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Biomedical subjects

S P Chawla

Publications and source records attributed to S P Chawla.

At least 19 recordsLinked to original sources
PubMed2003

Functional relevance of antiemetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant.

Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index-Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). Cisplatin-treated patients in a double-blind randomised trial received either aprepitant+dexamethasone+ondansetron on day 1 and aprepitant+dexamethasone on days 2-5 or standard antiemetic therapy (dexamethasone and ondansetron on day 1 and dexamethasone on days 2-5). Emetic events, nausea ratings and rescue medications were recorded in a 5-day diary and the FLIE was completed on day 6. Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients' daily lives.

Adolescent↗
PubMed2003

Effect of gamma irradiation on the survival of pathogens in kwamegi, a traditional Korean semidried seafood.

Kwamegi (semidried raw Pacific saury) is traditional seafood available in Korea. It has water activity in the range of 0.90 to 0.95. Spoilage and the growth of most pathogenic bacteria is retarded because of low water activity, low temperature, and packaging. However, it is contaminated with bacteria of public health significance and poses a hazard to the consumer because it is consumed raw without any cooking. The effectiveness of these hurdles in preventing the growth of Staphylococcus aureus, Bacillus cereus, Salmonella Typhimurium, and Escherichia coli and the efficacy of irradiation treatment in eliminating these bacteria from kwamegi using inoculated pack studies was examined. Radiation sensitivity of S. aureus, B. cereus, Salmonella Typhimurium, and E. coli in kwamegi was investigated. D10-values of these organisms in kwamegi were 590 +/- 13.6, 640 +/- 14.9, 560 +/- 45.4, and 550 +/- 8.6 Gy, respectively. The growth of all four test organisms inoculated into these foods during 4 weeks of storage at an ambient winter temperature (ranging from -5 degrees C to +5 degrees C) was recorded. All four pathogens (inoculated at 10(6) CFU/g) were eliminated by irradiation at 4 kGy. These studies unequivocally demonstrate that irradiation, with a combination of low water activity and low temperature, results in microbiologically safe kwamegi.

Animals↗
PubMed2002

Shelf-stable and safe intermediate-moisture meat products using hurdle technology.

A number of ready-to-use shelf-stable intermediate-moisture (IM) spiced mutton and spiced chicken products were developed with a combination of hurdles (reduced moisture, vacuum packing, and irradiation). The water activity of the products was reduced to about 0.80 either by grilling or by hot-air drying. These IM products were vacuum packed and subjected to gamma radiation processing at 0 to 10 kGy. Microbiological analyses revealed a radiation dose-dependent reduction in total viable counts and in numbers of Staphylococcus species. IM meat products that did not undergo radiation treatment showed visible mold growth within 2 months. The products subjected to irradiation at 10 kGy showed an absence of viable microorganisms and also retained high sensory acceptability for up to 9 months at ambient temperatures.

Animals↗
PubMed2001

Systemic irinotecan or regional floxuridine chemotherapy prolongs survival after hepatic cryosurgery in patients with metastatic colon cancer refractory to 5-fluorouracil.

Most colorectal cancers metastatic to the liver are resistant to chemotherapy and are not amenable to surgical resection. This study evaluated our 6-year experience (July 1992-July 1998) in treating patients with unresectable hepatic colorectal metastases refractory to systemic 5-fluorouracil (5-FU). One hundred fifty-three patients underwent cryosurgical ablation (CSA) of 5-FU-resistant hepatic metastases. The patients then received either hepatic arterial floxuridine (FUDR), systemic CPT-11, or no postoperative adjuvant chemotherapy. Number, size, and location of hepatic metastases, carcinoembryonic antigen (CEA) levels, and type of postoperative treatment were analyzed. One to 15 lesions were frozen (median number, 3; median size, 6 cm), for a total of 73 synchronous and 80 metachronous lesions. Overall median survival was 28.4 months from the date of diagnosis of liver metastases and 16.1 months from the time of CSA. After cryosurgery alone, median survival was 13 months, which was significantly shorter than the post-CSA survival of 23.6 months with adjuvant CPT-11 and 21.2 months with hepatic FUDR (P = 0.007). Predictors of survival included preoperative CEA, postoperative reduction in CEA, and adjuvant chemotherapy (P < 0.05). Neither size, number of lesions, nor tumor location impacted survival. At a median follow-up of 13 months, 67% of patients have recurred (35% hepatic, 16% extrahepatic, and 49% both). Twenty percent of the recurrences were in the lobe of the CSA site. The 25 patients who underwent a second CSA had a median survival of 28.4 months from CSA and 40 months from the date of diagnosis of liver metastases. These data indicate that CSA offers an effective alternative for unresectable patients resistant to 5-FU. Systemic CPT-11 or regional FUDR may further prolong survival after CSA.

Antimetabolites, Antineoplastic↗
PubMed1999

Cryosurgical ablation of soft tissue sarcomas: a phase I trial of feasibility and safety.

BACKGROUND: Cryosurgery is a therapeutic method of treating neoplastic tissue by freezing in situ to achieve devitalization. Cell death results from exposure to severe cold (below -40 degrees C for at least 1 minute) as well as from the process of freezing and thawing, which disrupts cellular integrity. Modern cryosurgical technique involves insertion of hollow probes into the tumor, through which circulating liquid nitrogen and gaseous nitrogen can achieve tissue and tumor freezing and thawing for tumor control. Cryoablation is now a recognized approach to the treatment of various malignant tumors, and it is generally well tolerated. This method has been used only sporadically to date in the treatment of patients with soft tissue sarcomas. METHODS: The purpose of this study was to assess the feasibility and safety of cryosurgical ablation of soft tissue sarcomas utilizing a cryoprobe system. Twelve patients with soft tissue tumors of the extremity were included in this Institutional Review Board-approved protocol. Cryoablation was performed by inserting cryoprobes into the tumors, through which liquid nitrogen and gaseous nitrogen were pumped to achieve two freeze/thaw cycles. The entire process was monitored with intraoperative ultrasonography. All patients had subsequent resection of the residual tumor. Patients were monitored clinically and metabolically for toxicity. RESULTS: Cryoablation was successfully performed on all 12 patients. Complications included peripheral nerve palsy (in 3 patients) and serous wound drainage (in 3 patients). There were no cases of wound infection, deep venous thrombosis, pulmonary embolism, wound dehiscence, skin slough, or metabolic abnormalities. All 3 cases of peripheral nerve palsy showed signs of recovery, 2 within 1 week and 1 within 4 months. CONCLUSIONS: Cryosurgical ablation of soft tissue sarcomas is technically safe and feasible. This method can be used in conjunction with other modalities in the treatment of patients with these tumors. The complications associated with cryoablation of sarcomas are minor or transient, and the procedure is well tolerated by patients. The role of cryosurgery in the management of soft tissue sarcomas needs to be elucidated as more data regarding its safety and effectiveness become available.

Adult↗
PubMed1992

Preoperative chemotherapy for osteosarcoma with intravenous adriamycin and intra-arterial cis-platinum.

Ninety-seven patients with primary osteosarcoma of the extremities, all age 16 or older, were treated with adriamycin, 90 mg/m2, continuous i.v. infusion over 96 h, followed by cis-platinum, 120-160 mg/m2 by intra-arterial infusion. The first 37 patients, treated from 1979-1982, had a 59% complete response rate and a 54% 5-year continuous disease free survival (CDFS). Patients with complete response had an 85% 5-year CDFS compared with 13% for patients with partial and poor response. Patients treated between 1983-1988 with an intensified regimen have a 68% complete response rate and a 69% 3-year CDFS. Those who did not achieve complete remission were switched to an alternating chemotherapy program emphasizing the use of high-dose methotrexate. Limb salvage has been accomplished in 59% of patients in the first group and 80% in patients of the second group. Preoperative chemotherapy allows informed decisions to be made in postoperative management which can influence overall cure rates. Long-term follow-up is essential before final interpretation of the data.

Bone Neoplasms↗
PubMed1992

Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level.

PURPOSE: The purpose of this study was to optimize the dose, schedule, and timing of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administration that would best abrogate myelosuppression in patients with sarcoma. PATIENTS AND METHODS: Sarcoma patients who had experienced severe myelosuppression after chemotherapy with Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dacarbazine ([CyADIC], cycle 1) were eligible. GM-CSF was administered during a 14-day period until 1 week before cycle 2 of CyADIC and was resumed 2 days after cycle 2 completion. The schedule subsequently was modified to allow the earlier administration of GM-CSF in which CyADIC was compressed from 5 days to 3 days, and GM-CSF was administered immediately after the discontinuation of CyADIC in cycle 2. To understand better the impact of GM-CSF on bone marrow stem cells, the proliferative status of bone marrow progenitors was examined during treatment. To evaluate the effects of GM-CSF on effector cells, select functions of mature myeloid cells were also examined. RESULTS: In the seven patients who were treated on the initial schedule, GM-CSF enhanced the rate of neutrophil recovery; however, severe neutropenia was not abrogated, By using the modified schedule in 17 patients, GM-CSF significantly reduced both the degree and the duration of neutropenia and myeloid (neutrophils, eosinophils, and monocytes) leukopenia. The mean neutrophil and mature myeloid nadir counts were 100/mm3 and 280/mm3 in cycle 1 and 290/mm3 and 1,540/mm3 in cycle 2 (P less than .01 and P less than .001). The duration of severe neutropenia (neutrophil count less than 500/mm3) and myeloid leukopenia (myeloid leukocyte count less than 1,000/mm3) were reduced from 6.2 and 6.8 days in cycle 1 to 2.8 and 1.4 days in cycle 2 (P less than .001). While 16 of 17 patients experienced severe myeloid leukopenia (less than 500/mm3) in cycle 1, only two of 17 experienced severe myeloid leukopenia in cycle 2 (P less than .001). Overall, severe neutropenia was abrogated in seven patients, which made them eligible for dose-escalation of Adriamycin. The fraction of cycling progenitors increased threefold on GM-CSF and decreased dramatically below the baseline within 1 day of GM-CSF discontinuation. CONCLUSIONS: The modified schedule improved the beneficial effects of GM-CSF by enhancing myeloprotection and permitting dose-intensification of chemotherapy. The increased myeloid mass and quiescent progenitors at the initiation of chemotherapy suggest that GM-CSF might allow further chemotherapy dose-rate intensification by shortening the interval between courses.

Adolescent↗
PubMed1989

Recovery of sperm production after chemotherapy for osteosarcoma.

Because treatment with surgery and combination chemotherapy produces a high cure rate in young men with osteosarcoma, their subsequent reproductive function is an important concern. Semen analyses of osteosarcoma patients, therefore, were performed before, during, and after treatment with the PADIC regimen consisting of cisplatin, Adriamycin (doxorubicin), and dacarbazine or, in some cases, the PADIC regimen plus additional drugs. Results showed that semen volume was not affected and that sperm motility was reduced only during treatment. Although nearly all patients were rendered azoospermic during treatment, sperm production resumed in 30 of 32 patients examined at least 2 years after treatment. Analysis with correction for censored data indicates that, in 78% of treated men, sperm counts will return to more than 10 million/ml. The percentage of men whose sperm counts recovered to normal was lower for those receiving cisplatin dosages greater than or equal to 600 mg/m2; no trends were observed with Adriamycin and dacarbazine dosages. The inclusion of additional drugs such as methotrexate, bleomycin, dactinomycin, or cyclophosphamide (less than 4 g/m2) did not significantly affect the recovery of spermatogenesis. We conclude that the risk of long-term infertility from treatment with the PADIC regimen is low.

Adolescent↗
PubMed1989

Advanced basal cell carcinoma and successful treatment with chemotherapy.

The patient presented in this report has a large basal cell carcinoma on the wrist and thigh. The lesion on the wrist was nonresectable without amputation. The patient showed an impressive response to chemotherapy with systemic cyclophosphamide, adriamycin, and intra-arterial cisplatin. The tumor could be excised by a simple excision on both sites and showed no residual tumor on the hand and only a microscopic focus on the thigh. The patient continues to be free of disease 3 years after the initiation of the therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

A comparative study of doxorubicin and epirubicin in patients with metastatic breast cancer.

Seventy-seven patients with progressive metastatic breast cancer refractory to prior therapy participated in a prospective randomized trial designed to compare the efficacy and toxicity of doxorubicin and epirubicin administered as single agents. In arm 1, 60 mg/m2 of doxorubicin and, in arm 2, 90 mg/m2 of epirubicin were administered by 48-h continuous i.v. infusion every 3 weeks. In arm 3, 90 mg/m2 of epirubicin was administered by bolus every 3 weeks. Patients in the three groups had similar characteristics, except that in arm 3 more patients were premenopausal, had more extensive disease, and fewer patients had been exposed to doxorubicin. Objective remission rates were 29, 26, and 13%, respectively for the three arms. Median response durations ranged from 4-6 months. No significant differences occurred in response rate, remission duration, or survival among patients in the three arms. The incidence of gastrointestinal toxicity and alopecia was evenly distributed. Hematologic toxicity was more severe in arms 2 and 3, and there was a higher incidence of infectious complications in arms 2 and 3 compared to arm 1 (p = 0.05). Two episodes of congestive heart failure occurred in arm 1, one in arm 2, and three in arm 3. Although the total cumulative anthracycline dosage was highest in the arm 2 group, they had the lowest incidence of cardiac toxicity. Epirubicin by bolus and doxorubicin administered by continuous infusion have similar potential for cardiac toxicity. Epirubicin administered by continuous infusion appears less cardiotoxic than doxorubicin by either method of administration or epirubicin given by bolus. Epirubicin appears equally active and less cardiotoxic than the parent compound doxorubicin in patients with metastatic breast cancer.

Adult↗
PubMed1989

Osteosarcoma: angiographic assessment of response to preoperative chemotherapy.

Adjuvant chemotherapy prolongs the survival of patients with high-grade osteosarcoma. Preoperative chemotherapy allows identification of effective agents for adjuvant chemotherapy based on response of the primary tumor. Preoperative determination of tumor response has therapeutic implications, and angiography offers a less subjective means of assessing it than do conventional radiography or computed tomography. Changes in tumor vascularity, as seen angiographically, after two courses and at the time of the last of several courses of preoperative chemotherapy were correlated with histologic tumor necrosis of resected specimens in 81 patients. Angiographically, 40% of the histologic responders and 91% of the nonresponders were identified after two courses of preoperative chemotherapy. After a median of four courses of chemotherapy, 91% of the responders but only 50% of the nonresponders were identified angiographically. Angiographic assessment of tumor vascularity, although not of absolute value, offers a useful guideline for determining the preoperative chemotherapy strategy.

Adult↗
PubMed1988

Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors.

Thirty-seven cases of uterine leiomyosarcoma are presented, along with nine cases of leiomyoma variants from which they were distinguished. All patients were followed for a minimum of 10 years. In cases with nuclear pleomorphism, leiomyosarcoma was diagnosed when there were five or more mitotic figures in ten consecutive high-power (X400) fields in the most active area of the tumor, and also when there were fewer mitotic figures but extensive tumor necrosis (there was only one leiomyosarcoma without nuclear pleomorphism, and it had more than 20 mitotic figures in ten high-power fields). Tumor size was the major prognostic factor in the leiomyosarcoma group; five of eight patients with neoplasms measuring less than 5 cm in maximum dimension survived, whereas no patient with a larger tumor did so. Other pathologic and clinical variables, including mitotic rate, tumor necrosis, degree of nuclear pleomorphism, vascular invasion, and patient age, had no significant relationship to survival or tumor behavior in leiomyosarcoma when tumor size was taken into account. The nine cases of leiomyoma variants consisted of three atypical leiomyomas (which had nuclear pleomorphism, one or no mitotic figures per ten high-power fields, and no necrosis), two plexiform leiomyomas, two cases of peritoneal leiomyomatosis, one palisaded leiomyoma, and one case of intravenous leiomyomatosis; all of these patients were tumor-free on follow-up.

Adult↗
PubMed1988

Phase I study of weekly-administered iproplatin [cis-dichloro-trans-dihydroxy-bis-isopropylamine platin (chip, JM9)].

Iproplatin [cis-dichlor-trans-dihydroxy-bis-isopropylamine platinum (CHIP, JM9)] is a new antineoplastic platinum analogue with an octahedral conformation. It has more water solubility than does cisplatin and was found to have less neurotoxicity and nephrotoxicity in experimental animals than cisplatin. Like cisplatin, it has been demonstrated to have a broad spectrum of activity in experimental tumor systems. A phase I study of iproplatin was conducted in 28 patients (12 with melanoma, 8 with sarcoma, 6 with breast cancer, and 2 with colon cancer). All patients had failed prior chemotherapy. Four consecutive doses of iproplatin were administered at weekly intervals followed by a rest period of two weeks for hematologic recovery (one course). One hundred forty-two weekly doses were administered with all patients except three receiving at least one full course. The weekly starting dose of 40 mg/m2 was increased to 120 mg/m2 given over 30 minutes without hydration. Myelosuppression predominantly thrombocytopenia, was the dose-limiting toxicity at weekly doses of greater than or equal to 95 mg/m2 per course. With iproplatin doses 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median granulocyte counts were 2.6 x 10(3)/mm3, 2.2 x 10(3)/mm3, and 1.8 x 10(3)/mm3, respectively. Similarly, at iproplatin doses of 75 mg/m2, 95 mg/m2, and 120 mg/m2, the lowest median platelet counts were 144 x 10(3)/mm3, 99 x 10(3)/mm3, and 31 x 10(3)/mm3, respectively. Mild to moderate nausea and vomiting were observed in the majority of patients. No significant neurotoxicity, nephrotoxicity, or ototoxicity was observed. Objective tumor regression was not observed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1987

Clinical evaluation of recombinant interferon alfa-2a (Roferon-A) in metastatic melanoma using two different schedules .

Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.

Adolescent↗
PubMed1987

Osteosarcoma chemotherapy effect: a prognostic factor.

Chemotherapy has become a routine part of the treatment of osteosarcoma. However, the precise role of preoperative chemotherapy remains in question. Between 1979 and 1982, a group of 40 patients were treated by multimodality therapy consisting of preoperative chemotherapy (intra-arterial cis-platinum and systemic adriamycin), surgery, and postoperative chemotherapy. Survival in this group is 64%, while continuous disease-free survival is 58%. Although age, sex, tumor size, site, and classification were found to be prognostic factors, histologic evidence of response to preoperative chemotherapy, measured as percent tumor necrosis, was found to be the most significant prognostic factor. When continuous disease-free survival was calculated as a function of tumor necrosis it was 91% in patients with greater than or equal to 90% tumor necrosis, while it was 14% in patients with less than 90% tumor necrosis. At initial presentation, 7% of patients were judged limb-salvage candidates. But due to the local effects of preoperative chemotherapy, 60% ultimately underwent limb-salvage surgery. Preoperative arteriograms were a reliable means of monitoring response to chemotherapy and served as an indicator of residual viable tumor. Using arteriogram directed planes of section, postchemotherapy, specimens were "mapped" and analyzed for chemotherapy effect. When present, residual viable tumor was preferentially found at the interface of tumor and normal anatomic structures; "sanctuary sites." It is necessary that standard methods for analyzing postchemotherapy specimens be developed; a technique is described.

Bone Neoplasms↗
PubMed1986

Chondrosarcoma with additional mesenchymal component (dedifferentiated chondrosarcoma). I. A clinicopathologic study of 26 cases.

During a 37-year period, 26 patients were seen who had chondrosarcoma with additional mesenchymal components ("dedifferentiated low-grade chondrosarcoma"). Sixteen were men and 10 were women aged 30 to 85 years (median, 61 years). The tumors' chondroid areas were of borderline or low-grade malignancy. The additional mesenchymal component was histologically classified as malignant fibrous histiocytoma (16), rhabdomyosarcoma (4), low-grade fibrosarcoma (3), osteosarcoma (2), and undifferentiated sarcoma (1). Preferred locations were pelvis (10) and femur (8). Symptoms had been present for 1 year or less in most cases. Pain was the most common symptom. In 15 of 26, major amputation was the primary treatment. Twelve patients received chemotherapy, usually after developing metastatic disease, but only one achieved a partial response. Median disease-free interval after diagnosis was 4 months, median survival was 6 months, and 19 patients died within 1 year. Of 4 who survived longer than 18 months, 3 presented with a low-grade fibrosarcoma. Survival and development of metastasis appeared unrelated to cell type, initial treatment, or chemotherapy, except when the tumor's initial nonchondroid component was low-grade fibrosarcoma.

Adult↗
PubMed1986

Phase II studies of homoharringtonine in patients with advanced malignant melanoma; sarcoma; and head and neck, breast, and colorectal carcinomas.

Five phase II trials of the antitumor agent homoharringtonine were conducted in 80 patients who had advanced solid tumors. The five categories of solid tumors included malignant melanoma; sarcoma; and head and neck, breast, and colorectal carcinomas. The starting dose of homoharringtonine was 3.0-4.0 mg/m2 by short iv infusion daily X 5 days every 21 days. Seventy-eight of 80 patients had had prior chemotherapy and 49 had had prior radiation therapy. Among the 74 evaluable patients in the five tumor categories, there were no complete or partial remissions. Homoharringtonine was generally well-tolerated. Nausea and vomiting, diarrhea, and fever and chills were the most common side effects. Serious reversible cardiovascular toxicity, which occurred in three patients, included symptomatic hypotension in two and short runs of ventricular tachycardia in one. The investigations thus conclude that homoharringtonine given by intermittent schedule is an inactive drug against these solid tumors previously exposed to chemotherapy.

Adolescent↗