Statistics and thermodynamics of luminescent radiation.
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Journal Article↗
Biomedical subjects
R Barakat
Publications and source records attributed to R Barakat.
Impact of laparotomy finding of significant intraabdominal adhesions on the surgically defined complete response rate to subsequent salvage intraperitoneal chemotherapy.
One possible explanation for the failure of the high concentrations of cytotoxic agents achieved following intraperitoneal (i.p.) drug delivery to produce a favorable response in patients with ovarian cancer is the inability of the drug-containing fluid to be adequately distributed throughout the peritoneal cavity, usually because of intraabdominal adhesion formation. To evaluate the influence of the severity of adhesions, observed at the time of laparotomy performed immediately preceding the initiation of i.p. therapy, on the ability to achieve a surgically defined complete response (S-CR), we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 salvage i.p. trials at the Memorial Sloan-Kettering Cancer Center. The S-CR rate in the 36 patients with limited adhesion formation observed upon entering the peritoneal cavity was 28%, compared to 35% in the 34 patients with extensive adhesions (P greater than 0.05). In 33 patients treated with a phase-2 cisplatin-based i.p. program, who had previously responded to systemic platinum, 47% (8/17) and 44% (7/16) of those with limited and extensive adhesions, respectively, achieved a S-CR (P greater than 0.05). We conclude that the presence of extensive adhesions observed within the peritoneal cavity at the time of a laparotomy performed immediately prior to the initiation of i.p. therapy does not have a negative impact on the potential to achieve an S-CR, assuming it is technically feasible to lyse all significant adhesions prior to the completion of the operative procedure.
Abdomen↗
Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer.
Eighteen previously treated patients with advanced ovarian cancer were entered into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days, repeated every 28 days) to determine the activity of this therapeutic strategy in organoplatinum-refractory disease. The treatment program was generally well tolerated, with mild neutropenia the most common side-effect encountered. One patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which lasted for 11 months. Three additional patients (17%), who failed to meet the criteria of a partial response, demonstrated objective evidence of antineoplastic activity. Chronic low-dose oral etoposide administration is associated with definite, although modest, activity in platinum-refractory ovarian cancer.
Carboplatin↗
Association between pretreatment CA-125 levels and surgically documented complete responses in patients with ovarian cancer treated with second-line intraperitoneal therapy.
Approximately 20%-40% of patients with small-volume residual ovarian cancer, following systemically administered platinum-based chemotherapy, will respond to a second-line intraperitoneal treatment regimen. In an effort to improve the selection criteria for patients being considered for this regional therapeutic approach, we retrospectively evaluated the influence of pretreatment CA-125 levels on the ability of a group of 70 patients with small-volume residual ovarian cancer (no tumor mass greater than 1 cm in diameter) to achieve a surgically defined complete response (S-CR) following treatment on one of three phase-2 intraperitoneal chemotherapy trials conducted at the Memorial Sloan-Kettering Cancer Center. Overall, 18/46 (39%) patients with normal pretreatment CA-125 levels (less than or equal to units/ml) achieved a S-CR, compared to only 4/24 patients (17%) with an elevated pretreatment value (chi 2 = 3.7, P greater than 0.5). Despite the lower S-CR rate in patients with elevated CA-125 levels, the duration of response and survival were similar in the two patient populations achieving a S-CR. Thus, we conclude that an elevated pretreatment CA-125 level in a patient with small-volume residual ovarian cancer should not be used by itself to disqualify an individual from consideration for a second-line intraperitoneal treatment regimen, although the finding suggests a reduced likelihood of achieving a S-CR with this therapeutic approach.
Antigens, Tumor-Associated, Carbohydrate↗
Salvage intraperitoneal therapy of small-volume residual ovarian cancer: impact of pretreatment finding of peritoneal carcinomatosis on the surgical complete response rate.
Second-line intraperitoneal (i.p.) therapy has been demonstrated to result in surgically defined complete responses (S-CR) in 25%-40% of patients with small-volume residual ovarian cancer (microscopic disease or largest tumor mass less than 1 cm in diameter). To evaluate the influence of the surgical finding of diffuse peritoneal carcinomatosis on the S-CR rate to salvage i.p. therapy in this patient population, we retrospectively reviewed the operative reports of 70 patients with small-volume residual ovarian cancer treated on one of three phase-2 second-line i.p. trials at the Memorial Sloan-Kettering Cancer Center. Of the 11 patients with diffuse carcinomatosis, none achieved a S-CR compared to a S-CR rate of 37% (22/59) in patients without this surgical finding (chi 2 = 6.0; P less than 0.025). However, of the 7 patients with diffuse carcinomatosis treated on a cisplatin-based i.p. program, the only 2 who had previously responded to systemic platinum also experienced a response (partial) to the i.p. cisplatin regimen. In conclusion, while the surgical finding of diffuse peritoneal carcinomatosis indicates a poor prognosis in patients with small-volume residual ovarian cancer for response to i.p. chemotherapy, patients in this clinical setting with prior evidence of platinum sensitivity may experience some benefit from an i.p. cisplatin-based treatment strategy.
Cisplatin↗
Random genetic drift and selection in a triallelic locus: a continuous diffusion model.
The Kolmogorov forward diffusion equation is used to examine the evolution of three alleles at one locus under viability selection and random genetic drift. Separation of variables and Chebyschev approximations are employed to solve this equation for long times. As an example, one artificial viability set is examined in detail; its general implications for the evolution at a triallelic locus are discussed.
Alleles↗
Phase 2 trial of intraperitoneal carboplatin and etoposide as salvage treatment of advanced epithelial ovarian cancer.
To evaluate the efficacy of intraperitoneal (IP) carboplatin-based therapy as salvage treatment of ovarian cancer, 46 patients with persistent or recurrent ovarian cancer following initial systemic chemotherapy were treated with a regimen of carboplatin (200-300 mg/m2) and etoposide (100 mg/m2) administered on a monthly schedule. A maximum of six courses of therapy was delivered, followed by a response laparotomy. The treatment program was well tolerated, except for bone marrow suppression, with one-quarter of patients developing platelet count depressions to < or = 50,000/mm3, and one-third experiencing hemoglobin levels of < or = 8 g/dl during treatment. Twelve (38%) of 32 patients evaluable for efficacy of the treatment program achieved a surgically documented response, including 8 (25%) complete responses. Of 25 patients whose largest tumor mass at the initiation of therapy measured < or = 0.5 cm, 11 (44%) responded, including 8 (32%) complete responses. We conclude that the IP administration of carboplatin can result in surgically documented responses when used in the salvage setting in patients with advanced ovarian cancer. The relative efficacy of carboplatin versus cisplatin when administered by the IP route to patients with ovarian cancer previously treated with platinum-based systemic therapy remains to be defined.
Adult↗
Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.
PURPOSE: To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS: We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS: With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION: Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.
Antineoplastic Combined Chemotherapy Protocols↗
Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.
PURPOSE: To evaluate the safety and pharmacology of the intraperitoneal (IP) administration of the antineoplastic agent taxol. PATIENTS AND METHODS: Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were no intrapatient dose escalations. RESULTS: The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. CONCLUSION: Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.
Alkaloids↗
Exploring the use of chronic low-dose oral etoposide in ovarian cancer: is there a role for this "new drug" in the management of platinum-refractory disease?
Despite showing high objective response rates (70% to 80%) to cisplatin- or carboplatin-based chemotherapy, most patients with ovarian cancer ultimately die of complications of their disease. Etoposide, given either as a single agent or in combination with the organoplatinum compounds, has produced disappointingly low response rates in the salvage setting. Based on recent data that suggest chronic administration of oral etoposide is superior to single daily dosing every 3 to 4 weeks, and the failure of previous trials to evaluate etoposide's activity in cisplatin-resistant malignancies, we have begun a phase II trial of chronic, low-dose oral etoposide in patients with clinically defined, platinum-resistant ovarian cancer. Thus far, 11 patients have been entered into the study. Neutropenia, the most prevalent toxicity, has precluded several patients from receiving the full 20-day course of 50 mg/d. No responses to treatment have been observed in nine evaluable patients. The study continues to accrue patients. The final results of this study and other trials should help determine the efficacy of chronic low-dose oral etoposide administration in patients with ovarian cancer.
Administration, Oral↗
Preparation and use of monoclonal antibodies in the detection of Trichinella spiralis circulating antigen.
In the present study, a trial was made to evaluate the monoclonal antibody produced as a tool in the detection of circulating antigen. For the preparation of monoclonal antibodies, four Balb/C mice were immunized with Trichinella spiralis larvae. Immunized spleen cells were prepared and a suitable mutant NS1 myeloma cell line was used for fusion. Eighty white swiss albino mice were orally infected with 500 L1 T. spiralis larvae. Their serum was collected at different periods i.e. 5, 11, 18 and 28 days post infection for the detection of circulating antigen which was done by the ELISA technique. Circulating antigen could not be detected on day 5 post infection, while on day 11 it was clearly identified; on day 18 it could be detected but at a lesser O.D. reading however the antigen disappeared completely on the 28th day. This study confirmed that monoclonal antibodies may be a valuable tool in the early diagnosis of trichinosis by the detection of specific antigens, even in small amounts whenever present in the circulation.
Animals↗
Raynaud's phenomenon in infertile women treated with bromocriptine.
Two cases are reported of infertile women who developed cold-induced digital vasospasm (Raynaud's phenomenon) on low-dose Parlodel (5.0 to 7.5 mg/day). The cases are reported to alert clinicians to the potential relationship between Raynaud's phenomenon and low-dose Parlodel usage in women using the drug for hyperprolactinemic or infertility indications.
Adult↗
Hypogonadotropic hypogonadism and delayed puberty in a man with anorexia nervosa.
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Adult↗
Calcium regulation of lysosomal proteolysis in skeletal muscle.
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Animals↗
Immunological investigation of visceral leishmaniasis among school children in Alexandria.
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Adolescent↗
Genetic algebras for tetraploidy with several loci.
The algebra of gamete multiplication corresponding to a population of autotetraploids which differ at n loci, each with an arbitrary number of alleles, is proven to be a genetic algebra, irrespective of the mode of segregation of the n loci.
Chromosome Mapping↗
Ethnic variation of genetic disease: roles of drift for recessive lethal genes.
Using Wright's distribution of gene frequencies for a recessive lethal gene, a method is given to analyze the probability that any particular gene frequency is greater than a given threshold gene frequency. The method is introduced to analyze the plausibility of drift for explaining observed data.
Computers↗
Cyclic hormonal changes in patients with congenital abscence of the uterus.
Our studies have shown normal cyclical patterns of ovarian steroids and pituitary gonadotropines in patients with congenital absence of the uterus. It appears that the life-long abscence of a functioning uterus has no effect on the functional life span of the corpus luterum, but may have some effect in the level of estrogenes in the second half of the cycle.
Adolescent↗