A mathematical model of HIV transmission in NSW prisons

A mathematical model was developed to estimate HIV incidence in NSW prisons. Data included: duration of imprisonment; number of inmates using each needle; lower and higher number of shared injections per IDU per week; proportion of IDUs using bleach; efficacy of bleach; HIV prevalence and probability of infection. HIV prevalence in IDUs in prison was estimated to have risen from 0.8 to 5.7% (12.2%) over 180 weeks when using lower (and higher) values for frequency of shared injections. The estimated minimum (and maximum) number of IDU inmates infected with HIV in NSW prisons was 38 (and 152) in 1993 according to the model. These figures require confirmation by seroincidence studies. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.

Morphine has a dual concentration-dependent effect on K+-evoked substance P release from rat peripheral airways

Our previous investigations of possible lung mechanisms underlying the effectiveness of nebulized morphine for the relief of dyspnoea, have shown a high density of non-conventional opioid binding sites in rat airways with similar binding characteristics (opioid alkaloid-sensitive, opioid peptide-insensitive) to that of putative mu(3)-opioid receptors on immune cells. To investigate whether these lung opioid binding sites are functional receptors, this study was designed to determine (using superfusion) whether morphine modulates the K+-evoked release of the pro-inflammatory neuropeptide, substance P (SP), from rat peripheral airways. Importantly, K+-evoked SP release was Ca2+-dependent, consistent with vesicular release. Submicromolar concentrations of morphine (1 and 200 nM) inhibited K+-evoked SP release from rat peripheral airways in a naloxone (1 mu M) reversible manner. By contrast, 1 mu M morphine enhanced K+-evoked SP release and this effect was not reversed by 1 mu M naloxone. However, 100 mu M naloxone not only antagonized the facilitatory effect of 1 mu M morphine on K+-evoked SP release from rat peripheral airways but it inhibited release to a similar extent as 200 nM morphine. It is possible that these latter effects are mediated by non-conventional opioid receptors located on mast cells, activation of which causes naloxone-reversible histamine release that in turn augments the release of SP from sensory nerve terminals in the peripheral airways. Clearly, further studies are required to investigate this possibility. (C) 1997 Academic Press Limited.

Catecholamine release in heat-stressed Antarctic fish causes proton extrusion by the red cells

Two species of Antarctic fish were stressed by moving them from seawater at -1 degrees C to seawater at 10 degrees C and holding them for a period of 10 min. The active cryopelagic species Pagothenia borchgrevinki maintained heart rate while in the benthic species Trematomus bernacchii there was an increase in heart rate. Blood pressure did not change in either species. Both species released catecholamines into the circulation as a consequence of the stress. P. borchgrevinki released the greater amounts, having mean plasma concentrations of 177 +/- 54 nmol.l(-1) noradrenaline and 263 +/- 131 nmol.l(-1) adrenaline at 10 min. Pla.sma noradrenaline concentrations rose to 47 +/- 14 nmol.l(-1) and adrenaline to 73 +/- 28 nmol.l(-1) in T. bernacchii. Blood from P. borchgrevinki was tonometered in the presence of isoprenaline. A fall in extracellular pH suggests the presence of a Na+/H+ antiporter on the red cell membrane, the first demonstration of this in an Antarctic fish. Treatment with the beta-adrenergic antagonist drug sotalol inhibited swelling of red blood cells taken from temperature-stressed P. borchgrevinki, suggesting that the antiporter responds to endogenous catecholamines.

Sources of information about HIV/AIDS and perceived risk of infection among heterosexual young adults: 1989 and 1994

This paper reports a study of sources of information about HIV/AIDS and trust of the sources among heterosexuals in 1989 (113 females and 91 males) and 1994 (185 females and 66 males). We also examined whether perceived personal risk of HIV infection was predicted by sources of information about HIV/AIDS, trust of the sources, how informed about AIDS people believed they were, and perceived risk of infection to others, as well as whether there was a relationship between perceived personal risk and safe sex behaviour Participants received most of their information about AIDS/HIV from magazines, newspapers, and television, but placed most trust on sources such as doctors and HIV/AIDS organisations. Perceived personal risk was influenced most by perceived risk to friends and to people with the same sexual practices. In the 1994 sample, perceived personal risk was correlated with the amount of condom use among participants with sexual experience. These results indicate ther has been. relative stability across a five-year period. They also point to the continuing discrepancy among young heterosexuals between the most-used and most-trusted sources of information, as well as to the importance of peer influence on perceptions of personal risk of HIV infection.

The management of elderly patients with femoral fractures - A randomised controlled trial of early intervention versus standard care

Objective: To determine the effect of an early intervention program in an acute care setting on the length of stay in hospital of elderly patients with proximal femoral fractures. Setting: Acute orthopaedic ward of a large teaching hospital. Design and Participants: A randomised controlled trial comparing 38 intervention patients with 33 Standard Care patients. Intervention: Early surgery, minimal narcotic analgesia, intense daily therapy and close monitoring of patient needs via a multidisciplinary approach versus routine hospital management. Main outcome measures: Length of stay (LOS); deaths; level of independent functioning. Results: Mean LOS was shorter in the Intervention group than in the Standard Care group (21 days v. 32.5 days; P<0.01). After adjusting for other factors that could affect LOS (e.g. age, sex, pre-trauma functional levels, pre-trauma comorbidity and postsurgical complications), the Intervention program was significantly predictive of shorter LOS (P=0.01). The Intervention group did not experience greater numbers of deaths, deterioration in function or need for social support than the Standard Care group. Conclusion: This early intervention program in an acute care setting results in significantly shorter length of hospital stay for elderly patients with femoral fractures.

Sequence analysis of rabbit haemorrhagic disease virus (RHDV) in Australia: alterations after its release

Liver samples from rabbits killed by RHDV, collected from five States in Australia in 1996 and 1997 were analysed by RT-PCR. A 398 bp fragment of the capsid protein (VP60) gene was amplified by PCR and directly sequenced. The alignment of the nucleotide and amino acid sequences and their comparison with the original strain of the virus released in Australia indicated genetic changes after two years have been small with 98.2% to 100% identity. The constructed phylogenetic tree suggests slight differences in nucleotide substitutions in various States but there is no clear evidence of clustering of sequences according to their geographic origin. In practical terms, sequencing of viral RNA provides a means of testing the efficacy of further releases and subsequent spread of the virus if such a strategy is employed as a means of enhancing RHD as a biological control of the wild rabbit in Australia.

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa

Objective: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. Methods: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. Results: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. Conclusion: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic. (C) 1999 Lippincott Williams & Wilkins.

Molecular recognition of macrocyclic peptidomimetic inhibitors by HIV-1 protease

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a P-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 Angstrom N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba(67,95)]HIVPR and [Lys(7),Ile(33),Aba(67,95)]- HIVPR used in this work were shown to have very similar crystal structures.

HIV risk behaviour and prevention in prison: a bleach programme for inmates in NSW

One hundred and eighty-one inmates in AIDS education courses were surveyed about their risk behaviour and access to disinfectants for syringe cleaning in 1993, Overall, 40% of respondents reported HIV risk behaviour in prison. One-quarter of respondents reported injecting, of whom three-quarters reported sharing syringes in prison. Most respondents who shared syringes reported cleaning them with disinfectants (96%), even though only one-third reported having easy access to disinfectants. One-sixth of respondents reported sharing tattooing equipment, of whom two-thirds reported using a disinfectant to clean the tattoo needle. Few respondents reported fellatio (8%) or anal intercourse (4%) in prison. Although some respondents faced difficulty in obtaining disinfectants, almost all respondents cleaned syringes with bleach when sharing. High levels of risk behaviour in prison might be reduced by methadone maintenance and condom programmes. A trial of strict one-for-one syringe exchange warrants consideration.

Relapse and mortality among HIV-infected and uninfected patients with tuberculosis successfully treated with twice weekly directly observed therapy in rural South Africa

Objective: To determine post-treatment relapse and mortality rates among HIV-infected and uninfected patients with tuberculosis treated with a twice-weekly drug regimen under direct observation (DOT). Setting: Hlabisa, South Africa. Patients: A group of 403 patients with tuberculosis (53% HIV infected) cured following treatment with isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice weekly to 2 months and HR twice weekly to 6 months in the community under DOT. Methods: Relapses were identified through hospital readmission and 6-monthly home visits. Relapse (culture for Mycobacterium tuberculosis) and mortality given as rates per 100 person-years observation (PYO) stratified by HIV status and history of previous tuberculosis treatment. Results: Mean (SD) post-treatment follow-up was 1.2 (0.4) years (total PYO = 499); 78 patients (19%) left the area, 58 (14%) died, 248 (62%) remained well and 19 (5%) relapsed. Relapse rates in HIV-infected and uninfected patients were 3.9 [95% confidence interval (CI) 1.5-6.3] and 3.6 (95% CI 1.1-6.1) per 100 PYO (P = 0.7). Probability of relapse at 18 months was estimated as 5% in each group. Mortality was four-fold higher among HIV-infected patients (17.8 and 4.4 deaths per 100 PYO for HIV-infected and uninfected patients, respectively; P < 0.0001). Probability of survival at 24 months was estimated as 59% and 81%, respectively. We observed no increase in relapse or mortality among previously treated patients compared with new patients. A positive smear at 2 months did not predict relapse or mortality. Conclusion: Relapse rates are acceptably low following successful DOT with a twice weekly rifampifin-containing regimen, irrespective of HIV status and previous treatment history. Mortality is substantially increased among HIV-infected patients even following successful DOT and this requires further attention. (C) 1999 Lippincott Williams & Wilkins.