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Biomedical subjects

David Mahvi

Publications and source records attributed to David Mahvi.

7 recordsLinked to original sources

Gender disparities in colorectal cancer screening: true or false?

To date, nearly all studies examining gender disparities in colorectal cancer screening report a lower endoscopic screening rate in women. Using a statewide claims database, gender differences in screening rates were analyzed in an attempt to validate gender disparities reported in prior survey-based studies. Procedural-level dataset containing all patient encounters for 2003 in which a colonoscopy or flexible sigmoidoscopy were performed was created. Procedures were selected using CPT codes and univariate analysis was performed using SAS v 8.0. Statewide for average-risk individuals 50 years or older, 65,232 endoscopic procedures were performed in 2003. The majority (83%) of endoscopic screening procedures were colonoscopies. Overall, the rate of screening in average-risk women 50 years or older (38 procedures/1000 people) was slightly lower than in men (42/1000) but not statistically significant. The rates of screening were higher in women before the age of 60 years and lower after the age of 60 years. No clinically significant difference was found in the type of screening procedure performed. Gender disparities in rates and types of colorectal cancer screening reported in prior survey studies are not validated in this patient encounter data study.

Adult↗

Phase I trial of combined treatment with ch14.18 and R24 monoclonal antibodies and interleukin-2 for patients with melanoma or sarcoma.

PURPOSE: We conducted a phase I trial of interleukin 2 (IL-2) in combination with chimeric 14.18 (ch14.18) and murine R24 antibodies to determine the maximal tolerated dose (MTD), immunological effects, and toxicity of this treatment combination. EXPERIMENTAL DESIGN: Twenty-seven patients with either melanoma (23 patients) or sarcoma (4 patients) were enrolled to receive a combination therapy with ch14.18 and R24 antibodies together with continuous infusion of Roche IL-2 (1.5 x 10(6) U/m(2)/day, 26 patients) or Chiron IL-2 (4.5 x 10(6) U/m(2)/day, 1 patient) given 4 days/week for 3 weeks. The antibodies ch14.18 (2-7.5 mg/m(2)/day) and R24 (1-10 mg/m(2)/day) were scheduled to be administered for 5 days during the second week of IL-2 therapy. RESULTS: When given in combination in this study, the MTD for ch14.18 was 5 mg/m(2)/day and the MTD for R24 was 5 mg/m(2)/day. Dose-limiting toxicities were severe allergic reactions to both ch14.18 and R24 as well as pain related to ch14.18. This ch14.18 MTD was lower than the 7.5 mg/m(2)/day MTD previously determined for ch14.18 given alone with the same dose and schedule of IL-2. Immunological effects included the induction of lymphokine-activated killer (LAK) activity and antibody-dependent cell-mediated cytoxicity (ADCC). Anti-idiotype response to ch14.18 was seen in six patients, including two melanoma patients who had a partial response to treatment. In addition to two partial responses, four patients had a stable disease and one patient remained without any evidence of disease. CONCLUSIONS: Immunotherapy with IL-2 in combination with ch14.18 and R24 antibodies augments LAK function and ADCC measured in vitro in all patients. While there exist theoretical advantages of combining these two antibodies, the MTD of ch14.18 and of R24 were lower than the MTD of each antibody in prior studies evaluating single antibody therapy with IL-2. As such, the combination of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered antibodies.

Adult↗

Microwave ablation of hepatic tumors using dual-loop probes: results of a phase I clinical trial.

Hepatic tumors are a common cause of death worldwide. However, few patients are candidates for resection at the time of presentation. Microwave ablation is a viable alternative available for these patients. To date, only straight antennas are used for microwave ablation. Recently, a prototype loop-shaped microwave antenna was developed that, in animal studies, more effectively kills tumors. For this study, the dual-probe lesions were created by placing the probes in both tumors and normal livers. Lesions were created with 60 watts applied power for 5-7 minutes. The livers were sectioned and stained for viability. The average ablation volume was 63.9 +/- 8.7 cm(3). Microwave ablation with the loop probes results in complete tumor kill at the ablation/tumor interface, and adjacent to surrounding blood vessels. In addition, vessels within the ablation/tumor interface failed to show viable cells. The shape of the lesions was not distorted by proximity to blood vessels. The advantages of this configuration over conventional straight probes include the ability to encircle a tumor, deliver large amounts of precisely targeted microwave energy to the tumor, and spare normal liver outside the loop.

Equipment Design↗

Haemostatic partial nephrectomy using bipolar radiofrequency ablation.

OBJECTIVE: To determine whether an electrode array with a bipolar radiofrequency ablation (RFA) energy source can be used to perform a haemostatic partial nephrectomy by simultaneously ablating and coagulating renal tissue. MATERIALS AND METHODS: Lower-pole partial nephrectomy was performed in 12 porcine kidneys using a bipolar RFA system. Intraoperative ultrasonography was used to identify and avoid the collecting system. Tissues were positioned between opposing electrodes and tissue impedance monitored using a proprietary feedback and control algorithm. Ablation time and power, lesion width and length, and tissue thickness were recorded. The kidneys were assessed in vivo to show haemostasis of the remaining renal unit. Collecting system integrity was assessed with methylene blue injection, and the resected tissue analysed histologically. RESULTS: Partial nephrectomies were successful in all 12 porcine kidneys; the mean nephrectomy specimen was 3.2 x 2.6 cm. The total ablation time (sem) per lesion was 211 (15) s and the mean power was 23 W. Methylene blue injection showed an intact collecting system in 11 of the 12 kidneys, and haematoxylin and eosin staining showed a mean zone of necrosis of 9 mm at the resection margin. Ultrasonography revealed flow to the remaining kidneys after RFA and the in vivo assessment of haemostasis revealed no abnormal bleeding or haemorrhage from the kidneys. CONCLUSIONS: Applying bipolar RF energy to an electrode array can enable transmural excision of renal parenchyma in vivo in a bloodless fashion without collecting system injury.

Animals↗

Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients.

PURPOSE: To evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma. PATIENTS AND METHODS: Thirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d. RESULTS: Nineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex. CONCLUSION: Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.

Adult↗

Inguinal hernias, endometriosis, and other adverse outcomes in rhesus monkeys following lead exposure.

The Harlow Center for Biological Psychology (HCBP) has a cohort of rhesus monkeys that were exposed to low concentrations of lead acetate in utero or as infants. The lead-exposed animals have been followed for 19 years and have developed four cases of inguinal hernia (males), three cases of endometriosis (females), and one case of immunoblastic lymphoma (male). Retrospective analysis of the data from the original lead-exposed cohort indicates that there is a significant association between lead exposure and the development of inguinal hernia (P=.04). Endometriosis was not significantly associated with lead exposure (P=.36). A case control study also was done to determine the significance of neonatal lead exposure as a risk factor for the development of inguinal hernia and endometriosis. The risk of developing inguinal hernia was significantly increased in lead-exposed animals (OR=20.0, P=.009). The association between endometriosis and lead exposure was also strong (OR=10.13, P<.001). No unmatched variables were associated with inguinal hernia, including body weight, history of diarrhea, constipation, or intussusception. No unmatched variables were highly associated with endometriosis, including body weight, age at first parity, and history of stillbirths. However, parity and the number of stillbirths were associated with lead exposure (P=.011 and P=.041, respectively). There was an association between endometriosis and a history of hysterotomy (OR=2.09) but it was not statistically significant (P=.38). No other cases of lymphoma in unexposed animals were identified using HCBP animal health records. These data indicate that early lead-exposed rhesus monkeys may develop illnesses later in life, especially inguinal hernia and endometriosis, more frequently than unexposed monkeys. Studies of human populations with early lead exposure are warranted to determine their incidence of inguinal hernia, endometriosis, and hematologic neoplasia.

Animals↗