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Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 37 records · Page 2Linked to original sources
PubMed2002

Clinical uses of pegylated pharmaceuticals in oncology.

A number of agents that are used in the treatment of cancer have a suboptimal pharmacokinetic profile that necessitates prolonged or repetitive administration. Pegylation of these agents may help overcome these shortcomings without compromising the agents' efficacy. Several such pegylated agents have now been developed and evaluated in patients with oncology-related disorders. Pegfilgrastim (a pegylated form of filgrastim) has shown efficacy and tolerability that are at least equivalent to those of filgrastim in patients with chemotherapy-induced neutropenia and, unlike unmodified filgrastim, is effective with only one administration per chemotherapy cycle. Other promising pegylated agents are pegylated liposomal doxorubicin, which appears to be more effective and less cardiotoxic than unmodified or liposome-encapsulated doxorubicin, and peginterferon alpha-2a, as once-weekly treatment for renal cell carcinoma. Pegylated agents are likely to be more convenient for patients than the standard formulations, and the improved pharmacokinetics will enhance the clinical utility of these agents.

Adult↗
PubMed2002

In a minority of gay men, sexual risk practice indicates strategic positioning for perceived risk reduction rather than unbridled sex.

The aim of this analysis was to examine gay men's sexual risk practice to determine patterns of risk management. Ten cross-sectional surveys of gay men were conducted six-monthly from February 1996 to August 2000 at Sydney gay community social, sex-on-premises and sexual health sites (average n = 827). Every February during this period, five identical surveys were conducted at the annual Gay and Lesbian Mardi Gras Fair Day (average n = 1178). Among the minority of men who had unprotected anal intercourse which involved ejaculation inside with a serodiscordant regular partner, there was a clear pattern of sexual positioning. Few regular couples were both receptive and insertive. Most HIV-positive men were receptive and most HIV-negative men were insertive. Among the minority of men who had unprotected anal intercourse which involved ejaculation inside with casual partners, there was also a pattern of sexual positioning. Whereas many casual couples were both receptive and insertive (especially those involving HIV-positive respondents), among the remainder HIV-positive men tended to be receptive and HIV-negative men tended to be insertive. These patterns of HIV-positive/receptive and HIV-negative/insertive suggest strategic risk reduction positionings rather than mere sexual preferences among a minority of gay men. If so, they point not to complacency but to an ever more complex domain of HIV prevention.

Adolescent↗
PubMed2002

Increasing proportions of Australian gay and homosexually active men engage in unprotected anal intercourse with regular and with casual partners.

We examined trends in sexual practice among gay and homosexually active men in Australia. Self-complete questionnaires were distributed with mail-order sex video catalogues in 2000 and returned anonymously through a reply-paid facility. The data were compared with those from men who responded to promotional material sent out with the same catalogues and who participated in national telephone surveys of men who have sex with men conducted in 1992 and 1996. A key independent variable was gay community attached (GCA) versus non-GCA (NGCA) derived from two items about number of gay friends and amount of free time spent with gay men. Responses came from 1,832 men ranging in age from 16 to 80 (median = 39) years. HIV status was 73% negative, 5% positive, 22% untested; 1,181 men were GCA and 651 men were NGCA. Overall, from 1992 to 2000 there was a significant upward trend in the proportion of men reporting any unprotected anal intercourse (UAI) in the previous six months with regular partners: 21.5%, 24.7%, 46.4% of the total sample (p < 0.001). And similarly for UAI with casual partners: 12.4%, 16.2%, 25.5% (p < 0.001). The upward trends in UAI-regular and UAI-casual were similar and significant (p < 0.001) for both GCA and NGCA men. These nationwide Australian data provide evidence of continuing increases in unprotected anal intercourse with regular and with casual partners. Whereas the majority of men do not engage in any unprotected anal intercourse during a defined interval, ever increasing proportions of them do.

Adolescent↗
PubMed2002

Hemiarthroplasty versus internal fixation for displaced intracapsular hip fractures in the elderly. A randomised trial of 455 patients.

A total of 455 patients aged over 70 years with a displaced intracapsular fracture of the proximal femur was randomised to be treated either by hemiarthroplasty or internal fixation. The preoperative characteristics of the patients in both groups were similar. Internal fixation has a shorter length of anaesthesia (36 minutes versus 57 minutes, p < 0.0001), lower operative blood loss (28 ml versus 177 ml, p < 0.0001) and lower transfusion requirements (0.04 units versus 0.39 units, p < 0.0001). In the internal fixation group 90 patients required 111 additional surgical procedures while only 15 additional operations on the hip were needed in 12 patients in the arthroplasty group. There was no statistically significant difference in mortality between the groups at one year (61/226 versus 63/229, p = 0.91), but there was a tendency for an improved survival in the older less mobile patients treated by internal fixation. For the survivors assessed at one, two and three years from injury there were no differences with regard to the outcome for pain and mobility. Limb shortening was more common after internal fixation (7.0 mm versus 3.6 mm, p = 0.004). We recommend that displaced intracapsular fractures in the elderly should generally be treated by arthroplasty but that internal fixation may be appropriate for those who are very frail.

Aged↗
PubMed2002

Production of inhibin A not B in rams: changes in plasma inhibin A during testis growth, and expression of inhibin/activin subunit mRNA and protein in adult testis.

Previous studies have shown that changes in the plasma concentrations of immunoreactive inhibin measured by radioimmunoassay occur in parallel with growth and regression of the testes during a reproductive cycle in adult Soay rams induced by exposure to an artificial lighting regimen of alternating 16 week periods of long days and short days. With the development of new two-site ELISAs for sheep inhibin A and inhibin B, we have re-examined the relationship between FSH and dimeric, biologically active inhibin in the reproductive cycle in adult Soay rams. No signal was generated by sheep testicular extract, ram or ewe plasma, or sheep ovarian follicular fluid in the inhibin B ELISA. In contrast, ram plasma contained significant activity in the inhibin A ELISA, which diluted in parallel to the inhibin A standard, and was abolished by preincubation of ram plasma with monoclonal antibodies specific for the betaA, but not the betaB, subunit. These results indicate that the ram is the first adult male mammalian species identified to date in which the testes produce and secrete dimeric inhibin A and not inhibin B. Northern blot analysis and immunocytochemistry confirmed the presence of alpha, betaA and betaB inhibin/activin subunit mRNA and protein in the testes of adult rams. Changes in plasma inhibin A concentrations occurred in parallel with the growth and regression of the testes during the long day: short day: long day lighting regimen in adult Soay rams, confirming our previous observations with immunoreactive inhibin. During the growth phase of the testes in the first 8 weeks of exposure to short days there was a positive correlation between plasma FSH and inhibin A concentrations, indicating that during this phase the secretion of inhibin A is stimulated by FSH and that inhibin A did not act as a negative feedback hormone on FSH secretion. From week 8.5 to week 16.0 of exposure to short days, there was a negative correlation between FSH and testosterone concentrations, but not inhibin, indicating that when inhibin concentrations are high, testosterone acts as the negative regulator of FSH secretion. Thus, in intact adult rams, when the testes are fully active it appears that inhibin A may sensitize the pituitary to the negative feedback effects of testosterone, at which time they act synergistically to maintain plasma concentrations of FSH.

Analysis of Variance↗
PubMed2001

Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.

PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.

Adult↗
PubMed2001

Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions.

Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.

Breast Neoplasms↗
PubMed2001

Isolation, tissue distribution, and chromosomal localization of a novel testis-specific human four-transmembrane gene related to CD20 and FcepsilonRI-beta.

CD20 and the beta subunit of the high affinity receptor for IgE (FcepsilonRIbeta) are related four-transmembrane molecules that are expressed on the surface of hematopoietic cells and play crucial roles in signal transduction. Herein, we report the identification and characterization of a human gene, TETM4, that encodes a novel four-transmembrane protein related to CD20 and FcepsilonRIbeta. The predicted TETM4 protein is 200 amino acids and contains four putative transmembrane regions, N- and C-terminal cytoplasmic domains, and three inter-transmembrane loop regions. TETM4 shows 31.0 and 23.2% overall identity with CD20 and FcepsilonRIbeta respectively, with the highest identity in the transmembrane regions, whereas the N- and C-termini and inter-transmembrane loops are more divergent. Northern blot and RT-PCR analysis suggest that TETM4 mRNA has a highly restricted tissue distribution, being expressed selectively in the testis. Using fluorescence in situ hybridization and radiation hybrid analysis, the TETM4 gene has been localized to chromosome 11q12. The genes for CD20 and FcepsilonRIbeta have also been mapped to the same region of chromosome 11 (11q12-13.1), suggesting that these genes have evolved by duplication to form a family of four-transmembrane genes. TETM4 is the first nonhematopoietic member of the CD20/FcepsilonRIbeta family, and like its hematopoietic-specific relatives, it may be involved in signal transduction as a component of a multimeric receptor complex.

Alternative Splicing↗
PubMed2001

A sticky edge.

Explore the source record for details and available documents.

Adhesives↗
PubMed2001

Increasing realism among gay men in Sydney about HIV treatments: changes in attitudes over time.

It is important to know if optimism about HIV treatments is widespread and whether it is growing. To this end, cross-sectional surveys of gay men were conducted 6-monthly in Sydney between February 1997 and February 1999 (n = 3012). Recruitment was consistent at 4 gay community venues. The participants responded True, False or Unsure to 5 statements about the effectiveness of HIV treatments (2 items), and transmission (2 items) and 'worry' (1 item) in the context of treatments. In terms of effectiveness, HIV-positive men were more likely than non-positive men to dismiss 'cure' (P < 0.05) and more likely to support 'treatments prevent serious illness' (P < 0.001). Uncertainty about effectiveness decreased over time (P < 0.001 for each item). In terms of transmission, HIV-positive men were more likely than non-positive men to reject notions of reduced infectivity (P < 0.001). Over time, there was less uncertainty among non-positive men about undetectable viral load and transmission possibilities (P < 0.001). Overall, HIV-positive men were less 'worried' than non-positive men (P < 0.001) but there were no changes over time. On the whole, gay men in Sydney are now less uncertain about highly active antiretroviral therapies (HAART) than at the time of their introduction. Most men remain sceptical that these treatments can cure HIV infection and prevent HIV transmission, but in regard to managing illness among those infected, some initial uncertainty is being replaced by a growing optimism about the efficacy of treatments.

Adolescent↗
PubMed2001

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.

Aged↗
PubMed2001

Carboplatin/etoposide/paclitaxel in the treatment of patients with extensive small-cell lung cancer.

The purpose of this study was to examine the safety and efficacy of carboplatin/etoposide/paclitaxel in patients with untreated stage IV non-small-cell lung cancer (NSCLC) and extensive small-cell lung cancer (SCLC). Carboplatin was administered intravenously (i.v.) at an area under the curve (AUC) of 6 with etoposide at either 80 or 100 mg/m2 i.v. days 1-3 and paclitaxel at 175 or 200 mg/m2 i.v. over 3 hours along with 5 g/kg of granulocyte colony-stimulating factor subcutaneously on days 4-18, repeated every 3 weeks for 6 courses. Thirty-one patients (five NSCLC and 26 SCLC) entered into this phase I study. The median age was 63 (range, 42 to 74 years), with 24 males and seven females. The recommended dose level for phase II testing was carboplatin AUC = 6, etoposide 80 mg/m2 days 1-3, and paclitaxel 175 mg/m2 over 3 hours. With seven patients at this level, 14% had grade 4 neutropenia, 14% had grade 4 thrombocytopenia, none had grade 2/3 neurotoxicity, and no toxic deaths occurred. One of five (20%) patients with NSCLC responded, and 19 of 22 (86%) evaluable SCLC patients experienced a response to therapy. SCLC patients had a median survival of 10 months. The combination of carboplatin/etoposide/paclitaxel has significant activity with acceptable toxicity in patients with extensive SCLC.

Journal Article↗
PubMed2000

Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family.

A novel gene product, GPR74, with homology to the seven transmembrane-domain receptor superfamily, has been cloned. GPR74 has been identified from the expressed sequence tags (EST) database. Subsequent PCR amplification of that sequence and screening of a human heart cDNA library led to the isolation of a 1.7-kb cDNA clone encoding a protein of 408 amino acids. GPR74 shows highest amino acid identity (33%) to the human neuropeptide Y-receptor subtype Y2. The human and mouse genes for GPR74 have been isolated and their exon-intron structures determined. In both species the gene consists of four exons spanning around 20 kb with the exon-intron borders being 100% conserved. Northern analysis of various human tissues reveals highest levels of mRNA expression in brain and heart. In situ hybridisation analysis of rat brain tissue confirms this result and identifies the hippocampus and amygdala nuclei as the brain areas with particular high expression of GPR74 mRNA. Fluorescence in situ hybridisation, PCR analysis on a radiation hybrid panel and interspecific mouse backcross mapping have localised the genes to human chromosome 4q21 and mouse chromosome 5. Expression of the human GPR74 cDNA as a GFP-fusion protein in various cell lines reveals the inability of the recombinant receptor protein to reach the cell surface. This is consistent with the lack of NPY specific binding in these cells and suggests that unknown factors are required for a full functional receptor complex.

Amino Acid Sequence↗