Management of HIV/AIDS on the Mid North Coast: a collaborative model of care involving general practitioners and the public health system

ABSTRACT: The Coffs Harbour AIDS Information Network was set up to co-ordinate care planning and support service delivery for HIV/AIDS patients. This paper describes a collaborative model of care that brought together private general practitioners, a community nurse and a sexual health counsellor. Time involved in delivering services was monitored for each of the health professional groups during a 6 month period.
Twenty-three patients were involved in our study. Doctors averaged 23 min per consultation over 57 occasions of service. Travel or telephone contact took up 17% of the time spent on these patients. Corresponding figures for the nurse and counsellor were an average of 67 min over 144 services and 71 min over 16 services. They spent 16% and 27% of their time travelling or on the phone, respectively.
HIV/AIDS care is time consuming for health professionals but comprehensive care can be given in rural areas with adequate support and integration.     

Photomechanical delivery of 100-nm microspheres through the stratum corneum: implications for transdermal drug delivery

BACKGROUND AND OBJECTIVES: Photomechanical waves (PWs) render the stratum corneum permeable and allow molecules to diffuse into the epidermis. The aim of this study was to investigate the probe size that could be delivered through the stratum corneum and into the epidermis. STUDY DESIGN/MATERIALS AND METHODS: A single PW was applied onto the rat skin in vivo. Aqueous suspensions of fluorescent microspheres, 100 nm in diameter, were used as probes for transdermal delivery. The presence of the microspheres in the epidermis was measured by a fiber-based spectrofluorimeter after the stratum corneum was removed by tape-stripping (TS). RESULTS: Exposure of the rat skin to a PW permeabilized the stratum corneum and allowed the fluorescent microspheres to diffuse into the epidermis. CONCLUSIONS: The experiments show that PWs can facilitate the delivery of very large molecules and probes into the epidermis.     

Gene transfer into the central nervous system in vivo using a recombinanat lentivirus vector

Gene transfer vectors derived from human immunodeficiency virus (HIV-1) efficiently transduce nondividing cells and may provide for the delivery of their gene products to discrete regions of the brain. We investigated whether stable gene transduction can be achieved in cells of the central nervous system (CNS) in vivo by a potent lentivirus vector. The herpes simplex virus type 1 protein VP22 has been known to facilitate intercellular protein transport and thereby provides an opportunity to increase the effectiveness of therapeutic genes by enhancing the delivery of their protein products. We developed a lentiviral vector construct expressing enhanced green fluorescent protein (EGFP) fused at its N-terminus to the herpes simplex virus VP22. In order to determine expression of the fusion protein in specific cells such as neurons in the CNS, a neuron-specific promoter was also placed into the construct. The viral vectors were injected directly into the striatum and hippocampus of mouse brains. We found that the lentivirus vector efficiently and stably transduced nondividing cells in the CNS with transgene expression for over 3 months. We also show that the delivery of VP22-EGFP fusion protein encoded by the lentivirus was effectively transported between neuronal cells via axons in vivo. Doubly labeled experiments revealed that our lentiviral vector is capable of delivering gene products to neurons and astrocytes in CNS. The data also demonstrate that up to 90% of the CNS cells transduced by our lentiviral vector under the control of the neuronal promoter are neurons.     

Y1 receptor activation is involved in the effect of exogenous neuropeptide Y on pup growth and the early termination of lactational diestrus in the postpartum rat

The effect of chronic administration of exogenous neuropeptide Y (NPY) and specific NPY receptor agonists and antagonists on reproductive function was examined in lactating rats. As previously demonstrated in our laboratory, chronic (7-day) intracerebroventricular (i.c.v.) NPY infusion (6 microg/day) from days 8-15 postpartum (pp) caused a significant decrease in milk production and an early termination of lactational diestrus. Similar application of the mixed Y1/Y4/Y5 receptor agonist (Leu31, Pro34) NPY (at 3, 6 and 9 microg/day) reproduced the effect of chronic NPY infusion on milk production in a dose-independent manner. Consistent with this effect, the potent Y1 antagonist/Y4 agonist, 1229U91, given concomitantly with NPY eliminated the decline in milk production. The Y2 receptor agonist, NPY13-36, had no effect on milk production at any of the doses used. Length of lactational diestrus was reduced following administration of the Y2 agonist at 18 microg/day but not at 9 microg or 27 microg/day whereas (Leu31, Pro34) NPY infusion had no effect on this parameter at any of the doses used. However, the group that was treated with NPY plus 1229U91 exhibited the usual length of lactational diestrus, indicating that there is at least some Y1 involvement in the effects of NPY on lactational infertility. To test the possibility that the effects of NPY infusion are mediated through changes in circulating prolactin and progesterone, plasma concentrations of these hormones were measured on day 15 pp in NPY-, (Leu31, Pro34) NPY- and vehicle-treated females. NPY-infused females had lower plasma prolactin concentrations than vehicle-infused dams but progesterone concentrations were similar across groups. Overall, these data indicate that chronic exogenous NPY-infusion in lactating females disrupts milk production and shortens lactational diestrus, most likely through reducing prolactin secretion, and that this effect is mediated via Y1 receptor activity.     

Occupational injuries among Boston bicycle messengers

BACKGROUND: Urban bicycle couriers may have a high incidence of injuries. Most messengers work as contractors and hence their injuries are not well documented. METHODS: To quantify injury rates and severity among urban bicycle couriers a convenience sample of 113 couriers in the city of Boston completed a two-page self-administered survey. RESULTS: Most working couriers have suffered at least one injury resulting either in days lost from work (70%) and in visits to a health-care professional or hospital (55%). The annual incidence rate for injuries resulting in days away from work was 47/100-bike couriers. Bone fractures accounted for the most days lost from work, followed by dislocations, sprains, and strains. Collisions and avoiding collisions with motor vehicles, including being "doored," and collisions with pedestrians accounted for the majority (66%) of events leading to injury. Twenty-four percent of messengers reported wearing a helmet on a regular basis, and 32% have health insurance. CONCLUSIONS: Urban bicycle messengers are a poorly documented, largely unstudied workforce who suffer a very high rate of occupational injury.     

New Approach to Tumor Therapy for Inoperable Areas of the Brain: Chronic Intraparenchymal Drug Delivery

Because the brainstem has little functional redundancy, diffuse lesions have been regarded as inoperable. To determine whether local drug therapy can prolong survival in a rodent model of a tumor in such eloquent tissue, lethal doses of F98 and 9L tumor cells were injected into the brainstems of Fischer 344 rats. Five days after inoculations, 0.5 mg/ml solutions of carboplatin were infused at 1 l/h for 7 days. Compared to control groups that survived 13–17 days with F98 tumors and 22–23 days with 9L tumors, animals locally infused with 0.1 mg of carboplatin survived 27–30 days (Prob > Chi Sq = 0.0003), and 32 days (Prob > Chi Sq = 0.01), respectively. Measurements of tissue platinum levels at autopsy suggested that infusions distributed pharmacologically relevant levels of carbo-platin through a volume of tissue at least 0.5 cm in diameter. The results suggest that chronic low-flow infusions provide a promising approach to therapy for CNS lesions in tissues considered to be inoperable.     

Liposome-based drug delivery in breast cancer treatment

Drug delivery systems can in principle provide enhanced efficacy and/or reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the 'enhanced permeability and retention' effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardiotoxicity, and include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer treatment both as monotherapy and in combination with other chemotherapeutics. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immunoliposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies.     

A randomized trial of specialist genetic assessment: psychological impact on women at different levels of familial breast cancer risk

The aim was to compare the psychological impact of a multidisciplinary specialist genetics service with surgical provision in women at high risk and those at lower risk of familial breast cancer. Women (n=735) were randomized to a surgical consultation with (trial group) or without (control group) specialist genetic risk assessment and the possible offer of presymptomatic genetic testing. Participants completed questionnaires before and immediately after the consultation to assess anxiety, cancer worry, perceived risk, interest in genetic testing and satisfaction. Responses of subgroups of women stratified by clinicians as low, moderate, or high risk were analyzed. There were no significant main effects of study intervention on any outcome variable. Regardless of risk information, there was a statistically significant reduction in state anxiety (P<0.001). Reductions in cancer worry and perceived risk were significant for women at low or moderate risk (P<0.001) but not those at high risk, and satisfaction was significantly lower in the high risk group (P<0.001). In high risk women who received specialist genetic input, there was a marginally significant trend towards increased perceived risk. The effect of risk information on interest in genetic testing was not significant. Breast care specialists other than geneticists might provide assessments of breast cancer risk, reassuring women at reduced risk and targeting those at high risk for specialist genetic counselling and testing services. These findings are discussed in relation to the existing UK Calman-Hine model of service delivery in cancer genetics. DOI: 10.1038/sj/bjc/6600051 www.bjcancer.comCopyright 2002 The Cancer Research Campaign     

Pathways to care: help seeking behaviour in first episode psychosis

OBJECTIVE: To determine the number of attempts it took before patients with a first episode of psychosis received adequate help, the signs or symptoms that led them to seek help and the people from whom they attempted to seek help. METHOD: Subjects were 86 individuals with a schizophrenia spectrum disorder, mainly schizophrenia, who were attending a comprehensive program for early psychosis treatment. RESULTS: Help-seeking attempts began in the prodromal phase of the illness and continued into the psychotic phase. Concerning behaviours ranged from more general symptoms to psychotic symptoms. A range of contacts were made early on but emergency services were most often the contact that helped individuals obtain appropriate treatment for psychosis. CONCLUSION: Improved public education and gatekeeper education might reduce the time required for individuals developing a psychosis to receive timely and adequate care.