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Biomedical subjects

P R Sarma

Publications and source records attributed to P R Sarma.

16 recordsLinked to original sources
PubMed1994

Crystallization and preliminary X-ray diffraction studies on a trypsin/chymotrypsin double-headed inhibitor from horse gram.

The Bowman-Birk family of proteinase inhibitors from seeds of leguminous plants usually have a molecular mass of 8000 to 10,000 Da. Horse gram (Dolichos bifloros or Macrotyloma uniflorum) seeds contain an unusual Bowman-Birk inhibitor of molecular mass 15,500 Da active against both trypsin and chymotrypsin. In order to elucidate its three-dimensional structure, its evolutionary relationship with the more usual Bowman-Birk inhibitors and to study the structure-function properties, this inhibitor has been purified and crystallized. The purified protein crystallizes easily under a variety of conditions in different crystal forms. Crystals obtained by precipitating the protein (3 to 5 mg/ml in 50mM Tris.HCl (pH 8.0)) with 5% ammonium sulphate and 2 to 3% PEG 4000 appear to be suitable for structure determination by X-ray diffraction. The crystals belong to cubic space group P2(1)3 (a = 110.81 A) and diffract X-rays to beyond 3.0 A resolution.

Chymotrypsin↗
PubMed1993

Preoperative irradiation and fluorouracil chemotherapy for locally advanced rectosigmoid carcinoma: phase I-II study.

From June 1988 to July 1991, 20 patients with locally advanced rectal or rectosigmoid cancer were treated prospectively with a strategy of combining preoperative irradiation and fluorouracil chemotherapy before surgical resection. The preoperative radiation dose was 5,000 cGy, and fluorouracil chemotherapy was administered on the first and last 3 days of irradiation in an intravenous bolus dose of 500 mg/m2. In a median follow-up of 25 months, the local regional failure rate was 10%. The 3-year actuarial overall survival and disease-free survival were 92% and 82%, respectively. Twenty percent of the surgical specimens showed no residual tumor, and only 10% showed positive lymph nodes. Significant leukopenia occurred in 10% of patients. Preoperative irradiation and fluorouracil chemotherapy increased surgical downstaging and improved local regional control. The overall toxicity was acceptable. The results of this particular multimodality approach was encouraging and warrant further investigation in phase III trials.

Adult↗
PubMed1992

Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia.

PURPOSE: This multicenter, double-blind, randomized trial was performed to determine the efficacy and safety of pamidronate disodium (APD) in comparison to etidronate disodium (EHDP) in the treatment of cancer-related hypercalcemia. PATIENTS AND METHODS: Sixty-five male and female adult patients with cancer and corrected calcium levels of greater than or equal to 12.0 mg/dL after 24 hours of hydration were randomized to receive either 60 mg APD given as a single 24-hour infusion or 7.5 mg/kg EHDP given as a 2-hour infusion daily for 3 days. RESULTS: APD normalized corrected calcium levels in 70% (21 of 30) of patients, whereas EHDP did so in 41% (14 of 34) of patients (P = .026). The mean corrected serum calcium level decreased from 14.6 to 10.5 mg/dL in the APD-treated group and from 13.8 to 11.6 mg/dL in the EHDP-treated group within the first week of treatment. There was no difference in response to APD in patients without versus those with bone metastases (78% v 67%). Both drugs were well tolerated. CONCLUSION: This study demonstrated that a single 60-mg infusion of APD is safe and more effective than EHDP given at the dose of 7.5 mg/kg for 3 days in the treatment of cancer-related hypercalcemia.

Adult↗
PubMed1990

Randomized comparison of two combination regimens versus minimal chemotherapy in nonsmall-cell lung cancer: a Southeastern Cancer Study Group Trial.

Patients with advanced nonsmall-cell lung cancer (NSCLC), good performance status, and no prior chemotherapy were randomized to receive one of three regimens: intravenous vindesine (V) 3 mg/m2 every 2 weeks; V 3 mg/m2 weekly for 5 weeks, followed by a dose every 2 weeks plus mitomycin (VM) 20 mg/m2 day 1 and then 15 mg/m2 every 6 weeks; or V at the more intensive dose rate plus cisplatin (VC) 120 mg/m2 with forced diuresis on days 1 and 29 and then every 6 weeks. A total of 435 patients were enrolled in the trial, with 410 (94%) assessable for prognostic characteristics and survival. Among the 375 patients assessable for response, only 58 (15%) achieved objective response. Single-agent V every 2 weeks was inactive (response rate less than 1%), effectively acting as a no-treatment arm. Among assessable patients receiving VM, 33 (27%) responded; among patients receiving VC, 24 (19%) responded. There was no statistically significant survival difference among the treatment arms, with median survival among those treated with V 14.8 weeks, VM 20.4 weeks, and VC 24.7 weeks; VC achieved borderline significance (P = .06) compared with V. In a prognostic factor analysis, treatment was not a significant factor (P = .447) for survival. Thus, in this large multicenter trial, neither a high-dose cisplatin combination nor a noncisplatin regimen (VM) with a comparable response rate had a significant survival advantage over minimal chemotherapy. New approaches are needed in advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Serum alpha-1 proteinase inhibitor in advanced cancer: mass variants and functionally inert forms.

In 1984, we reported that while immunoreactive levels of serum alpha-1 proteinase inhibitor (API) increased significantly in nine patients with advanced solid tumors, the functional activity of the inhibitor, as measured by the serum trypsin inhibitory capacity, did not increase proportionately. This suggested that a portion of the circulating API was functionally inert. We have now assayed immunoreactive titers and trypsin inhibitory capacity of serum API of 49 patients with advanced carcinomas and 27 healthy controls. Immunoreactive levels of API (expressed as percentage of normal pooled serum which was taken as 100%) in cancer subjects were significantly elevated as compared to normals (mean +/- SE: 233 +/- 9.0% versus 102 +/- 2.0%, P less than 0.05). Although the trypsin inhibitory capacity of the cancer group (16.0 +/- 0.9 units/ml) was significantly elevated (P less than 0.05) as compared to normals (9.9 +/- 0.1 units/ml), this increase was less than that in the immunoreactive titer of API, suggesting the existence of functionally inert API in serum. The fraction of API which was functionally active in this group of cancer patients was 71.0 +/- 3.0% which was significantly less than the normal 98.0 +/- 2.0% (P less than 0.05). In 12 patients followed serially, both immunoreactive levels of API and the trypsin inhibitory capacity increased significantly at the time of clinical progression of disease. There was a significant correlation between increasing absolute granulocyte count and increasing trypsin inhibitory capacity (correlation coefficient 0.66; P less than 0.001). Neither disease progression nor increasing granulocyte count, however, was associated with increasing proportion of functionally inactive API. The inactive form of API had the same molecular weight as the native molecule as shown by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis of cancer sera. Therefore, the inactive form was not due to a complex between API and a tumor-derived protease or to proteolytic fragmentation of the native API. Elastase inhibitory capacity of cancer sera with subactive API was essentially identical with trypsin inhibitory capacity indicating that the active site methionine was not oxidized in the inert API. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis showed that both normal and cancer serum API existed as two mass variants, at Mr 58,000 and 56,000. Both variants formed complexes with elastase and were functionally active.

Blood Proteins↗
PubMed1987

Pseudopseudotumor cerebri: meningeal carcinomatosis presenting as benign intracranial hypertension.

We have described a 63-year-old man, taking diethylstilbestrol for adenocarcinoma of the prostate, who had papilledema. Lumbar puncture revealed intracranial hypertension without pleiocytosis. CT scan was normal, consistent with the diagnosis of pseudotumor cerebri. At craniotomy for placement of a ventriculoperitoneal shunt, the dura was found to be infiltrated with adenocarcinoma. In patients with known malignancy and elevated intracranial pressure, lumbar puncture and CT scan alone are not enough to rule out meningeal carcinomatosis; repeated lumbar puncture or cervical cisternal puncture may be necessary to document malignant cytology.

Adenocarcinoma↗
PubMed1986

Phase II evaluation of cisplatin, bleomycin, and vindesine in advanced squamous cell carcinoma of the esophagus: a Southeastern Cancer Study Group Trial.

Adults with advanced, measurable, squamous cell carcinoma of the esophagus were treated with a combination of cisplatin, bleomycin, and vindesine. Of 27 evaluable patients, seven (29%) had partial response, all occurring within the first two cycles of therapy. Of 13 patients receiving more than two cycles, only five completed the five planned cycles of therapy and did not progress while receiving the additional three cycles. Granulocytopenia was the major toxic effect observed, with 52% of the patients having neutrophil counts less than 1000/mm3. Findings suspicious for bleomycin pulmonary toxicity were observed in two evaluable patients and bleomycin toxicity was pathologically confirmed in one ineligible patient. Based on the results of this study, this regimen cannot be recommended for routine use in patients with advanced esophageal cancer. The search for more effective and less toxic regimens should continue.

Aged↗
PubMed1986

Biclonal gammopathy (IgG kappa and IgG lambda) in a patient with non-Hodgkin's lymphoma.

We report a case of non-Hodgkin's malignant lymphoma with biclonal gammopathy (IgG kappa and IgG lambda) involving both serum and urine. Detailed immunologic studies of the tumor disclosed two morphologically indistinguishable clones of cells that were responsible for the production of the two monoclonal immunoglobulins. This, to our knowledge, is the first documented case of a biclonal gammopathy involving a single heavy-chain class with both kappa and lambda light chains in a non-Hodgkin's lymphoma. Lesions resembling lymphomas must not be assumed to be inflammatory simply because the cells express both kappa and lambda antigens.

Aged↗
PubMed1979

"CAMP" combination chemotherapy for unresectable non-oat cell bronchogenic carcinoma.

Experience with camp chemotherapy of 84 unresectable non-oat cell lung cancer patients is described. Fourteen (27%) of 51 patients with measurable lesions responded (3 CR, 11 PR) for a median response duration of 5 months with a range of 1 to 19+ months. Median survival of responders was 370 days, but response was not independent of performance status. Survival of patients without measurable lesions was less favorable than that of even nonresponders, suggesting prediction of response to CAMP by site of metastasis. Preliminary results of a randomized prospective trial of the CAMP combination versus CCNU as a single agent for patients with good performance status fail to show a difference in survival.

Antineoplastic Agents↗
PubMed1978

Approach to the management of pleural effusion in malignancy.

The diagnostic and therapeutic approaches to malignant pleural effusions are reviewed, and data on the retrospective study of 37 patients are presented with respect to diagnosis and management. All patients with stable effusions should be managed with systemic therapy for the primary tumor when an effective agent is available. When it becomes necessary to use local therapeutic measures, thoracostomy tube drainage with local instillation of tetracycline is recommended.

Antineoplastic Agents↗
PubMed1977

Acute renal failure after low-dose irradiation. A complication of chronic lymphocytic leukemia.

A middle-aged woman received low-dose irradiation for treatment of chronic lymphocytic leukemia: 1,000 rads to the spleen in four sessions over four days and 400 rads to each abdominal quadrant in eight sessions over eight days. Three days after the last irradiation session, acute hyperuricemic renal failure developed and conservative treatment was begun, with use of hydration, forced diuresis, alkalization, and short-term peritoneal dialysis. Uric acid levels were carefully monitored. Renal function promptly returned to normal.

Acute Kidney Injury↗
PubMedDate not supplied

Oral exfoliative cytology in female reverse smokers having stomatitis nicotina.

1. The Karyopyknotic index of the palatal and lingual mucosa is increased in female reverse smokers when compared to non-smoking females. 2. The Karyopyknotic index of the buccal mucosa did not show any change in female reverse smokers when compared to non-smoking females. 3. The Karyopyknotic index did not show any change with age in the non-smoking females. 4. Very few cases show epithelial atypia in palatal smears from female reverse smokers having stomatitis nicotina.

Adolescent↗
PubMedDate not supplied

Nature of the tryptic/chymotryptic inhibitor from horsegram (Dolichos biflorus).

A protease inhibitor specific to trypsin and chymotrypsin was purified from horsegram (Dolichos biflorus) with the inhibition index 0.24 micrograms/micrograms for trypsin and 0.36 micrograms/micrograms for chymotrypsin. In SDS-PAGE, the inhibitor protein was seen as a single band with apparent molecular mass Mr = 15,500. However, on fast protein liquid chromatography (FPLC) or non-denaturating PAGE, the inhibitor resolved into four components revealing the existence of isoinhibitors. Data on amino acid analysis indicate that the isoinhibitors are closely related. The major amino acids in the inhibitor are half cystine (18.9 mole %), aspartic acid (12.7 mole %) and serine (14.3 mole %). The inhibitor was partially stable to 0.1% sodium dodecyl sulphate, 8M urea or 6M guanidine hydrochloride. The inhibitory activity was lost on reduction or carboxamidomethylation or acetylation. Modification of the arginine groups or CNBr cleavage of the protein did not result in significant loss of either tryptic or chymotryptic inhibitory activities. The isoinhibitors separated by FPLC reacted with polyclonal antibody raised in rabbits and had pI values ranging from 4.8-5.1. The horsegram inhibitor thus resembles other Bowman-Birk protease inhibitors.

Amino Acids↗
PubMedDate not supplied

Immediate versus postponed combination chemotherapy (CAMP) for unresectable non-small cell lung cancer: a randomized trial.

A randomized control trial was performed in good performance status patients with unresectable non-small cell lung cancer to test a strategy of early aggressive combination chemotherapy (CAMP [cyclophosphamide, doxorubicin, methotrexate, and procarbazine]) versus a strategy of delaying such treatment until clinical deterioration. Thirty-seven patients received immediate CAMP and 35 patients received initial low-dose single-agent CCNU (CAMP was postponed). Immediate CAMP therapy produced an objective response rate of 44% in patients with measurable lesions, and CCNU produced none. Median survival was 193 days for the immediate-CAMP group and 175 days for the postponed-CAMP group (P = 0.26). Measures of quality of life were made and no difference emerged between the two treatment strategies. This trial failed to show substantial benefit from immediate combination chemotherapy in minimally symptomatic patients with non-small cell lung cancer.

Antineoplastic Agents↗