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Biomedical subjects

J Goldsmith

Publications and source records attributed to J Goldsmith.

At least 19 recordsLinked to original sources
PubMed1996

Polytetrafluoroethylene bypasses to infrapopliteal arteries without cuffs or patches: a better option than amputation in patients without autologous vein.

PURPOSE: This study was undertaken to evaluate our results of polytetrafluoroethylene (PTFE) tibial and peroneal artery bypasses done for limb salvage. METHODS: Within a group of patients undergoing infrainguinal limb salvage bypasses at our institution between January 1986 and May 1995, 63 patients faced an immediate amputation, had no autologous vein on duplex examination and operative exploration, and had only a tibial or peroneal artery as an outflow vessel for bypass. Most of these patients (82%) had two or more prior ipsilateral infrainguinal bypasses. These 63 patients underwent 66 PTFE bypasses to a tibial or peroneal artery without a distal anastomotic vein cuff or an adjunctive arteriovenous fistula. Our results were then compared with those reported from infrapopliteal (crural) bypasses performed with alternate autologous vein sources or PTFE in conjunction with various recommended adjuncts. RESULTS: The 3- and 5-year cumulative primary graft patency rates for our PTFE infrapopliteal bypasses were 39%+/-7% and 28%+/-9%, respectively. Secondary graft patency rates were 55%+/-8% and 43%+/-10% at 3 and 5 years, respectively. Limb salvage rates were 71%+/-7% at 3 years and 66%+/-8% at 5 years. Two-year actuarial patient survival rate was only 67%+/-7%. CONCLUSIONS: These results indicate that a PTFE bypass to an infrapopliteal artery remains a worthwhile option in patients without usable autologous vein. The secondary patency and limb salvage rates were acceptable in this setting and were not significantly different from the best results reported with prosthetic tibial/peroneal bypasses with distal vein cuffs or patches (74% at 1 year; 58% at 3 years), arteriovenous fistulas (71% at 1 year) or composite arm vein grafts (39% and 29% at 3 and 5 years, respectively).

Actuarial Analysis↗
PubMed1996

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.

Adolescent↗
PubMed1996

Macrophages during fibrosis following scleral fistulising surgery in a rat model.

PURPOSE: Glaucoma filtration surgery can fail in a minority of patients as a result of fibrosis in the subconjunctival bleb space and closure of the scleral fistula. In this study, the rat eye has been used as an experimental model for fistulising surgery in order to evaluate the clinical manifestation of bleb failure with the morphological events of the wound healing process. METHODS: A conjunctival bleb was successfully formed in 25 rats and was examined daily using slit lamp microscopy to evaluate postoperative inflammation and the presence of a bleb. At defined post-operative time points, serial frozen sections of eyes were stained immunohistochemically using a panel of monoclonal antibodies directed against known surface markers on rat immune/inflammatory cells. Positively stained cells were counted (a) in the bleb site, (b) at the sclerostomy and (c) at the suture site. RESULTS: Following an initial post-operative inflammation, a surgically formed sclerostomy and conjunctival bleb underwent a granulation and scarring response so that by 7-19 days the bleb had disappeared. Using the monoclonal antibodies applied in this study, it was possible to show that macrophages most likely play a major and pivotal role throughout the sequence of events that lead to repair of the fistula and closure of the bleb. It was also noted that the presence of an otherwise inert nylon suture used to close the incised conjunctiva can serve as a focus for macrophages. CONCLUSION: The rat has been successfully used as an experimental model of fistulising surgery and its subsequent failure. The use of a panel of monoclonal antibodies directed against specific surface markers on immune-inflammatory cells, highlighted macrophages to be prominent in all stages of this wound healing process.

Animals↗
PubMed1995

Prospective study of the value of prebypass saphenous vein angioscopy.

BACKGROUND: The patency of a saphenous vein graft is directly related to the quality of the vein harvested. Thus, appropriate evaluation of the vein before implanting it as a bypass graft may help identify those veins at high risk for early failure. Accordingly, we prospectively investigated whether prebypass angioscopic assessment of the saphenous vein could identify those vein grafts at particularly high risk of early failure. PATIENTS AND METHODS: Thirty-two greater saphenous veins with a grossly normal appearance were evaluated angioscopically before their use as a bypass conduit. After modification of abnormal segments, all of the veins irrigated well and were used as bypass grafts. RESULTS: Twenty-four patients were available for follow-up at 12 months. Seventeen (71%) had been prospectively classified as having angioscopically normal saphenous veins, while 7 were identified as having abnormal veins. The two groups did not differ significantly in demographics, cardiovascular risk factors, or indications for operative intervention. Twelve of the 17 (70%) normal veins were patent at 1 year; however, only 1 (14%) of the angioscopically abnormal vein grafts remained patent for 12 months (chi-square = 4.27; P = 0.039). CONCLUSION: Angioscopic inspection of the saphenous vein, before insertion as a graft, allows for identification of unrecognized venous disease that portends early graft thrombosis. Exclusion of abnormal veins, based on an abnormal angioscopic appearance, may lead to improved results for lower-extremity revascularization procedures; this supports the value of vein-graft angioscopy.

Angioscopy↗
PubMed1995

Transseptal defibrillation is superior for transvenous defibrillation.

The conventional electrode configuration of current internal defibrillation systems most commonly use superior vena caval (SVC) or combined SVC and subcutaneous (SC) electrodes as anode, and right ventricular apex (RVA) electrode as cathode. We have demonstrated earlier that the septal mass is important for defibrillation. The purpose of the present study was to compare a transseptal to a conventional electrode arrangement in the canine model. Three endocardial electrodes, 5 French EnGuard were positioned in RVA, SVC, and the right ventricular outflow (RVO) in eight dogs. A 5 French SC electrode was positioned in the fifth left intercostal space. RVA-RVO-/SC+ (configuration 2) was compared to SVC-SC+/RVA- (configuration 1). Defibrillation threshold testing was performed using asymmetrical biphasic shock, 6 msec+/2 msec-. Probit fit was used to compare the results at 40%, 50%, 60%, and 90% probabilities, and the logistic regression analysis to estimate the impact of variables. Electrode configuration had the strongest predictive value. Configuration 2 was superior to configuration 1 (P = 0.0016). At any voltage settings the probability of success for configuration 2 was greater, and current less (P < 0.00005). The energy requirements were reduced by approximately 33% for configuration 2. There were no significant differences in impedance between the two configurations. We conclude that transseptal defibrillation is more effective because of the improved lead geometry and voltage gradient.

Animals↗
PubMed1995

Electrode surface area is an important variable for defibrillation.

Previous studies have established efficacy of transseptal defibrillation. The purpose of the present study was to evaluate the role of transvenous electrode surface area for defibrillation. Sixteen dogs were randomized to 8 French and 5 French EnGuard electrodes; 8 dogs in each group. The length of the defibrillation coils was identical for both, but the surface area was different due to differences in the electrode diameters. Defibrillation threshold (DFT) testing was performed using a biphasic shock waveform, 6 msec+/2msec-. Logistic regression analysis was used to determine if the probability of defibrillation adjusted for voltage, current, and energy was different for 8 French electrodes. Logistic regression analysis found significant differences between 8 French and 5 French electrodes, with less voltage (P < 0.005), current (P < 0.03), and energy (P < 0.001) required at any level of probability to defibrillate for 8 French electrodes. These results support the conclusion that the surface area for endocardial electrodes is a significant factor for defibrillation. Therefore, when designing endocardial electrodes a desirable objective of reducing the electrode size should be weighed against the need to minimize DFTs.

Animals↗
PubMed1994

Squamous cell carcinoma antigen: clinical utility in squamous cell carcinoma of the uterine cervix.

This study further defines the clinical utility of squamous cell carcinoma antigen (SCC-Ag) in initial squamous carcinoma of the cervix, response to treatment, and in the detection of recurrence. Serum specimens were drawn and analyzed from patients with squamous cell carcinoma. Charts were reviewed on 272 patients with 1053 samples evaluated. Treatment of patients prior to the availability of the assay and patients lost to follow-up resulted in lower total numbers of initial and recurrent values. Data were analyzed to detect trends during and after treatment. All values at or above the lowest detectable level of antigen were included; that is, 1.5 ng/ml and above. A SCC-Ag value > or = 2.0 ng/ml drawn at any time during the disease process has a 96.3% positive predictive value, while a value < 2.0 ng/ml is 97.2% specific for absence of disease. Fifty-three percent of 103 patients had elevated SCC-Ag levels prior to treatment, with the proportion increasing accordingly with advancing stage at diagnosis. In 70 patients with recurrence, 81% had elevated values. Squamous cell carcinoma antigen predicted recurrence an average of 6.9 months prior to detection of clinically evident disease. Patients with initially negative SCC-Ag levels may demonstrate elevated values with tumor recurrence. This marker accurately reflects the response to treatment in patients who have elevated levels prior to treatment. Squamous cell carcinoma antigen is a useful tumor marker in the management of patients with squamous cell carcinoma of the uterine cervix.

Antigens, Neoplasm↗
PubMed1994

Eleven-year experience with tibiotibial bypass: an unusual but effective solution to distal tibial artery occlusive disease and limited autologous vein.

PURPOSE: The absence of sufficient length of suitable autologous vein occasionally prohibits the treatment of severe distal lower extremity arterial occlusive disease with a standard distal bypass originating from the common femoral artery. During the past 11 years, we have therefore selectively performed short distal bypasses originating from the infrapopliteal arteries in patients with limb-threatening ischemia and occlusive lesions limited to the distal tibial and peroneal arteries. This report summarizes our experience with these tibial artery based distal bypasses. METHODS: Forty-two distal lower extremity arterial bypasses originating from infrapopliteal arteries in 41 patients were performed over an 11-year period. Autologous vein was used as the bypass conduit in all cases. Extensions from a more proximal bypass were excluded. RESULTS: The primary patency rate of these tibiotibial bypasses was 77% at 1 year and 62% after 5 years. The limb salvage rate after 5 years was 74%. The perioperative mortality rate was low (2%), but the 5-year patient survival rate (64%) was similar to that with more standard lower extremity arterial reconstructive procedures. CONCLUSIONS: Tibiotibial bypass is an effective limb salvage procedure in carefully selected patients with distal tibial artery occlusive disease and limited autologous vein. It offers a durable means of distal revascularization in circumstances in which a standard operation might not be desirable or possible.

Adult↗
PubMed1994

Pharmacokinetic evaluation of the combination of zidovudine and didanosine in children with human immunodeficiency virus infection.

As part of a phase I/II trial in children infected with human immunodeficiency virus, we studied the pharmacokinetics of zidovudine and didanosine administered as single agents and in combination. Zidovudine (60 to 180 mg/m2 per dose) was given orally every 6 hours, and didanosine (60 to 180 mg/m2 per dose) every 12 hours. Pharmacokinetic samples were obtained from 54 patients and the area under the plasma concentration-time curve (AUC) was estimated by means of a previously defined limited sampling strategy. Follow-up blood samples were obtained after 4 and 12 weeks of treatment. The mean AUC for zidovudine ranged from 4.8 mumol.hr per liter at 60 mg/m2 to 11.0 mumol.hr per liter at the 180 mg/m2 level, and increased in proportion to the dose. The mean AUC for didanosine ranged from 2.8 mumol.hr per liter (60 mg/m2) to 8.0 mumol.hr per liter (180 mg/m2), with a wide interpatient variability. The AUCs of zidovudine and didanosine remained unchanged when the agents were administered in combination. There was no significant change in the AUCs of either drug after 4 and 12 weeks in comparison with those on day 3 of therapy. However, there was greater interpatient and intrapatient variability with didanosine than with zidovudine. These observations have implications for the future utility of therapeutic drug monitoring with these agents.

Adolescent↗
PubMed1994

Selective preservation of infected prosthetic arterial grafts. Analysis of a 20-year experience with 120 extracavitary-infected grafts.

OBJECTIVE: The authors report on their 20-year experience with 120 patients with infected extracavitary prosthetic arterial grafts (95 polytetraflouroethylene, 25 Dacron). Throughout this experience, an effort was made, when appropriate, to salvage all or a portion of these infected grafts. METHODS: When patients had arterial bleeding (20 cases) or systemic sepsis (6 cases), immediate graft excision was performed. When the infected graft was occluded (43 cases), subtotal graft excision was performed, leaving an oversewn 2- to 3-mm graft remnant to maintain patency of the artery. Complete graft preservation was attempted in 51 cases in which the graft was patent, the patient was not septic, and the anastomoses were intact. Aggressive operative wound debridement was repeated, as necessary, to achieve wound healing. The preferred method of revascularization, when necessary, included secondary bypasses tunneled through uninfected (often lateral) routes. Follow-up averaged 3 years (range, 1 month-20 years). RESULTS: This strategy resulted in a hospital mortality of 12% (14/120) and a hospital amputation rate in survivors of 13% (14/106 threatened limbs). Of the surviving patients treated by complete graft preservation, the hospital amputation rate was only 4% (2/45) and long-term complete graft preservation was successful in 71% (32/45) of cases. Partial graft preservation also proved successful in 85% (35/41) of surviving patients who had occluded grafts. Successful complete graft preservation was as likely when gram-negative or gram-positive bacteria were cultured from the wound, with the exception of Pseudomonas (successful graft preservation in only 40% [4/10] of cases). CONCLUSION: Based on this 20-year experience, the authors conclude that selective partial or complete graft preservation represents a simpler and better method of managing infected extracavitary prosthetic grafts than routine total graft excision.

Aged↗
PubMed1994

Effects of inhaled NO and inhibition of endogenous NO synthesis in oxidant-induced acute lung injury.

Inhaled nitric oxide (NO) decreases pulmonary arterial pressure (Ppa) and improves oxygenation in the adult respiratory distress syndrome. Endogenous NO can modulate the development of acute tissue injury. We investigated the effects of inhaled NO and of inhibition of endogenous NO synthase in oxidant-induced acute lung injury in the isolated buffer-perfused rabbit lung. A rapid (45 min) and a more gradual (3 h) model of oxidant-induced acute lung injury were developed using the production of superoxide free radicals from the reaction of purine with low and high doses of xanthine oxidase, respectively. The effects of rapid injury included increases in Ppa, precapillary pulmonary vascular resistance, capillary filtration coefficient (Kfc), and lung weight. In the gradual-injury model, only lung weight and Kfc increased. Pretreatment with inhaled NO (90-120 ppm) prevented the rise in Ppa and precapillary pulmonary vascular resistance in the rapid-injury model and prevented elevation of Kfc in the gradual-injury model. Pretreatment with an inhibitor of endogenous NO synthase (NG-nitro-L-arginine methyl ester) resulted in increased pulmonary capillary pressure and postcapillary pulmonary vascular resistance in the rapid-injury model and increased peak Ppa, pulmonary capillary pressure, and pulmonary vascular resistance in the gradual-injury model. These data suggest that in oxidant-induced acute lung injury 1) inhaled NO may attenuate increases in capillary permeability and 2) endogenous NO may function as a modulator of pulmonary vascular tone without affecting capillary permeability.

Administration, Inhalation↗
PubMed1993

Management of arterial injuries produced by percutaneous femoral procedures.

BACKGROUND: A significant number of vascular injuries occur with the use of percutaneous diagnostic and therapeutic procedures. This study was done to indicate the types of these injuries and their management. METHODS: Over a 30-month period, 55 patients required operation for vascular complications after percutaneous femoral procedures including infrarenal arteriography (six patients) and angioplasty (22 patients), coronary angiography (16 patients) and angioplasty (five patients), and aortic balloon pump insertion (six patients). RESULTS: The 14 iliac and 41 femoral artery injuries included 29 pseudoaneurysms, six lacerations with persistent bleeding, seven dissections, six occlusions, three ruptures, two arteriovenous fistulas, and two large hematomas. Control for all femoral and distal external iliac artery lesions was obtained solely through a groin incision in 45 (82%) patients. Our technique for exposure of the external iliac artery through the groin is described. A separate retroperitoneal incision was necessary in 10 patients because of proximal injury, massive pseudoaneurysm, morbid obesity, or heavily scarred groins. In this series 34 lateral suture repairs, 11 interposition or bypass grafts, four patch angioplasties, one endarterectomy, three thrombectomies, and two hematoma evacuations were performed. Although no limb loss occurred, we encountered nine wound complications, five myocardial infarctions, and two deaths. CONCLUSIONS: This experience shows the wide variety of vascular complications caused by percutaneous procedures and the different techniques necessary for their management.

Adolescent↗
PubMed1992

Management of infected lower extremity autologous vein grafts by selective graft preservation.

Between 1975 and 1991, we treated 16 patients with infected lower extremity autologous vein grafts performed for limb salvage by complete graft preservation. Traditional treatment of these infections includes immediate graft excision and complex revascularization procedures to prevent limb loss. The infection involved an intact anastomosis in 12 patients or the body of a patent graft in 4 patients. None of the patients was systemically septic. All patients were treated with appropriate intravenous antibiotics. Six patients were treated by placement of autologous tissue on the exposed graft (4 rotational muscle flaps, 2 skin grafts), and 10 were treated with antibiotic-soaked dressing changes and repeated operative débridements to achieve delayed secondary wound healing. This treatment resulted in a 19% (3 of 16) mortality rate and an 8% (1 of 13) amputation rate in survivors. Of the six patients managed by autologous tissue placement onto the infected graft, five patients had wounds that healed without complications, and one died of a myocardial infarction. Of the 10 patients treated by delayed secondary wound healing, 2 developed anastomotic hemorrhage, which resulted in death in 1 patient and above-knee amputation in the other, 1 died of a myocardial infarction, 1 developed graft thrombosis, and 6 had wounds that healed. Placement of autologous tissue to cover an exposed, infected patent vein graft with intact anastomoses may prevent graft dessication, disruption, and thrombosis, which renders graft preservation an easier, safer method of treatment compared with routine graft excision.

Aged↗