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Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 109 records · Page 6Linked to original sources
PubMed1996

A randomized phase II study of ifosfamide/mesna/cisplatin plus G-CSF or etoposide/cisplatin plus G-CSF in advanced non-small cell lung cancer: a Cancer and Leukemia Group B study.

This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be recommended with these chemotherapy regimens for patients with advanced NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Dirty, diseased and undeserving: the positioning of HIV positive women.

The discursive construction of HIV/AIDS associates deviance and disease. Women living with HIV/AIDS, in particular, have been positioned as a source or potential source of infection, and have attracted guilt and blame: in becoming 'disease' they have failed in their appropriate roles as carers and nurturers, responsible for the next generation. Based on in-depth interviews with 27 women living with HIV/AIDS this paper focuses on three ways of positioning HIV positive women: through discrimination on the part of medical professionals; through internalisation of stigmatisation; and through multiple stigmatisation of women who are or have been illicit drug users or sex workers. The implications of stigmatisation are discussed in relation to accessing health care and support.

Adaptation, Psychological↗
PubMed1996

Trends in heterosexual tertiary students' knowledge of HIV and intentions to avoid people who might have HIV.

This study investigated trends in HIV knowledge and endorsement of social avoidance of people who might be infected with HIV. The respondents (n = 7387) were self-identified heterosexual students. Most of them (n = 6500) were first-year behavioural or biological sciences students from annual surveys (1988-1995) at Macquarie University. The others (n = 887) were from four biennial (1987-1993) random samples of all students below 30 years of age at the University of Sydney. Students at both campuses completed self-administered questionnaires. Nine items were used to compute Partner Distinction Scale scores which indicated whether students had accurate knowledge that HIV may be transmitted through specific sexual practices with either casual or regular partners. Eleven items contributed to a Social Avoidance Scale. At Macquarie, male students had more accurate knowledge than female students, [F(1, 6024) = 9.20, p < 0.003], but at Sydney there were no significant sex differences in knowledge. Male students endorsed greater social avoidance at both Macquarie, [F(1, 6421) = 195.57, p < 0.00005], and Sydney, [F(1, 881) = 32.41, p < 0.00005]. Multiple linear regression on social avoidance revealed a significant reduction in social avoidance over time, with more rapid decrease among male students. Whereas less social avoidance was partly attributable to better knowledge over time, it is concluded that the improved social climate towards those most affected by HIV is mainly due to a shift in cultural norms.

Adult↗
PubMed1996

Sexual practice and understandings of safe sex: assessing change among 18- to 19-year-old Australian tertiary students, 1988 to 1994.

From 1988 to 1994, first-year students in a large introductory class at Macquarie University completed a questionnaire regarding sexual practice, knowledge of transmission of human immunodeficiency virus (HIV) and understandings of safe sex. Data from 18- and 19-year-old students were analysed to examine changes over time among recent school leavers. Approximately 58 per cent were sexually experienced, young men were more experienced than young women, and both had more experience with regular than with casual partners. The number of partners did not vary over the years, most respondents having had one or two partners. Changes over time were found with respect to condom use, particularly with regular partners. The percentage using condoms "always' with casual partners was greater, having increased to around 60 per cent. Accuracy of knowledge relating to safety of sexual practices with casual and with regular partners increased over time, particularly with respect to regular partners. While both accuracy of knowledge and safety of practice increased with time, there was no relationship between these two variables in any one year. The findings suggest that there has been normative change with regard to condom use and that this has occurred within a reasonably static and unchanging set of sexual practices. Sex education appears to be one of the factors contributing to this change.

Adolescent↗
PubMed1996

Dynamic mutation loci: allele distributions in different populations.

To assess the relative contributions of trans-acting factors (replication and repair functions) and cis-acting elements (repeat and flanking DNA composition) to the mechanism of trinucleotide repeat sequence mutation we have analysed the distribution of copy number polymorphisms at 12 loci associated with dynamic mutations in 15 populations of different ethnic origins. Genome wide instability of repeats in a particular population would be evidence of trans-acting factor instigation of the mutation process, whereas instability at a particular locus (perhaps even in several populations) would be evidence that the composition of the particular locus was the most significant factor contributing to mutation. The FRA16A locus is highly polymorphic in only the European population. Some other loci exhibit distinct distributions of alleles between different populations. Therefore sequences in the vicinity of the repeat -- the cis component of a particular locus -- appear(s) to be more important in the mutation mechanism than sporadic genome-wide instability induced by trans-acting factors such as the DNA mismatch repair enzymes.

Alleles↗
PubMed1996

Ambulatory sclerotherapy for malignant pleural effusions.

PURPOSE: To determine the feasibility of ambulatory drainage and sclerotherapy in malignant pleural effusions. MATERIALS AND METHODS: Nineteen consecutive patients with symptomatic malignant pleural effusions were enrolled. None of the patients previously underwent sclerotherapy. A fluoroscopically placed 10.3-F catheter was connected to a closed gravity drainage bag system. Sclerotherapy was performed with bleomycin when daily drainage was less than 100 mL. Radiographic response was graded at 30 days. All patients were examined for symptomatic response and for complications. RESULTS: The tubes remained in place 2-11 days (mean, 5.1 days). Total pleural drainage ranged from 950 to 3,925 mL (mean, 1,647 mL); all 19 patients had improvement of symptoms. At 30 days, 10 (53%) patients had a complete response, five (26%) had a partial response, and four (21%) had progressive disease. CONCLUSION: Ambulatory sclerotherapy is a safe, viable alternative to conventional inpatient treatment of malignant pleural effusions.

Ambulatory Care↗
PubMed1996

Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer.

PURPOSE: This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study. PATIENTS AND METHODS: Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy. RESULTS: The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions. CONCLUSION: This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.

Adult↗
PubMed1996

Update: vinorelbine (navelbine) in non-small cell lung cancer.

Vinorelbine (navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France), a novel semisynthetic vinca alkaloid, is the first drug approved by the Food and Drug Administration in over 20 years for the first-line treatment of ambulatory patients with unresectable advanced non-small cell lung cancer (NSCLS). In a multicenter, randomized US trial, single-agent vinorelbine produced response rates of 12%, compared with prior single-center studies demonstrating a response rate of 30%. Furthermore, in the US trial, median survival for patients receiving vinorelbine was 30 weeks, with a 1-year survival rate of 25%, compared with 22 weeks for 5-fluorouracil and leucovorin, with a 1-year survival rate of 16%. This impact on survival was confirmed in a European multicenter randomized trial. In this study, vinorelbine as a single agent demonstrated a median survival of 31 weeks, with a 1-year survival rate of 30%. Single-agent vinorelbine was comparable to the combination of vindesine/cisplatin, which had a median survival of 32 weeks and a 1-year survival rate of 27%. By contrast, the combination of vinorelbine/cisplatin produced a medial survival of 40 weeks and a 1-year survival rate of 35%. The major dose-limiting toxic effect of vinorelbine is granulocytopenia. Vinorelbine has demonstrated a survival advantage in patients with advanced NSCLC in two controlled clinical trials and has been associated with a favorable safety profile associated with a low incidence of hospitalization. These findings would suggest that vinorelbine alone or in combination with cisplatin may be a cost-effective treatment for appropriate patients with advanced NSCLC.

Agranulocytosis↗
PubMed1995

Human recombinant stem-cell factor induces melanocytic hyperplasia in susceptible patients.

BACKGROUND: Recombinant human stem-cell factor (SCF), a cytokine acting on hematopoietic progenitor cells, has potential for the treatment of several hematologic and oncologic disorders. In a hematology-oncology phase I trial of SCF, several patients had cutaneous hyperpigmentation at the SCF subcutaneous injection sites. OBJECTIVE: Our purpose was to investigate the pathogenesis of this hyperpigmentation phenomenon. METHODS: Skin biopsy specimens were obtained before, at the completion of, and after SCF therapy and were processed for histology, immunohistology, and electron microscopy. RESULTS: Skin at the site of SCF injection had an increased number of melanocytes, increased melanocytic dendrite extension, and melanin as compared with noninjected tissue. Immunohistochemical stains revealed an increase in staining with melanocyte-specific monoclonal antibodies HMB-45 and NKI/beteb, and a monoclonal antibody to the receptor for SCF, c-kit. CONCLUSION: Subcutaneous injection of SCF results in hyperplasia of melanocytes. SCF may be useful in the treatment of melanocytopenic disorders, but caution may be necessary in patients with disorders of melanocyte proliferation.

Antibodies, Monoclonal↗
PubMed1995

Predictors of unprotected male-to-male anal intercourse with casual partners in a national sample.

The focus of the paper is the predictors of unprotected anal intercourse with casual partners among a national Australian sample of homosexually active men. We interviewed by telephone 2583 homosexually active men (sex with a man within the last five years) about their sexual practice, type of sexual partners, human immunodeficiency virus (HIV) test status, attachment to the gay community, knowledge of HIV and acquired immune deficiency syndrome (AIDS) and a range of demographic variables. Logistic regression analyses were used to distinguish men who practised unprotected anal intercourse with casual partners from those who practised safe sex with casual partners. Men who practised unprotected anal intercourse with casual partners were less likely to have a regular male sexual partner than men who practised safe sex with their casual partners. They were less likely to be tertiary educated, more likely to be employed in trade and manual occupations and to live in Tasmania and the Northern Territory. They were less likely to be culturally or politically attached to the gay community. Knowledge of HIV/AIDS also distinguished the men: men with an accurate knowledge of HIV transmission were less likely to engage in unprotected anal intercourse with their casual partners. Several other variables, including age and HIV test status, did not distinguish those who practised safe sex with casual partners from those who practised unprotected anal intercourse with casual partners.

Australia↗
PubMed1995

Long-term consequences in offspring of diabetes in pregnancy: studies with syngeneic islet-transplanted streptozotocin-diabetic rats.

To study the long-term effects of exposure to maternal hyperglycemia and insulin deficiency in utero, we used the syngeneic islet transplanted streptozotocin-diabetic rat model of diabetes in pregnancy and examined insulin secretion and action in 6-month-old offspring. Female rats were rendered diabetic with streptozotocin and then transplanted with 2500, 750, or 500 islets. Control animals were also studied, and one group whose islet transplants failed remained diabetic. During pregnancy, plasma glucose levels in the diabetic rats and the groups receiving 500 and 750 islets were 24.7 +/- 1.0, 15.3 +/- 1.4, and 7.9 +/- 0.5 mmol/liter, respectively, all significantly greater than the control value (5.6 +/- 0.3 mmol/liter; P < 0.05). The plasma glucose level in the 2500 islet group was 6.2 +/- 0.2 mmol/liter, which was not significantly higher than the control value. When the offspring were studied at 6 months, there was no significant difference between groups in either glucose or insulin levels after iv glucose, although acute insulin secretion tended to be higher in the offspring of the diabetic animals. A study of insulin action with the euglycemic clamp at two insulin levels showed that insulin sensitivity was reduced in the offspring of diabetic animals vs. controls (1.97 +/- 0.24 vs. 7.58 +/- 0.95 mumol/liter x 100/kg/min.pmol/liter; P < 0.05). Insulin sensitivity was also significantly reduced in the 2500, 750, and 500 islet group offspring (4.81 +/- 0.57, 4.82 +/- 0.64, and 4.01 +/- 0.63 mumol/liter x 100/kg/min.pmol/liter; P < 0.05) compared to that in the control. There were no differences in insulin sensitivity between male and female animals. In summary, animals displaying maternal insulin deficiency have offspring who are insulin resistant without any evidence of iv glucose intolerance or diminished insulin secretion.

Animals↗
PubMed1995

The role of hematopoietic growth factors in support of ifosfamide/carboplatin/etoposide chemotherapy.

The ifosfamide/carboplatin/etoposide (ICE) combination represents an active chemotherapy regimen across a wide variety of disease types. The most common limiting toxicity for all three of these agents individually and in combination is myelosuppression. Thus, this regimen represents an ideal model to evaluate the role of hematopoietic growth factor support in amelioration of hematologic toxicity, maintenance of dose intensity, and dose escalation. While chemotherapy strategies using colony-stimulating factors have abrogated neutropenia, cumulative thrombocytopenia is common with many chemotherapy regimens, including ICE chemotherapy. In preclinical and phase II trials, monotherapy with recombinant human interleukin-6 (IL-6) has demonstrated substantial thrombopoietic activity, but with little enhancement of neutrophil recovery. Thus, this study was designed to evaluate combination cytokine therapy with both recombinant IL-6 and granulocyte colony-stimulating factor (G-CSF) after ICE chemotherapy. Previously untreated patients with inoperable non-small cell lung cancer are eligible. Treatment includes two monthly cycles of ifosfamide 2,000 mg/m2 with mesna 1,600 mg/m2 intravenously on days 1, 2, and 3, carboplatin 350 mg/m2 intravenously on day 1 only, and etoposide 75 mg/m2 intravenously on days 1, 2, and 3. All patients then receive G-CSF at a dose of 5 micrograms/kg/d subcutaneously beginning on day 4 until a postnadir absolute neutrophil count of more than 10 x 10(9)/L. Cohorts of patients (n = 15) are randomized to receive 0, 1, 2.5, or 5 micrograms/kg/d of IL-6 subcutaneously on days 4 to 13 in successive cohorts. This study has now reached its target accrual in all cohorts. The final data analysis is in progress. It is hoped that this trial will define the safety and tolerability of the simultaneous administration of IL-6 and G-CSF following ICE chemotherapy in patients with non-small cell lung cancer. In addition, this trial should determine the biologic activity and hematopoietic recovery observed during the simultaneous administration of these two cytokines in this setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Phase II study of neoadjuvant chemotherapy and radiation therapy with thoracotomy in the treatment of clinically staged IIIA non-small cell lung cancer.

BACKGROUND: The purpose of this study was to assess the ability of administering to patients induction chemotherapy with carboplatin and etoposide (VP-16), followed by full-course radiation therapy and weekly carboplatin with tolerable toxicity as preoperative therapy to down-stage disease thus allowing the resection of clinically staged IIIA non-small cell lung cancer. METHODS: Twenty-eight eligible patients with good performance status and previously untreated, marginally resectable stage IIIA non-small cell lung cancer received induction chemotherapy with carboplatin (dosed per the Egorin formulation), and VP-16 (100 mg/m2) followed by 6000 cGy of chest radiotherapy over six weeks administered concurrently with weekly doses of 100 mg/m2 of carboplatin. Patients who had either responsive or stable disease underwent thoracotomy, with attempted surgical resection of the primary lung lesion and the areas of abnormal adenopathy. Procedures involving less than a pneumonectomy were used whenever feasible. RESULTS: Fifty-two cycles of induction chemotherapy were administered. The average initial dose of carboplatin was 407 mg/m2. Toxicity was tolerable with grade 3-4 neutropenia and/or thrombocytopenia in 48 and 27% of the patients. There were no septic deaths. Full-dose radiotherapy was administered to 82% of patients, with 73% receiving at least five weekly doses of carboplatin. The radiographically assessed response rate to the neoadjuvant treatment was 64% (partial response, 46%; minimal response, 18%). Sixteen patients underwent gross tumor resection with 12 (43%) having negative pathologic margins. Six patients had pneumonectomy. There were three perioperative deaths (19%); two were secondary to respiratory failure after the patients underwent a pneumonectomy. The median survival for all 28 patients was 15 months, and for the 16 patients undergoing thoracotomy was 23 months. Eight patients were alive and in remission, with follow-up ranging from 8 to 31 months. CONCLUSIONS: The authors conclude that (1) carboplatin and VP-16, followed by full-dose radiotherapy with weekly carboplatin administration, is a well tolerated and effective regimen in the treatment of patients with marginally resectable stage IIIA non-small cell lung cancer; and (2) full-course radiotherapy can be administered before surgical resection without additional surgical morbidity or mortality.

Adult↗
PubMed1994

A pilot study of etoposide, vinblastine, and doxorubicin plus involved field irradiation in advanced, previously untreated Hodgkin's disease.

BACKGROUND: Advanced stage Hodgkin's disease (HD) usually is treated with combination chemotherapy with or without supplemental irradiation. The risk of significant acute and long term toxicity when the chemotherapy regimen contains alkylating agents has provided the impetus for the development of systemic combinations that do not include alkylating agents. This trial was designed to assess the toxicity and efficacy of a regimen of etoposide, vinblastine, and doxorubicin (EVA) as part of a combined modality approach in patients with moderate to high risk HD. METHODS: This was a prospective pilot study that included 26 previously untreated patients. They received 6 cycles of EVA, and complete responders received low dose (1500-2500 cGy) involved field radiation. RESULTS: Four patients were hospitalized for sepsis during chemotherapy. Complete response was achieved in 54% of patients, and 46% patients experienced induction failures. Two year failure-free survival is 44%, while 2 year overall survival is 86%. Median follow-up is 27 months. CONCLUSIONS: The EVA regimen is no more efficacious than other programs already in use and may be less so. It also is potentially leukemogenic because of the presence of etoposide. New combinations that do not contain etoposide should be explored in therapy programs for advanced HD in the hopes of discovering an efficacious treatment program that has minimal long term side effects.

Adolescent↗