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Biomedical subjects

D Holman

Publications and source records attributed to D Holman.

12 recordsLinked to original sources
PubMed2006

Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity.

Adenoviridae↗
PubMed2003

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

AIDS Vaccines↗
PubMed2003

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat.

Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 x 10(5) PFU/well of BMP viral vector was 4890 x 10(-12) U/well for ADCMVBMP-9, 302 x 10(-12) U/well for ADCMVBMP-4, 220 x 10(-12) U/well for ADCMVBMP-6, 45 x 10(-12) U/well for ADCMVBMP-2, and 0.43 x 10(-12) U/well for ADCMVBMP-7. The average volume of new bone induced by 10(7) PFU of BMP vector in athymic nude rats was 0.37+/-0.03 cm(3) for ADCMVBMP-2, 0.89+/-0.07 cm(3) for ADCMVBMP-4, 1.02+/-0.07 cm(3) for ADCMVBMP-6, 0.24+/-0.05 cm(3) for ADCMVBMP-7, and 0.63+/-0.07 cm(3) for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10(8) PFU induced 0.10+/-0.03 cm(3) of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10(7) PFU induced more bone, with an average volume of 0.29+/-0.01 cm(3).

Adenoviridae↗
PubMed1999

Use of a state data bank to measure incidence and prevalence of a chronic disease: end-stage renal failure.

The Western Australian Health Services Research Linked Database was used to examine trends in the incidence rate and prevalence of end-stage renal failure and to describe treatment patterns in these patients. Linked hospital morbidity and mortality records from 1980 to 1994 were selected if a record had a principal diagnosis or procedure of chronic renal failure, dialysis, or renal transplantation. Patient records were grouped according to the stage of care (predialysis, dialysis, transplant, or death). A total of 1, 046 patients with a principal diagnosis or procedure that met our criteria for end-stage renal failure was admitted to the hospital from 1985 to 1994. Trends in the incidence rate and prevalence of end-stage renal failure by sex and race, patterns of care, indices of comorbidity, and waiting time to transplantation were calculated. Results showed that both the incidence rate and prevalence of end-stage renal failure increased from 1986 to 1994, most noticeably in the aboriginal population. Rates of renal failure in 1994 were 15 times greater in aborigines than in nonaborigines. Of the hospital patients, 73.5% received dialysis three times a week. Complications associated with dialysis treatment were the most common cause of comorbid hospitalization. The mean waiting time to transplantation was 503 days for those who had a transplant and 6.3 years for all patients. The escalating numbers of patients undergoing renal dialysis, the high cost of maintaining them on dialysis, and the additional use of hospital services for comorbid conditions highlight the need to develop programs to prevent the occurrence of renal failure, particularly in the aboriginal population.

Adult↗
PubMed1998

A new rat model to study the correlation of cardiac and skeletal muscle allograft rejection.

As a first step to study the correlation of cardiac and skeletal muscle allograft rejection, we describe a new experimental rat model of simultaneous heterotopic heart and cutaneous maximus muscle flap allotransplant. Brown Norway rats were used as donors and Lewis rats as recipients. No immunosuppression was given. The grafts were revascularized with sequential end-to-side anastomosis of each vascular pedicle to the infrarenal aorta and vena cava. Syngeneic heart and cutaneous maximus muscle grafts remained functional and showed no sign of rejection at 7 days after the transplant. In contrast, both allografts developed severe rejection and functional compromise at 7 days after the transplant. Our experimental model is technically feasible and reproducible and may provide important information about the pattern of rejection of cardiac and skeletal muscle allografts.

Animals↗
PubMed1992

A survey of infertility, surgical sterility and associated reproductive disability in Perth, Western Australia.

Infertility, surgical sterility and associated reproductive disability were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Sixteen couples were omitted from analysis because of missing data. The proportion of couples affected by current infertility was 3.5 per cent (53 of 1,495), and 67.9 per cent of these (36 of 53) had a reproductive disability, meaning that they were unable to achieve their desired level of reproductive function. Those affected by surgical sterility accounted for 37.1 per cent (555 of 1,495), and of these couples 2.0 per cent (11 of 555) had a reproductive disability. Empirically, the prevalence of both infertility and reproductive disability peaked at ages 30 to 34 years in the female partner. Of the factors studied, infertility was associated with surgery for a ruptured appendix, a history of pelvic inflammatory disease and number of sexual partners. In 10 of the 47 couples with reproductive disability, contraceptive sterilisation had been a cause of later regret. Most other cases were due to infertility. Almost one half of couples with reproductive disability had sought treatment. The affected couples had at least one child from the current union in 23 of the 47 cases of reproductive disability. The results support the need for development of a strategy to prevent infertility and other causes of reproductive disability.

Adolescent↗
PubMed1992

A survey of contraceptive use and unplanned pregnancy in Perth, Western Australia.

Contraceptive use and unplanned pregnancy were studied in a stratified cluster sample of 1,511 couples with women aged 16 to 44 years resident in metropolitan Perth in 1988. Twenty-one couples were excluded from analysis owing to missing data. The proportion of couples using contraception was 76.8 per cent (1,144 of 1,490), and all but three of the remaining couples gave a reason for nonuse. Among users, surgical sterilisation made up 42.3 per cent (484 of 1,144) of all methods, with a slight predominance of tubal ligation over vasectomy. Oral contraceptives accounted for just over half of nonsurgical methods. Comparisons with a Victorian survey performed in 1978 suggested that surgical methods and condom use may have increased, whereas use of oral contraceptives and intrauterine devices may have fallen. Unplanned pregnancies conceived during the 12 months before the interview affected 3.4 per cent (51 of 1,490) of respondents. The incidence of unplanned pregnancy was four times higher in couples with inconsistent usage patterns of contraception.

Adolescent↗
PubMed1991

The effect of spine fusion on respiratory function in Duchenne muscular dystrophy.

Serial measures of respiratory function were made in 17 patients with Duchenne muscular dystrophy who underwent segmental spine fusion and in 22 patients who did not. No significant differences were observed between the 2 groups (operated vs. nonoperated) in terms of declining respiratory function. Nonetheless, all operated patients reported either improved sitting comfort, appearance, or both. Thus, our results suggest that there are distinct benefits from segmental spine fusion; however, there was no salutary effect upon respiratory function either in the short term or after up to 5 years follow-up.

Adolescent↗
PubMed1981

Increasing mortality from cancer of the cervix in young Australian women.

Mortality from uterine cancer in Australia has fallen progressively since 1908, as has mortality from cancer of the cervix specifically since it was distinguished, in statistics, from other uterine cancer in 1950. However, in women aged under 40 years, this trend has reversed recently, and cervical cancer mortality has risen since about 1970. This rise has also been shown by incidence data collected by the New South Wales Central Cancer Registry. Similar increases have been observed in New Zealand, Britain at least, appear to parallel increases in promiscuous sexual activity. Increases in the frequency of cervical cancer in older women can be expected when the cohorts affected (those born after 1935) reach older age groups.

Adult↗