Biomedical subjects

T R Desai

Publications and source records attributed to T R Desai.

8 recordsLinked to original sources

PubMed2001

Patency and limb salvage after infrainguinal bypass with severely compromised ("blind") outflow.

HYPOTHESIS: Infrainguinal graft patency and limb salvage are adversely affected by severely compromised outflow. DESIGN: Retrospective review of all infrainguinal bypass procedures performed at a single institution during a 5-year period. SETTING: University teaching hospital. PATIENTS: Two hundred seventy-four patients underwent infrainguinal bypass for limb salvage (351 grafts in 307 limbs). INTERVENTIONS: All infrainguinal bypasses originated from a femoral artery. The distal anastomosis in 279 grafts was located in an artery with at least 1 patent outflow vessel with anatomically normal end-artery runoff (Society for Vascular Surgery/International Society for Cardiovascular Surgery ad hoc committee runoff score, 1-9). The distal anastomosis of 72 grafts was located in an artery with only collateral outflow ("blind bypass"; runoff score, 10). MAIN OUTCOME MEASURES: Perioperative morbidity and mortality, primary-assisted and secondary graft patency, limb salvage, and survival. RESULTS: All data are presented as mean +/- SEM. Patients undergoing blind bypass were older (age, 70 +/- 2 vs. 66 +/- 1 years; P <.05) and had a higher incidence of hypertension (90% vs 70%; P <.05) and end-stage renal disease (24% vs. 13%; P <.05). Comparing patients undergoing blind bypass to bypass with at least 1 patent outflow vessel, there were no differences in the use of nonautogenous conduits (50% vs 59%; P =.21) or postoperative warfarin (30% vs 32%; P =.69), or in perioperative mortality rates (2.7% vs 3.2%; P =.79). After a median follow-up of 13 months (range, 0-60 months), 2-year secondary graft patency for the entire group was 63% +/- 4%. The secondary patency rate of blind bypass grafts was no different from that of grafts with at least 1 patent outflow vessel (67% +/- 7% vs. 64% +/- 4%; P was not significant). However, the 2-year limb salvage rate in limbs with blind outflow was significantly worse than in limbs with at least 1 patent outflow vessel (67% +/- 7% vs. 76% +/- 3%; P =.04). CONCLUSION: Acceptable long-term patency rates can be achieved in infrainguinal bypass grafts with blind outflow, although blind outflow remains a marker for subsequent limb loss in the chronically ischemic leg.

Aged↗

PubMed2001

Long-term results justify autogenous infrainguinal bypass grafting in patients with end-stage renal failure.

INTRODUCTION: Infrainguinal bypass grafting for limb-threatening ischemia in patients with end-stage renal disease is generally thought to be associated with increased operative risk and poor long-term outcome. This retrospective study was undertaken to examine the modern-era, long-term results of infrainguinal bypass grafting in dialysis-dependent patients. METHODS: Over the past 5 years in a single institution, 425 lower extremities (368 consecutive patients) were revascularized for the indication of limb salvage. Sixty-four patients (82 limbs) were dialysis-dependent at the time of revascularization, and this group was analyzed separately. They exhibited statistically significant higher incidences of diabetes (83% vs 56%; P <.001), hypertension (91% vs 74%; P <.001), and more distal vascular disease, which required a greater proportion of proximal anastomoses at the popliteal level (24% vs 11%; P <.01) and distal anastomoses at the infrapopliteal level (75% vs 65%; P <.05). RESULTS: Despite the higher prevalence of comorbid conditions and distal disease in patients with renal failure, their perioperative 30-day mortality rate remained low (4.9%) and was not significantly different from that in patients with functioning kidneys (2.9%; P = not significant). After a median follow-up of 11 months (range, 0-60 months), the 3-year autogenous conduit secondary graft patency in patients with renal failure was no different than in patients with functioning kidneys (67% +/- 9% vs 64% +/- 5%; P = not significant). Nonautogenous conduits in dialysis-dependent patients exhibited a significantly poorer outcome with only 27% +/- 12% remaining secondarily patent at 2 years. As expected, both limb salvage and patient survival were significantly less in patients with renal faiture, although both exceeded 50% at 3 years (limb salvage 59% +/- 8% vs 68% +/- 5%; P <.05; patient survival 60% +/- 8% vs 86% +/- 4%; P <.001). The often-quoted phenomenon of limb loss, despite a patent bypass graft, occurred infrequently in this study (n = 3 of 82 limbs). CONCLUSION: Infrainguinal revascularization can be performed in dialysis-dependent patients with acceptable perioperative and long-term results, especially in patients in whom adequate autologous conduit is available.

Blood Vessel Prosthesis Implantation↗

PubMed2000

Angioplasty does not affect subsequent operative renal artery revascularization.

BACKGROUND: Although increased application of percutaneous renal artery angioplasty and stenting has facilitated nonoperative renal revascularization, patient outcomes after failed angioplasty are not established. METHODS: Renal artery revascularization was performed in 31 patients (38 arteries) from 1993 to 1999. Twenty patients underwent primary surgical repair, and 11 patients underwent secondary reconstruction after angioplasty (n = 7) or angioplasty and stenting (n = 4). Before operation, all patients had severe hypertension (blood pressure 166+/-5.2/92 +/- 2.7 mm Hg) that required an average of 3.0 +/- 0.2 medications for control. In addition, 12 patients (primary 45% vs secondary 27%; P = NS) had evidence of renal insufficiency (creatinine > or =1.7 mg/dL). RESULTS: There was no difference between primary and secondary procedures in the length of hospital stay (12+/- 1.4 vs. 12+/-3.2 days; P = NS), major morbidity (10% vs. 18%; P = NS) or perioperative mortality (overall mortality 2 of 31; primary 5% vs secondary 9%; P = NS). The majority of patients demonstrated improvement or cure of hypertension (primary 94% vs secondary 90%; P = NS) and stable or decreased creatinine (primary 74% vs secondary 82%; P = not significant). Overall survival (mean follow-up 22+/-3.5 months) was 89%+/-5.7%. CONCLUSIONS: Although this surgical series does not address the true outcomes of renal artery angioplasty, the results suggest that renal artery angioplasty does not prejudice subsequent surgical outcomes in patients who are carefully followed after angioplasty.

Adolescent↗

PubMed1999

Decrease in mucosal alkaline phosphatase: a potential marker of intestinal reperfusion injury.

Intestinal ischemia necessitates rapid re-establishment of blood flow to prevent irreversible anoxic tissue damage. However, reperfusion results in additional injury as a consequence of the generation of oxygen free radicals. To date, no clear-cut marker to differentiate between ischemia versus reperfusion injury is available. In this regard, previous studies from our laboratory utilizing a rat in vitro lipid peroxidation model demonstrated that the generation of free radicals resulted in the inactivation of only the intestinal brush border alkaline phosphatase enzyme, with no effect on other membrane-bound digestive enzymes. Current studies were designed to assess the possibility of alkaline phosphatase being a specific marker of the reperfusion injury in canine and human ex vivo ischemia/reperfusion models. Small bowels harvested from canines and organ donors were subjected to ischemia followed by reperfusion. Brush border membrane enzymes, alkaline phosphatase, sucrase, maltase, and gamma-glutamyl transpeptidase were assayed in mucosal extracts from intestines with ischemia versus reperfusion. In both experimental models, there was no change in any enzyme activity with warm ischemia alone. In contrast, alkaline phosphatase activity was significantly decreased in both the canine and human reperfusion models, with no change in specific activities of sucrase, maltase, and gamma-glutamyl transpeptidase. Our data indicate that the alkaline phosphatase enzyme activity may represent a potential marker of intestinal reperfusion injury and may permit quantitative assessments of therapeutic interventions in human intestinal reperfusion injury.

Alkaline Phosphatase↗

PubMed1996

Mechanisms of neurologic deficits and mortality with carotid endarterectomy.

OBJECTIVE: To evaluate the incidence and etiology of perioperative complications of carotid endarterectomy. DESIGN: Retrospective review of carotid endarterectomies performed over 13 years. Risk factors, indications, results of electroencephalographic (EEG) monitoring, and outcomes were evaluated. SETTING: University medical center. PATIENTS: Three hundred sixty-seven consecutive primary carotid endarterectomies were performed on 336 patients. Indications for operation included transient ischemic attack (48.5%), asymptomatic stenosis (24%), stroke (17%), nonlateralizing ischemia (9.5%), and stroke-in-evolution (1%). MAIN OUTCOME MEASURES: Postoperative neurologic deficits (permanent and transient) and deaths were correlated with preoperative symptoms, probable mechanism of the neurologic event, intraoperative EEG changes, and the use of intraoperative shunts. RESULTS: Four new permanent neurologic deficits (1.1%) and one transient postoperative deficit were noted. Of the five deficits, three were related to undiagnosed intraoperative cerebral ischemia and two were related to perioperative emboli. Three perioperative deaths (0.8%) occurred: two of myocardial infarction and one of an intracerebral hemorrhage from a ruptured arteriovenous malformation. Intraoperative EEG tracings for the most recent consecutive 175 procedures were analyzed. Shunts were used in 45 patients (26%), 38 of whom demonstrated significant EEG changes with carotid clamping. CONCLUSIONS: Carotid endarterectomy can be performed with a low risk of stroke (1.1%) and death (0.8%). Stroke was due to cerebral ischemia or embolization. With meticulous surgical technique, death is due to myocardial ischemia and not neurologic events.

Adult↗

PubMed1996

Physiologic concentrations of TNFalpha and IL-1beta released from reperfused human intestine upregulate E-selectin and ICAM-1.

Intestinal ischemia-reperfusion (I/R) causes local and distant tissue injury via neutrophil (PMN) activation and adhesion. Endothelial cell adhesion molecules (E-selectin, ICAM-1) mediate the adhesion and transmigration of PMN in the microcirculation. Expression of these receptors is influenced by cytokines. To determine the physiologic concentrations of two specific cytokines involved in I/R, tumor necrosis factor (TNF) and interleukin-1 (IL-1), human intestinal segments were exposed to 30 min of ischemia followed by reperfusion. Venous effluent samples were obtained; enzyme immunoassays measured maximum concentrations of TNF (30.5 +/ 1.0 pg/ml) and IL-1 (59.0 +/- 6.0 pg/ml). Cultured human endothelial cells were then exposed to physiologic concentrations of human recombinant TNF (10 pg/ml) and IL-1 (10 pg/ml), individually and in combination. Flow cytometric analysis of receptor expression demonstrated upregulation of E-selectin as early as 2 hr (P < 0.05) with maximum effects at 4 hr. At 4 hr, E-selectin expression (% shift from baseline) was greater with TNF and IL-1 combined (50.9 +/- 2.9, P < 0.01) than with either cytokine alone (TNF 34.6 +/- 4.0; IL-1 23.5 +/- 4.0, P < 0.01). ICAM-1 receptor expression began at 4 hr with maximum effects at 24 hr. ICAM-1 expression after TNF and IL-1 exposure (15.4 +/- 1.3, P < 0.001) was also greater than TNF (10.9 +/- 0.3, P < 0.01) or IL-1 (3.1 +/- 1.5) alone. TNF and IL-1 are present in venous effluent in concentrations capable of increasing PMN adhesion in the microcirculation. These findings support a role for these cytokines in local and distant organ injury from I/R. Since combined effects are greater than either cytokine alone, antagonism of both TNF and IL-1 may be required for a therapeutic benefit in clinical applications.

Cells, Cultured↗

PubMed1996

Defining the critical limit of oxygen extraction in the human small intestine.

Although animal models have been used to characterize the relation between oxygen consumption and blood flow, reliable data have not been generated in the human small intestine. We perfused segments of human small intestine by using an ex vivo perfusion circuit that allowed precise manipulation of blood flow and perfusion pressure. Our goal was to define the critical level of intestinal blood flow necessary to maintain the metabolic needs of the tissue. Human small intestine (n = 5) tissue obtained at transplantation harvest was transported on ice to the laboratory. A 40-cm mid-jejunal segment was selected for perfusion, and appropriate inflow and outflow vessels were identified and cannulated. Perfusion with an autologous blood solution was initiated through an extracorporeal membrane oxygenation circuit. After a 30-minute equilibration period, arterial and venous blood gases were measured at varying flow rates while maintaining a constant hematocrit level. Arterial and venous oxygen content, arteriovenous oxygen difference (A-VO2 diff), and oxygen consumption (VO2) were then calculated. Our results demonstrated that at blood flows > 30 ml/min/100 g, VO2 is independent of blood flow (1.6 +/- 0.06 ml/min/100 g), and oxygen extraction is inversely related to flow. Below this blood flow rate of 30 ml/min/100 g, oxygen extraction does not increase further (6.3 +/- 0.3 vol%), and VO2 becomes flow dependent. This ex vivo preparation defines for the first time a threshold value of blood flow for small intestine below which oxygen consumption decreases (30 ml/min/100 g). Previous animal studies have correlated such a decrease in oxygen consumption with functional and histologic evidence of tissue injury. This "critical" flow rate in human intestine is similar to that found previously in canine and feline intestine, but lower than that of rodent species.

Animals↗

PubMed1995

Endothelial cell response to hypoxia-reoxygenation is mediated by IL-1.

Reperfusion injury involves the adhesion and activation of neutrophils (PMN) both in affected tissues and distant organs. Cell adhesion molecules (CAM) such as endothelial-leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) are known to mediate, at least in part, the adherence of activated PMN to the endothelium. To characterize the cellular mechanisms of this phenomenon, we exposed cultured human umbilical vein endothelial cells (HU-VEC) to hypoxia and reoxygenation (H/R) using an incubator chamber purged of oxygen with 100% nitrogen. Confluent monolayers of HUVEC were subjected to 60 min of hypoxia followed by variable periods of reoxygenation (120 and 240 min). Flow cytometry was utilized to assess the expression of ELAM-1 and ICAM-1, expressed as percent shift from baseline expression. To determine what role endothelium-derived cytokines such as IL-1 play in the expression of CAM after H/R, we performed additional experiments in the presence of recombinant IL-1 receptor antagonist (IL-1RA). ICAM-1 was present on unstimulated HUVEC while ELAM-1 was not constitutively expressed. Following exposure of cells to hypoxia and reoxygenation, significant increases in ELAM expression were seen (8.4 +/- 2.4% at 120 min; 19.1 +/- 7.4%, P < 0.05). While there was similar trend in ICAM expression, this did not achieve statistical significance (0.10 < P < 0.05). The addition of IL-1RA (10 ng/ml) to hypoxic HUVEC consistently attenuated ELAM-1 upregulation during reoxygenation (0.8 +/- 0.7% at 120 min and 5.9 +/- 4.1% at 240 min) such that expression was not significantly greater than baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion Molecules↗