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Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 91 records · Page 5Linked to original sources

Gay men who engage repeatedly in unprotected anal intercourse with casual partners: the Sydney Men and Sexual Health Study.

We set out to determine the frequency and correlates of gay men's repeated unprotected anal intercourse with casual partners (UAI-C), defined as UAI-C reported at each of 3 annual interviews. By May 1997, 659 men had completed 3 annual interviews for the Sydney Men and Sexual Health (SMASH) cohort study. For the 3 6-month periods prior to each interview, 127 men reported UAI-C during one period only; 45 reported it during 2 periods; and 20 men reported it during all 3 periods. These 20 men who had repeated UAI-C were compared with 497 men who had anal intercourse with casual partners but did not report on all 3 occasions that they had UAI-C. Logistic regression revealed that repeated UAI-C was associated with HIV-positive status, more casual partners, less favourable attitudes toward condoms and greater recreational drug use. Few gay men have repeated UAI-C but those who do run greater risk of HIV transmission.

Adult↗

Irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer.

During the 1980s, platinum-based regimens were yielding response rates typically less than 25%, median survival durations of about 25 weeks, and 1-year survival rates less than 25% in patients with advanced non-small-cell lung cancer (NSCLC). Currently, results from single institution phase II trials of agents introduced in the 1990s show a doubling of these numbers, and results from multiinstitutional trials are demonstrating response rates ranging from 30% to 40%, median survival durations of 40 weeks, and 1 year survivals of 40%. Single agent irinotecan shows significant activity against NSCLC in preclinical and early phase I/II clinical studies, with activity similar to that for other new agents. Therapeutic synergy is observed in preclinical tumor models when irinotecan and cisplatin are combined, and phase I/II trials of this combination have demonstrated response rates > or = 50%. Herein the author provides an overview of data from phase II trials of irinotecan and focuses on preliminary results of a large US multicenter phase II trial of weekly irinotecan plus monthly cisplatin in 52 patients with advanced NSCLC. A response rate of 28.9% (95% CI, 16.5%-41.2%) and a median survival of 9.9 months were observed in this trial. US studies to design a more optimal irinotecan/cisplatin regimen in the same patient population are ongoing, and early results are encouraging.

Antineoplastic Agents↗

Hematopoietic growth factors in the reduction of chemotherapeutic toxicity.

Neutropenia is the most common dose-limiting toxicity of conventional chemotherapy. The colony-stimulating factors (CSFs), granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF, stimulate proliferation and maturation of myeloid progenitors and have been effective in reducing neutropenia and its complications. The primary use of CSFs in patients receiving chemotherapy for small cell lung cancer has resulted in a reduction in the incidence of febrile neutropenia, a decrease in the duration of grade IV neutropenia, and a reduction in hospitalization time and antibiotic use. Although CSF use allows for higher dose intensity, a survival benefit has not been proven. The use of CSFs after the occurrence of neutropenic fever decreases the duration of grade IV neutropenia, but effects on hospitalization and antibiotic use are less well-defined. The therapeutic use of CSFs in the setting of established neutropenia, regardless of the presence or absence of fever, is not supported in the literature. The administration of CSFs to patients with acute myeloid leukemia is safe in that no trial has demonstrated evidence of leukemic stimulation with these drugs. As in other settings, the duration of neutropenia is shortened if CSFs are used postchemotherapy with evidence of clinical benefit. CSFs also decrease chemotherapeutic toxicity via other mechanisms. The use of G-CSF reduces the incidence of mucositis, in normal donors enhances the yield of leukapheresis for granulocyte transfusion, and is beneficial in the autologous transplant setting. These effects of CSFs in mitigating chemotherapeutic toxicity are reviewed.

Antineoplastic Agents↗

Characteristics and consequences of free-feeding ethanol ingestion during the first two postnatal weeks of the rat.

The present experiment used a free-feeding technique devised by Hall to compare ingestion of ethanol and water during postnatal days 3 to 12. More intake of ethanol than water was observed, subject to reasonably consistent individual differences in ethanol intake unrelated to body weight or general fluid intake. Relative to Low ethanol consumers, pups that ingested higher quantities of ethanol showed less "place" aversion for stimuli associated with ethanol ingestion. High ethanol consumers did not, however, show an absolute conditioned place preference relative to water-only controls, and they exhibited a conditioned aversion to the odor of ethanol. These results indicate that ethanol intake during the first two postnatal weeks is modulated by the early occurrence of individual differences and a disposition to drink more ethanol than water, but the reinforcement effects of ethanol at this age are unclear.

Alcohol Drinking↗

Effects of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer.

BACKGROUND: Polyethylene glycol (PEG)-conjugated recombinant human megakaryocyte growth and development factor (MGDF, also known as PEG-rHuMGDF), a recombinant molecule related to thrombopoietin, specifically stimulates megakaryopoiesis and platelet production and reduces the severity of thrombocytopenia in animals receiving myelosuppressive chemotherapy. METHODS: We conducted a randomized, double-blind, placebo-controlled dose-escalation study of MGDF in 53 patients with lung cancer who were treated with carboplatin and paclitaxel. The patients were randomly assigned in blocks of 4 in a 1:3 ratio to receive either placebo or MGDF (0.03, 0.1, 0.3, 1.0, 3.0, or 5.0 microg per kilogram of body weight per day), injected subcutaneously. No other marrow-active cytokines were given. RESULTS: In the 38 patients who received MGDF after chemotherapy, the median nadir platelet count was 188,000 per cubic millimeter (range, 68,000 to 373,000), as compared with 111,000 per cubic millimeter (range, 21,000 to 307,000) in 12 patients receiving placebo (P = 0.013). The platelet count recovered to base-line levels in 14 days in the treated patients as compared with more than 21 days in those receiving placebo (P<0.001). Among all 40 patients treated with MGDF, 1 had deep venous thrombosis and pulmonary embolism, and another had superficial thrombophlebitis. CONCLUSIONS: MGDF has potent stimulatory effects on platelet production in patients with chemotherapy-induced thrombocytopenia.

Adult↗

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy.

BACKGROUND: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy. PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1-3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery. RESULTS: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment. CONCLUSION: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.

Adult↗

Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).

The maximum tolerated dose (MTD) of etoposide and carboplatin without growth factor support was previously defined by Cancer and Leukemia Group B (CALGB) as 200 and 125 mg/m2/day x 3, respectively, given every 28 days to previously untreated patients who have extensive, small-cell lung cancer (SCLC). Myelosuppression was dose-limiting. The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD. In this CALGB study of 44 evaluable patients with performance status 0-2, cohorts were treated with etoposide and carboplatin given intravenously on days 1-3 followed by GM-CSF (molgramostim) given subcutaneously on days 4-18. Four dose levels of bacteria-derived recombinant GM-CSF (5, 10, 20 microg/kg/day and 5 microg/kg every 12 h), three dose levels of etoposide (200, 250, and 300 mg/m2/day x 3), and two dose levels of carboplatin (125 and 150 mg/m2/day x 3) were evaluated. There was no chemotherapy dose escalation in individual patients. With 5 microg/kg/d GM-CSF, the first etoposide and carboplatin cycle of 300 and 150 mg/m2/day x 3, respectively, could be administered with acceptable toxicity. However, GM-CSF did not allow repeated administration of this dose-escalated regimen every 21 days, since delayed platelet and/or neutrophil recovery was dose limiting in later cycles. These results demonstrate that GM-CSF alone has limited capability to support the repeated administration of high doses of etoposide and carboplatin. CALGB currently is testing the ability of interleukin (IL)-6 given with GM-CSF to ameliorate the cumulative myelosuppression of this intense regimen.

Adult↗

Safety of concomitant use of granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor with cytotoxic chemotherapy agents.

Most studies that use recombinant granulocytopoietic cytokines, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), with the intent of attenuating neutropenia generally have delayed the administration of the cytokine until 24 to 72 hours following completion of chemotherapy. This practice was initiated out of theoretic concern that colony-stimulating factor administration may cycle and differentiate a population of normal cells, thus increasing their susceptibility to cycle-specific antineoplastic agents. The theory, in fact, has been substantiated by evidence from several clinical trials of concurrent administration. Thus, simultaneous administration of chemotherapy and G-CSF or GM-CSF should be limited to investigational protocols with scientific objectives, such as cycle compression or malignant cell sensitization.

Animals↗

A rapid molecular method (polymerase chain reaction with sequence-specific primers) to genotype for ABO blood group and secretor status and its potential for organ transplants.

We hypothesize that kidneys from non-secretor blood group A2 donors may be used for transplant into non-A recipients. In addition, we believe that organs from A2 donors may be used in non-A recipients where the anti-A titer is low. In order to reliably identify non-secretor A2 kidneys from cadaver donors, we have developed a rapid molecular method. The PCR-SSP-based method was developed to genotype ABO blood group and secretor status. Samples of known blood group ABO and Lewis phenotype determined by standard serological methods were used to appraise the method. A retrospective renal cadaver donor study was conducted to assess the potential of using A2 non-secretor organs for transplantation into non-A recipients. Phenotype frequencies of blood group A donors were 76% and 24% for A1 and A2 subgroups respectively, whereas 27% of the donor sample population were non-secretors. Three donors were identified as A2 non-secretors, and analysis was performed to theoretically place the organs by considering them as blood group O. These results coupled with a detailed analysis of HLA type and antibody status of our panel suggests that using A2 donors would be a useful adjunct to strategies for transplanting highly sensitized patients and redressing the donor-recipient imbalance in terms of blood group.

ABO Blood-Group System↗

Sexual practices in a broad cross-sectional sample of Sydney gay men.

The aim of this study was to provide current data on the sexual practices in a broad cross-sectional sample of gay and homosexually active men in Sydney. Anonymous, short questionnaires were completed by 1611 gay men recruited at the 1996 Gay and Lesbian Mardi Gras Fair Day or at one of six venues (including two sexual health centres) across the metropolitan area during the following week. The sample was diverse, but the men tended to be of Anglo-Australian background, well educated, professionally employed, attached to gay community and gay identified. They mainly had sex with other men rather than with men and women. Most (86.0 per cent) had been tested for human immunodeficiency virus. Excluding 241 men recruited in sexual health centres, 11.2 per cent were HIV-positive and 73.4 per cent were negative. Where it occurred in regular relationships, unprotected anal intercourse was usually between seroconcordant partners (78.5 per cent). Unprotected anal intercourse between discordant or nonconcordant regular partners was much less common, and in about half the cases involved withdrawal prior to ejaculation exclusively rather than ejaculation inside. Almost 12 per cent of the men had at least 'occasionally' engaged in unprotected anal intercourse with a casual partner in the previous six months, with approximately half of these men having adopted a withdrawal strategy on every occasion. We conclude that short surveys can provide valuable and timely data on sexual practices in a broad cross-sectional sample of gay and homosexually active men. Key messages for those involved in gay men's education are the high rates of unprotected anal intercourse between casual partners and the extensive practice of withdrawal.

Adolescent↗

Critical steps in instrument cleaning: removing debris after sonication.

To effectively clean and reuse instruments, dental personnel must pay close attention to all aspects of cleaning and sterilization procedures. This study addressed ultrasonic instrument cleaning and final rinsing. Results show that an ultrasonic solution can become increasingly contaminated with debris after each successive load of instruments is cleaned. The authors conclude that thorough rinsing of instruments after sonication in preparation for sterilization markedly reduces carry-over of detectable organic debris.

Blood↗

A phase II study evaluating the efficacy of carboplatin, etoposide, and paclitaxel with granulocyte colony-stimulating factor in patients with stage IIIB and IV non-small cell lung cancer and extensive small cell lung cancer.

We initiated a phase II pilot study to determine whether adding paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to combination carboplatin/etoposide is tolerable and active in patients with advanced non-small cell lung cancer and extensive small cell lung cancer. Patients were given carboplatin (area under the concentration-time curve of 6) followed by etoposide 80 to 100 mg/m2 intravenously on days 1 through 3 followed by paclitaxel 200 mg/m2 intravenously over 3 hours on day 3. On days 4 through 18, granulocyte colony-stimulating factor 5 microg/kg was administered subcutaneously. Each cycle was repeated every 21 days. Fourteen patients have been accrued to the study and 12 were evaluated for toxicity, the first 10 of whom were treated with 80 mg/m2 etoposide. Among the first 10 evaluable patients, significant grade 4 neutropenia occurred in one patient, grade 4 thrombocytopenia in three patients, grade 2 neuropathy in two patients, and grade 3 neurotoxicity in two patients. None of the four patients with non-small cell lung cancer responded to treatment, while six of seven small cell lung cancer patients have obtained major responses to therapy. We have increased the etoposide dose to 100 mg/m2 in subsequent patients. The combination chemotherapy regimen of carboplatin, etoposide, and paclitaxel is tolerable and active in patients with small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Gay youth and their precautionary sexual behaviors: the Sydney men and sexual health study.

Many commentators have positioned Western gay youth as a high-risk group for HIV infection and obscured important cultural, social, and contextual differences between populations. This study compares risk of HIV transmission factors among 216 young (under 25 years) and 822 older (25 years or over) homosexually active men, recruited through Sydney gay community and other sources. Bivariate and multivariate analyses of survey data that were collected by personal interviews consistently supported our hypothesis of no difference in HIV-related risk factors between young and older men. Although young men in this cohort were more likely to be of unknown serostatus, they were at least as knowledgeable, as attached to gay community, and as precautionary in their sexual behaviors with regular and casual male partners as their older counterparts. Safety campaigns targeting these young gay men should focus, for example, on their lower rates of HIV antibody testing and not be based on a false premise of hedonistic, uninformed, and disenfranchised youth.

AIDS Serodiagnosis↗