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Biomedical subjects

J Levi

Publications and source records attributed to J Levi.

At least 19 recordsLinked to original sources
PubMed2002

Phase I study of docetaxel plus ifosfamide in patients with advanced cancer.

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.

Adenocarcinoma↗
PubMed2001

Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome.

From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27 with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous hemangioma, and seven with mixed tumors of different diagnoses. Most often these lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic adenomas and mixed tumors were seen exclusively in females and FNH predominantly in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m: 52/19) relative to the other tumors (P < 0.001). Furthermore patients with hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma, FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25 patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There was no statistically significant correlation between symptoms and the size of the lesion, the final diagnosis, and whether there were solitary or multiple masses. Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%) with FNH had such a consequence. None of the hemangiomas presented with rupture or progressed to such a state. One patient with hepatic adenoma (4%) had a focus of malignancy. Surgical removal of benign tumors was performed in 82 of 130 patients (63%), and there was one operative mortality (1.2%) in a patient who had a caudate lobe FNH. The types of surgical procedures included segmentectomy (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had undergone laparotomy resection was not technically possible. Resection is recommended in all cases of hepatic adenoma because of fear of rupture or associated focus of malignancy. FNH was not observed to undergo a malignant transformation and will rarely rupture. Surgery is only recommended for symptomatic hemangioma, and size of the lesion is not a criterion for excision.

Adenoma, Liver Cell↗
PubMed2000

Extent of resection in the management of duodenal adenocarcinoma.

BACKGROUND: It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that pancreaticoduodenectomy (PD) is the procedure of choice, regardless of the tumor site. However, data from previous studies do not clearly support this position. METHODS: We reviewed the records of 63 patients treated for duodenal adenocarcinoma from 1979 through 1998. Perioperative outcome, patient survival, and extent of lymphadenectomy were compared in patients who underwent PD and SR. RESULTS: The overall morbidity for PD and SR was 27% and 18%, respectively (not significant [NS]). Patients who underwent SR had a 5-year survival of 60% versus 30% for patients who underwent PD (NS). Lymph node status was a prognostic factor for survival (P = 0.014). The mean number of lymph nodes in the specimens was 9.9 +/- 2.1 for PD and 8.3 +/- 4.4 for SR (NS). CONCLUSIONS: Segmental duodenal resection for patients with duodenal adenocarcinoma is associated with acceptable postoperative morbidity and long-term survival. The procedure is especially well suited for distal duodenal tumors. Clearance of lymph nodes and outcome are comparable to PD.

Actuarial Analysis↗
PubMed2000

HIV: challenging the health care delivery system.

HIV offers a lens through which the underlying problems of the US health care system can be examined. New treatments offer the potential of prolonged quality of life for people living with HIV if they have adequate access to health care. However, increasing numbers of new cases of HIV occur among individuals with poor access to health care. Restrictions on eligibility for Medicaid (and state-by-state variability) contribute to uneven access to the most important safety net source of HIV care financing, while relatively modest discretionary programs attempt to fill in the gap with an ever-increasing caseload. Many poor people with HIV are going without care, even though aggregate public spending on HIV-related care will total $7.7 billion in fiscal year 2000, an amount sufficient to cover the care costs of one half of those living with HIV. But inefficiencies and inequities in the system (both structural and geographic) require assessment of the steps that can be taken to create a more rational model of care financing for people living with HIV that could become a model for all chronic diseases.

Anti-HIV Agents↗
PubMed1999

Experience with staging laparoscopy in pancreatic malignancy.

BACKGROUND: The role of diagnostic laparoscopy in the staging of abdominal malignancies is not well defined. METHODS: We retrospectively reviewed the usefulness of diagnostic laparoscopy as a staging procedure in pancreatic malignancy. This experience between February 1988 and May 1997 involves 109 cases of suspected or proven pancreatic malignancy. All laparoscopies were performed with the patient under conscious sedation and local anesthesia in an endoscopy suite. RESULTS: Of the 109 patients with pancreatic cancer, 45 (42%) had metastatic disease. The use of computed tomography (CT) alone revealed the existence of liver metastases in 10 of 109 (9%) patients, which were confirmed laparoscopically. The further use of laparoscopy identified metastases in 29 more cases: hepatic, 23; hepatic and peritoneal, 3; peritoneal and mesenteric, 1; and mesenteric, 2. CT in conjunction with laparoscopy therefore revealed metastatic liver, peritoneal, or mesenteric lesions in 39 of 109 (36%) patients with pancreatic cancer. After staging laparoscopy, 67 of 69 patients underwent laparotomy. Metastatic disease was identified at laparotomy in 6 more patients; however, only 4 of these patients had metastases to the liver whereas 2 had metastases to the peripancreatic lymph nodes. Therefore, in patients with pancreatic malignancy, the negative predictive value for the diagnosis of metastases to the liver, peritoneum or mesentery was 94% (61 of 65 patients). The positive predictive value of laparoscopy alone for the detection of metastatic disease to the liver, peritoneum, or mesentery was 88% (29 of 33 patients). Laparoscopy was successfully performed without complications in all patients with pancreatic cancer; however, one had a technically unsatisfactory examination. The overall rate of resectability after staging by imaging studies and laparoscopy was 57% (35 of 61 patients). CONCLUSIONS: In patients with a negative CT for metastases, laparoscopic identification of metastases avoided unnecessary laparotomy in 29 of 99 (29%) patients with pancreatic cancer. Staging laparoscopy is indicated in all cases of pancreatic malignancy before an attempt at a surgical cure.

Aged↗
PubMed1999

Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin's lymphoma and advanced solid tumors.

BACKGROUND: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages. RESULTS: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir < 0.5 x 10(9)/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (< 25 x 10(9)/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity. CONCLUSION: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.

Adult↗
PubMed1999

Bone mineral density in patients with inflammatory bowel disease.

BACKGROUND: Studies have shown an association between inflammatory bowel disease (IBD) and low bone density. Previous publications, however, measured only a single parameter, either T or Z score, making comparison of data difficult. OBJECTIVE: To assess the effect of disease factors on both T and Z scores in a population of patients with IBD. METHODS: Risk factors for development of low bone density were recorded in IBD patients with confirmed diagnosis and disease extent. Bone density was then measured at the spine and neck of femur using dual-energy X-ray absorptiometry. RESULTS: Ninety-one patients (49 male, 42 female) with a mean age of 46.6 years (range 22-84) were studied. Forty-eight patients had ulcerative colitis and 43 had Crohn's disease. Mean Z scores were -0.60 at the hip and -0.61 at the spine, whilst mean T scores were - 1.61 at the hip and -1.15 at the spine. Univariate analysis of Z scores identified Crohn's disease, high steroid use and low BMI as significantly associated with low bone density. An identical analysis using T scores failed to show any significant relationships. On multivariate analysis of Z scores, only disease type and BMI remained significant. CONCLUSIONS: Low bone density is associated with IBD particularly in patients with Crohn's disease and low BMI. This large UK study is the first to report both T and Z scores in patients with IBD and shows that Z scores are the most reliable guide to the effect of IBD on bone density.

Adult↗
PubMed1999

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

PURPOSE: To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. RESULTS: A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). CONCLUSION: Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

Adult↗
PubMed1999

New approaches to HIV surveillance: means and ends. Summary report of conference held at Yale University, 21-22 May 1998, by the Law, Policy and Ethics Core, Center for Interdisciplinary Research on AIDS, Yale University.

A system of HIV surveillance based on AIDS case reporting is no longer adequate to monitor the epidemic of HIV/AIDS in the U.S. We are now faced with the challenge of designing an effective system of HIV surveillance. The "New Approaches to HIV Surveillance: Means and Ends" conference emphasized that there are several alternatives, each with strengths and limitations. The CDC has recommended that all states adopt a system of HIV surveillance based on case reporting. Although it has not specified that such systems need be name-based, CDC appears to reward states that adopt name-reporting systems. The rationale for this stance should be reviewed and made explicit. Name reporting may be superior in some respects to a system of case reports based on unique identifiers (UIs), especially in its greater ability to link surveillance activities to follow up at the individual level. Neither a name-reporting nor a UI approach to case reporting would provide HIV incidence data. The only currently envisioned means of providing incidence data is statistical estimation based on "snapshot estimates" of HIV incidence in sample cohorts. Calibration of this new instrument for HIV incidence estimation against existing data or through field trials is of critical importance.

Centers for Disease Control and Prevention, U.S.↗
PubMed1999

What do we need from surveillance? And how do we get it?

The Yale-hosted conference, "New Approaches to HIV Surveillance: Means and Ends," is now over two years old; it is time for the public health and AIDS community to move beyond the debate on name reporting and focus on rethinking what we need from surveillance and how we might best get it. Rethinking the role and methods of surveillance is critical for HIV; but it will also show the way for public health in general.

Confidentiality↗
PubMed1998

Identification of ATM mutations using extended RT-PCR and restriction endonuclease fingerprinting, and elucidation of the repertoire of A-T mutations in Israel.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, and radiation sensitivity. The responsible gene, ATM, has an extensive genomic structure and encodes a large transcript with a 9.2 kb open reading frame (ORF). A-T mutations are extremely variable and most of them are private. We streamlined a high throughput protocol for the search for ATM mutations. The entire ATM ORF is amplified in a single RT-PCR step requiring a minimal amount of RNA. The product can serve for numerous nested PCRs in which overlapping portions of the ORF are further amplified and subjected to restriction endonuclease fingerprinting (REF) analysis. Splicing errors are readily detectable during the initial amplification of each portion. Using this protocol, we identified 5 novel A-T mutations and completed the elucidation of the molecular basis of A-T in the Israeli population.

Ataxia Telangiectasia↗
PubMed1997

Improved quality of life with megestrol acetate in patients with endocrine-insensitive advanced cancer: a randomised placebo-controlled trial. Australasian Megestrol Acetate Cooperative Study Group.

PURPOSE: To investigate the effect of two doses of megestrol acetate (MA) compared with placebo on quality of life (QoL) and nutritional status (NS) in patients with advanced endocrine-insensitive cancer. PATIENTS AND METHODS: Two hundred forty patients were randomised to double-blind MA 480 mg/day, MA 160 mg/day, or matching placebo for 12 weeks. Nutritional status (including weight, skinfold thickness and midarm circumference) and QoL (using 6 linear analogue self-assessment (LASA) scales) were assessed at randomisation and after four, eight and 12 weeks. A QoL ranking incorporating QoL and death was also used ranging from 1 = dead to 5 = much better QoL. RESULTS: One hundred seventy-four patients were assessable at week four, 136 at week eight and 103 patients at week 12. Patients receiving MA reported substantially better appetite (P = 0.001), mood (P = 0.001) and overall quality of life (P < 0.001), and possibly less nausea and vomiting (P = 0.08) than patients receiving placebo, based on a test for trend. A larger benefit was seen with the higher dose which (unlike the lower dose) was significantly better in pairwise comparisons with placebo for appetite, mood and overall QoL (each P < or = 0.001). Despite some missing data on QoL scores, QoL ranking was available on 227 (95%) of patients with significantly higher QoL ranking associated with MA (P = 0.002). Improvements in QoL occurred early within four weeks and were sustained. No statistically significant differences were observed in NS measurements, including weight (P = 0.29). Side effects of therapy were minor and did not differ significantly across treatments. CONCLUSION: Megestrol acetate given at 480 mg/day is useful palliation in patients with endocrine-insensitive advanced cancer. It improves appetite, mood and overall quality of life in these patients, although not through a direct effect on nutritional status.

Aged↗
PubMed1997

Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol Investigational Trials Group, Australia and New Zealand.

When administered as a single agent in pretreated patients with advanced breast cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line therapy for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14, intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for six cycles (6 months). Patients whose disease progressed or relapsed were recommended to receive second-line epirubicin. Accrual has been completed with 208 patients randomized, but a preplanned interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by a linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months for paclitaxel-treated patients and 6.4 months for those given CMFP, with median survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4 neutropenia occurred in 64% of patients treated with paclitaxel and in 63% treated with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses. Nine percent of the patients had major infections with CMFP, but none were seen with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel-treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results on paclitaxel treatment as compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides comparable control of metastatic cancer to CMFP combination therapy when used as front-line treatment.

Antineoplastic Agents↗