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Biomedical subjects

S Keshavjee

Publications and source records attributed to S Keshavjee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Giant bronchial carcinoid tumors: a multidisciplinary approach.

BACKGROUND: Bronchial carcinoid tumors account for approximately 2% of all lung tumors. Although they were considered benign lesions, they are now categorized malignant, occasionally with poor prognosis. The clinical symptoms can be highly variable and are often present for many years before diagnosis. Whereas some carcinoids are entirely asymptomatic, others are accompanied by carcinoid or paraneoplastic syndromes. METHODS: We describe the multidisciplinary management of a 34-year-old female patient with a massive actively secreting bronchial carcinoid tumor of the right lung. Furthermore, we provide a review of the literature regarding the operative treatment and the perioperative management of pulmonary carcinoid tumors with respect to surgical, anesthetic, radiologic, and pathologic considerations. RESULTS: In the reported case, the first symptoms were chronic watery diarrhea, skin flushing, progressive shortness of breath, and increasing right shoulder pain. When the patient initially presented at our institution, the tumor had already reached an enormous size and it involved the right and left atrium as well as the atrial septum. Using an evidence-based, multidisciplinary approach the patient was treated successfully with extended surgical resection. CONCLUSIONS: Carcinoid tumors are potentially curable even if they reach a significant size and thus an aggressive strategy is warranted. The management of such cases requires careful investigation, planning, and treatment with collaborative expertise provided by a multidisciplinary team. We demonstrated that this approach can lead to a favorable outcome in what first appeared to be a formidable and unresectable tumor.

Adult↗
PubMed2001

Raffinose improves 24-hour lung preservation in low potassium dextran glucose solution: a histologic and ultrastructural analysis.

BACKGROUND: We have previously shown that the addition of raffinose to low potassium dextran (LPD) preservation solution improves transplanted rat lung function after 24 hours of storage. The mechanisms by which raffinose acts are unclear. The aim of this study was to examine the histologic and ultrastructural correlates of this enhanced pulmonary function after preservation with raffinose. METHODS: In a randomized, blinded study, rat lungs were flushed with LPD, or LPD containing 30 mmol/L of raffinose, and stored for 24 hours at 4 degrees C. Control lungs were flushed with LPD but not stored (n = 5 each group). Changes in postpreservation edema were determined. In addition, lungs were flushed with a trypan blue solution to quantify cell death, and examined using both light and electron microscopy. RESULTS: The LPD lungs gained significantly more weight (25.5%+/-5.5%) compared with raffinose-LPD lungs (5.2%+/-5.3%; p < 0.0001). There were higher percentages of dead cells in the LPD lungs (29%+/-0.3% of total cells) compared with raffinose-LPD lungs (14%+/-1.4%; p < 0.001) and control lungs (0.2%+/-5%; p < 0.001). Control lungs maintained normal ultrastructure, whereas LPD lungs showed a decreased number of intact type II pneumocytes and significant cellular necrosis. Interstitial and alveolar edema with interstitial macrophage infiltration was also observed. Alveolar capillaries were collapsed. In contrast, raffinose-LPD lungs showed only mild alterations such as minimal interstitial edematous expansion, fewer damaged cells, and minimal capillary injury. CONCLUSIONS: Raffinose exerts a cytoprotective effect on pulmonary grafts during preservation, which explains the previously documented improved function. This simple modification of LPD with raffinose may provide clinical benefit in extended pulmonary preservation.

Animals↗
PubMed2001

Medicine betrayed: hemophilia patients and HIV in the US.

The contamination of blood products by HIV in the early 1980s resulted in thousands of deaths among people with hemophilia in the United States and elsewhere. In the US, industry, government, physicians, and advocacy groups were implicated in this tragedy. In response to pleas from members of the US hemophilia community, the Institute of Medicine (IOM) of the National Academy of Science convened a public hearing to identify the institutional determinants of the HIV/AIDS epidemic among US hemophilia patients. The resulting IOM Report (1995) established a narrative of the crisis and indicated necessary improvements to the management of the US blood supply. The Report, however, failed to address the hemophilia community's demands for accountability and retribution. In this paper we explore the moral and social dimensions of this tragedy through narrative analysis of the original testimonies of hemophilia sufferers, interviews with some patients and their families, and a re-examination of the text of the IOM Report itself. We examine the process by which this crisis was addressed--through the discourses of science and law--and how it was ultimately framed as a failure of management and oversight rather than a moral failure of the for-profit health-care system. Thus, while the Report and its aftermath demonstrate powerfully how testimonials of suffering can influence public policy, by not addressing what is at stake for the victims--failure to protect patients in an era of increasingly commodified health care--it led to an exculpatory solution that obfuscated the moral dimensions of suffering.

Anecdotes as Topic↗
PubMed2001

Long-term survival after multiple resections of a fibrosarcoma involving the lung and chest wall.

We report on the case of a 61-year-old male patient who developed a giant fibrosarcoma involving both the lung and chest wall. This patient underwent three extended resections including the chest wall in each case. Radiotherapy was administered after the last resection, when the tumor was obviously not completely removed. The patient lives a normal life with no signs of recurrence 5 years after his last resection. Multiple extended resections of large and aggressive sarcomas can result in long-term survival, with good quality of life, in adequately selected patients.

Fibrosarcoma↗
PubMed2001

Hemodynamic unloading leads to regression of pulmonary vascular disease in rats.

OBJECTIVE: Treatment options for patients with advanced pulmonary vascular disease caused by a congenital heart defect are still mainly limited to heart-lung transplantation or lung transplantation with repair of the cardiac lesion. Because we have previously shown that the structural changes associated with pulmonary hypertension can be reversed by stress unloading in an organ culture model, we now investigate whether hemodynamic unloading will lead to regression of pulmonary vascular disease in the intact animal. METHODS: Right middle and lower lobectomy and monocrotaline injection were performed in Lewis rats (n = 22) to cause pulmonary vascular disease from a combined hemodynamic and toxic injury. Twenty-eight days later the left lungs were examined (n = 10) or exposed to normal pulmonary artery pressure for an additional 14 (n = 5) or 28 (n = 7) days by transplantation into healthy recipients. Pulmonary artery pressure, ventricular weight, and pulmonary artery morphology were evaluated in each group. RESULTS: Pulmonary hypertension (50 vs 16 mm Hg; P <.001) and right ventricular hypertrophy (right ventricular/left ventricular weight 0.69 vs 0.32; P <.001) associated with pulmonary artery medial hypertrophy (28.2% vs 7.2% wall thickness; P <.001) and muscularization of small pulmonary arteries (92.3% vs 19.4%; P <.001) developed by day 28 (compared with untreated controls). However, transplantation into healthy recipients effectively unloaded the lungs (mean pulmonary artery pressure 17 and 24 mm Hg at 14 and 28 days after transplantation) and resulted in progressive normalization of medial hypertrophy (15.6% and 12.1% at 14 and 28 days) and muscularization (65.1% and 42.2% at 14 and 28 days) relative to nontransplanted controls (P <.005 in each case). CONCLUSIONS: Hemodynamic unloading of lungs with pulmonary vascular disease results in progressive normalization of pulmonary artery structure. These results are the first to provide a rationale for attempting to induce regression of pulmonary vascular disease by pressure unloading of the pulmonary circulation. Methods to mechanically unload the pulmonary circulation should be critically evaluated as a strategy for staged surgical repair of congenital heart defects despite presumed irreversible pulmonary hypertension.

Animals↗
PubMed2001

Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation.

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.

Adult↗
PubMed2000

Ischemia reperfusion-induced dynamic changes of protein tyrosine phosphorylation during human lung transplantation.

BACKGROUND: We have recently demonstrated that more than 20% of lung cells undergo apoptosis within the first 2 hr of graft reperfusion after human lung transplantation. It has been found that changes of protein tyrosine phosphorylation are involved in the regulation of apoptosis in various cell types. METHODS: To determine the protein tyrosine phosphorylation status and related biochemistry changes, lung tissue biopsies were collected from six human lung transplant procedures after cold ischemic preservation (2-5 hr at 4 degrees C), after completing the implantation procedure (approximately 1 hr), and 1 or 2 hr after graft reperfusion. Western blotting was performed to determine protein tyrosine phosphorylation and several signal transduction proteins. Protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) activities were also measured. RESULTS: Protein tyrosine phosphorylation was significantly increased after lung implantation and before reperfusion, and significantly decreased during the first 2 hr of graft reperfusion. The activity of Src PTKs was reduced by 50% during graft reperfusion, which was associated with a decrease of Src proteins and human actin filament associated protein, a cofactor for Src activation. PTP activity significantly decreased after lung implantation and remained at a low level 1 hr after reperfusion. After 2 hr of reperfusion, however, PTP activity returned to the basal level. CONCLUSION: These dynamic changes of PTK and PTP likely explain the observed alterations of protein tyrosine phosphorylation. The significant decrease in protein tyrosine phosphorylation may be related to the observed apoptotic cell death during human lung transplantation.

Apoptosis↗
PubMed2000

Heparin interference with reverse transcriptase polymerase chain reaction of RNA extracted from lungs after ischemia-reperfusion.

The reverse transcriptase polymerase chain reaction (RT-PCR) is a rapid and sensitive method for detecting gene expression. However, when we used this technique to study gene expression of cytokines in ischemic and ex-vivo-reperfused rat lungs as a model for transplantation, significant inhibition of RT-PCR reaction was observed. To optimize RT-PCR conditions, RNA was extracted from rat lungs after flushing, preservation, and reperfusion. RNA was further purified and PCR conditions were modified with various strategies. We found that heparinase I pretreatment completely overcame the inhibitory effects of RT-PCR using RNA extracted from lung tissues after ischemia-reperfusion. With this treatment, a dramatic increase in tumor necrosis factor-a (TNF-a) mRNA was revealed from lung tissues after ischemia-reperfusion. This result suggests that residual heparin in lung tissue interferes with RT-PCR. Because heparinization is routinely used during clinical and experimental organ transplantation, we recommend the treatment of RNA samples with heparinase prior to RT-PCR.

Animals↗
PubMed2000

Raffinose improves the function of rat pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

OBJECTIVES: The perfect strategy for pulmonary graft preservation remains elusive. Experimental work supports the use of perfusates, such as Euro-Collins, University of Wisconsin, and low-potassium dextran solutions. We use low-potassium dextran solution in our clinical program, but we aim for continued improvement. The trisaccharide raffinose has been shown to be responsible for the efficacy of University of Wisconsin perfusate in lung preservation. Raffinose is superior to a variety of other saccharides for this purpose. We tested the hypothesis that the addition of raffinose to low-potassium dextran solution might further improve graft function. METHODS: In a randomized blinded study with a rat left lung transplant model, donor lungs were flushed with either standard low-potassium dextran solution or low-potassium dextran solution modified by the addition of 30 mmol/L raffinose (n = 5 for each group). Alprostadil (prostaglandin E(1), 500 microg/L) was added to the perfusates in accordance with our clinical practice. Grafts were stored inflated at 4 degrees C for 24 hours. After transplantation, recipients were ventilated with a fraction of inspired oxygen of 1 and a positive end-expiratory pressure of 2 cm H(2)O. Graft function was evaluated by measuring oxygenation at 2 hours after graft reperfusion, peak airway pressure throughout the reperfusion period, and the wet/dry lung weight ratio. RESULTS: The group receiving low-potassium dextran solution with raffinose demonstrated significantly higher oxygenation (oxygen tension, 370 +/- 45 mm Hg vs 150 +/- 64 mm Hg; P =.0025), lower peak airway pressures at 2 hours after lung reperfusion (11 +/- 2.7 mm Hg vs 16 +/- 2.4 mm Hg; P <.001), and a lower wet/dry weight ratio (4.7 +/- 1.26 vs 11 +/- 5. 0; P =.017). CONCLUSION: Modification of low-potassium dextran solution with the trisaccharide raffinose resulted in a significant improvement in graft function in this model and merits further evaluation with respect to the mechanisms involved.

Animals↗
PubMed2000

Inhibition of angiotensin-converting enzyme by captopril: a novel approach to reduce ischemia-reperfusion injury after lung transplantation.

OBJECTIVES: Ischemia-reperfusion injury after lung transplantation involves the generation of free radicals. Captopril has been shown to be protective in models of ischemia-reperfusion injury in other organs by acting as a free radical scavenger. The purpose of this study was to assess the protective effects of captopril against ischemia-reperfusion injury and to evaluate the ability of captopril to scavenge free radicals and inhibit neutrophil activation in an experimental model of lung transplantation. METHODS: A rat single-lung transplant model was used. Donor lungs were flushed and preserved in low-potassium dextran-glucose solution with (n = 5) and without captopril (500 micromol/L; n = 5) for 18 hours at 4 degrees C and then transplanted and reperfused for 2 hours. At the conclusion of the 2-hour reperfusion period, arterial blood gases, blood pressure, and peak airway pressure were measured. Lung tissue biopsy specimens were obtained for assessment of wet/dry weight ratios, histology, and neutrophil sequestration (myeloperoxidase activity). Lipid peroxidation (F(2)-isoprostane assay) was analyzed from plasma samples and tissue lysates. RESULTS: The addition of captopril to the lung preservation solution significantly improved postreperfusion PO (2) (312 +/- 63.3 mm Hg vs 202 +/- 21.1 mm Hg; P =.006), peak airway pressure (11.4 +/- 1.1 cm H(2)O vs 15.6 +/- 1.5 cm H(2)O; P =.001), and wet/dry weight ratio (4.9 +/- 0.4 vs 15.8 +/- 10.9; P =.008). Blood pressures did not differ significantly between groups. No significant differences were seen in myeloperoxidase activity or F(2)-isoprostane levels. CONCLUSIONS: The use of captopril in the preservation solution ameliorates ischemia-reperfusion injury in transplanted lungs after an extended cold preservation period. The mechanisms by which captopril is protective remain elusive but do not appear to include inhibition of neutrophil sequestration or lipid peroxidation. This novel approach to ischemia-reperfusion injury may lead to improved lung function after transplantation and provide further insight into the pathogenesis of acute lung injury.

Angiotensin-Converting Enzyme Inhibitors↗