclosporine remains the central immunosuppressive agent for cardiac allograft recipients, its use leads to a greater than one-third decrease in creatinine clearance by 6 months after transplantation and progression to end-stage renal failure, requiring hemodialysis in 6.5% of cardiac transplant recipients. Moreover, these patients are at increased risk of death compared with other cardiac allograft recipients. This data warrants the search of alternative or adjunctive agents that would allow decreased dosing or reduced nephrotoxicity of cyclosporine, while maintaining equivalent survival.

Adult↗
PubMed1997

Circulatory resuscitation with left ventricular assist device support reduces interleukins 6 and 8 levels.

BACKGROUND: Elevated tumor necrosis factor serum levels have been reported in patients with severe congestive heart failure. This study was designed to characterize the cytokine profile in patients with acute circulatory collapse. METHODS: Blood drawn from 14 consecutive patients within 24 hours before undergoing left ventricular assist device placement and after at least 30 days of mechanical assistance or before transplantation was assayed for levels of interleukin 6, interleukin 8, and tumor necrosis factor-alpha. RESULTS: Interleukin 6 level was elevated in 11 (79%), interleukin 8 in 10 (71%), and tumor necrosis factor in 2 (14%) of the 14 patients. After hemodynamic recovery, interleukin 6 levels decreased from 33.6 +/- 9 pg/mL to 11.3 +/- 4 pg/mL (p = 0.05) and interleukin 8 levels decreased from 122 +/- 34 pg/mL to 19.7 +/- 8 pg/mL (p = 0.005). Tumor necrosis factor-alpha levels did not vary significantly; they were associated with infection in 2 left ventricular assist device recipients and normalized after left ventricular assist device support. All patients had resolution of circulatory shock after mechanical support and had improvement in parameters of end-organ function. CONCLUSIONS: Circulatory shock treated with left ventricular assist device placement is associated with a proinflammatory response similar to that seen in septic shock. The decrease in cytokine serum levels that follows hemodynamic recovery suggests that these cytokines may be markers of tissue damage and may modulate cardiac dysfunction.

Biomarkers↗
PubMed1997

Mitral valve replacement and tricuspid valve repair after cardiac transplantation.

Efforts aimed at limiting the pool of cardiac retransplantation candidates have focused increasingly on attempts to preserve cardiac allograft function. The present report reviews the course of a patient who underwent mitral valve replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac transplantation and examines the limited reported world experience with valve replacement after transplantation. The limited yet successful experiences with these and other operations in cardiac allograft recipients suggest that worsening donor organ shortages will likely lead to increased clinical experience with conventional operations in the transplanted heart.

Cardiomyopathy, Dilated↗