Biomedical subjects

K Parekh

Publications and source records attributed to K Parekh.

5 recordsLinked to original sources

PubMed2004

Use of cyclosporine in lung transplantation.

Prior to the cyclosporine (CsA) era, there were no long-term survivors from lung transplantation as the immunosuppressive drugs made patients very susceptible to opportunistic infections and anastomotic complications. CsA is a calcineurin inhibitor that binds to cyclophilins and inhibits transcription of interleukin 2 in T cells, thereby preventing proliferation of activated T cells. The initial immunosuppressive regimen at our institution includes CsA, azathioprine, and steroids. Blood levels of CsA (whole blood, TDx assay) are maintained between 250 and 350 ng/mL for 0 to 6 months, 200 to 300 ng/mL for 6 to 12 months, and around 200 ng/mL beyond 12 months following lung transplantation. Nephrotoxicity, hypertension, susceptibility to infections, and malignancy are some of the serious side effects of CsA that limit its therapeutic usefulness. Acute rejection is relatively common with this regimen, and about 60% of all lung transplant recipients are treated for an episode of acute rejection within the first 12 months after lung transplantation. Acute rejection is a probable risk factor for chronic rejection, and obliterative bronchiolitis develops in about 50% of the patients who survive 5 years. Treatment of chronic rejection continues to be a challenge in lung transplantation. CsA and tacrolimus seem to have equivalent results in lung transplantation, although a few patients may benefit from the use of tacrolimus.

Acute Disease↗

PubMed2001

VATS port site recurrence: a technique dependent problem.

OBJECTIVES: Video-assisted thoracic surgery (VATS) has become an accepted approach for the diagnosis and treatment of thoracic malignancies. Port site tumor recurrence is a reported complication of VATS. However, the true incidence of this problem is unknown. To try to determine the incidence of port site recurrence, we analyzed our experience with patients undergoing VATS wedge resection for malignancy. METHODS: Data were obtained from our prospective VATS database. The analysis was confined to patients undergoing VATS wedge resection for malignancy, excluding those having a pleural biopsy only. Parameters analyzed included demographic factors, surgical technique, and port site recurrences identified by physical examination, CT scan, or both. RESULTS: From 1992 to 1996, 410 patients (182 men, 228 women; median age = 61 years) underwent a VATS wedge resection for malignancy. The procedure was performed for diagnosis or staging in 90% of cases. Access incisions plus port sites were used in 97 (24%) patients; port sites only were used in 313 (76%) patients. Conversion to thoracotomy was necessary in 102 patients (25%) either for definitive resection (58 patients) or because VATS was not technically adequate (44 patients). Specimens were retrieved via access incisions or port sites with or without a specimen bag. The operative mortality was 0.25%. With long-term follow-up (median = 25 months) available for 374 patients (91%), only one port site recurrence was identified (0.26%). CONCLUSION: Our experience confirms the safety of VATS wedge resection in cancer patients. The incidence of port site tumor recurrence is low when oncologic principles are respected. In our institution, these principles include performing VATS wedge resection only for lesions that can be widely removed; converting to thoracotomy for definitive or extensive cancer operation; and using meticulous technique for the extraction of specimens from the pleural space.

Adult↗

PubMed1999

The clinical course of lung carcinoma in patients with chronic lymphocytic leukemia.

BACKGROUND: Although patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary malignancies, including lung carcinoma, there is virtually no information about their clinical outcomes. To evaluate this, the authors reviewed their 20-year institutional experience with CLL patients who also had lung carcinoma. METHODS: The records of patients with diagnoses of both CLL and lung carcinoma seen between January 1977 and July 1998 were reviewed. The data collected included patient demographics, the tumor histology and stage, the type of treatment for both CLL and lung carcinoma, the presence of a third malignancy, the disease status at last follow-up, and the first site of relapse. Survival was calculated by the Kaplan-Meier method. RESULTS: From January 1977 to July 1998, 1329 patients with CLL were seen at Memorial Sloan-Kettering Cancer Center. Twenty-six (1.9%) also had lung carcinoma (19 males and 7 females). The median age of patients at the time CLL was diagnosed was 61 years, and for patients with lung carcinoma it was 68 years. Twenty-two patients (85%) were current or former smokers. Histologically, the lung carcinomas included 6 squamous cell carcinomas, 19 nonsquamous carcinomas, and 1 small cell carcinoma. Ten patients (38%) had a third malignancy; these malignancies included melanoma, basal cell carcinoma, laryngeal carcinoma, and colon carcinoma. Thirteen patients underwent surgical resection and 13 were treated nonsurgically for lung carcinoma. A poor performance status precluded surgery for 3 patients with Stage I tumors and limited chemotherapy for all patients with advanced disease. The median survival following the diagnosis of lung carcinoma for patients treated surgically was 25 months, and for those treated nonsurgically it was 6 months. CONCLUSIONS: Approximately 2% of patients with CLL develop lung carcinoma. In this study, 85% of the patients were smokers. These patients had a high risk of a third primary malignancy. Lung carcinoma was diagnosed a decade after CLL. Patients who develop both diseases die of lung carcinoma and not CLL or other solid tumors. CLL and poor performance status limit treatment, particularly for patients with unresectable lung carcinoma.

Adenocarcinoma↗

PubMed1994

Analysis of binding of monoclonal antibody to a malarial peptide by surface plasmon resonance biosensor and integrated rate equations.

Using biosensor technology and integrated rate equations, we have developed procedures to determine the kinetic parameters and equilibrium affinity constant of Ag-Ab interactions. The Ag used in these studies was a peptide that represents the major B cell epitope of the circumsporozoite protein of Plasmodium falciparum, a promising malaria vaccine candidate Ag. Measurements of association and dissociation rate constants of this peptide with the mAb 2A10 were determined by fitting integrated rate equations to binding data obtained with a BIAcore surface plasmon-resonance biosensor. We examined whether accurate estimates of initial velocity and final equilibrium levels of binding of Ab to peptides can be obtained using these methods, and whether kinetic rates and equilibrium constants obtained with systematic variation of the experimental parameters conform to a simple bimolecular model of binding. We found that initial velocity was approximately first order with respect to Ab concentration. When we used a series of four sensor cells with different peptides loads, however, we found that the initial velocity of binding appeared to be nearly independent of peptide concentration. Equilibrium analyses yielded dissociation constants of approximately 3 x 10(-7) M. Integrated rate treatment of biosensor data supports a critical examination of the assumptions on which the binding models are based and suggests a need to refine such models. Nevertheless, it provides a powerful quantitative tool for assessing the Ag-Ab binding reaction.

Amino Acid Sequence↗

PubMed1990

Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.

Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.

Antibody Specificity↗