A longitudinal analysis of cytotoxic T lymphocyte precursor frequencies to the hepatitis B virus in chronically infected patients

Individuals with acute hepatitis B virus (HBV) infection characteristically mount a strong, multispecific cytotoxic T lymphocyte (CTL) response that is effective in eradicating virus. In contrast, this response in chronic carriers is usually weak or undetectable. Since it is generally acknowledged that HBV pathogenesis is immune-mediated, the occurrence of episodes of active liver disease in many carriers suggests that these individuals can mount active CTL responses to HBV. To see whether the detection of circulating CTLs is related to these flare episodes, we have determined the CTL precursor (CTLp) frequencies to HLA-A2-restricted viral peptides in seven patients over a 12-24-month period of their disease. Limiting dilution analyses (LDA) were performed longitudinally to five epitopes comprising the viral capsid (HBc), envelope (HBs) and polymerase (pol) proteins. Assays were performed against a mixture of peptides, or against each individual peptide, to measure overall CTL activity and the multispecificity of the responses, respectively. Since two of the patients were treated with recombinant human interleukin-12 (rHuIL-12) at the time, with one individual achieving complete disease remission a year later after being treated with interferon-alpha, we were also able to examine the effects of these cytokines on HBV cytotoxicity. Our results indicate that weak but detectable CTL responses do occur in chronic carriers which are generally associated with disease flares, although CTLps were also seen occasionally during minimal disease activity. The range of specificities varied between individuals and within each individual during the course of the disease. Finally, we also provide evidence that CTL reactivity is stimulated following treatment with certain cytokines, but is dependent on the time of administration.

Living with osteoarthritis: Patient expenditures, health status, and social impact

Objective. To determine out-of-pocket expenditures related to osteoarthritis (OA) and to explore whether demographic details, health status scores (Medical Outcomes Study 36-item Short Form [SF-36] and Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), or perception of social effect were expenditure determinants. Methods. A prospective cohort study of community-dwelling subjects with OA completed 4 consecutive 3-month cost diaries. In addition, subjects completed the SF-36 and WOMAC at baseline and at 12 months. Social impact at baseline was collected. Four groups categorized by age and sex were compared. Patients undergoing joint replacement were excluded. Results. Differences in health status were defined more by age than by sex, especially for physical function. The costs to the patients were high, particularly for women, who spent more on medications and special equipment. Women also reported receiving more assistance from family and friends. Higher disease-related expenditures were associated with greater pain levels, poorer social function and mental health, and longer duration of disease. Significant independent predictors of total patient expenditures related to OA were being female and having joint stiffness. Conclusion. Despite having heavily subsidized health care and access to the Pharmaceutical Benefits Scheme, out-of-pocket costs for patients with OA in Australia are considerable. Higher expenditures for patients with OA are related to more advanced disease, especially for women.

Acetazolamide poisoning in a toddler

Acetazolamide ingestion and its sequelae have not been previously reported in children. A 12-month-old girl, weighing 10 kg, developed metabolic acidosis following ingestion of between 500 and 1250 mg of acetazolamide. The maximum base deficit recorded was 11.6. She was treated with sodium bicarbonate and recovered completely. Accidental poisoning should be included in the differential diagnosis of a child presenting with metabolic acidosis.

Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age

Objective: To examine the effects of iron deficiency and its treatment by iron supplementation or a high iron diet on fatigue and general health measures in women of childbearing age. Design: Randomised controlled trial to compare supplement and dietary treatment of iron deficiency. Subjects: 44 iron deficient (serum ferritin < 15 mug/L or serum ferritin 15-20 mug/L, plus two of the following: serum iron < 10 mu mol/L, total iron binding capacity > 68 mu mol/L or transferrin saturation < 15%) and 22 iron replete (hemoglobin greater than or equal to 120 g/L and serum ferritin > 20 mug/L) women 18 to 50 years of age were matched for age and parity. Interventions: Iron deficient women were randomly allocated to either iron supplementation or a high iron diet for 12 weeks. Measures of Outcome: Iron deficient and iron replete participants had iron studies performed and completed the Piper Fatigue Scale (PFS) and the SF-36 general health and well-being questionnaire at baseline (TO), following the 12 week intervention (TI) and again after a six-month non-intervention phase (T2). The SF-36 includes measures of physical (PCS) and mental (MCS) health and vitality (VT). Results: MCS and VT scores were lower and PFS scores were higher for iron deficient women (diet and supplement groups) than iron replete women at baseline. Both intervention groups showed similar improvements in MCS, VT and PFS scores during the intervention phase, but mean increases in serum ferritin were greater in the supplement than the diet group. PCS scores were not related to iron status. Conclusions: Treatment of iron deficiency with either supplementation or a high iron diet results in improved mental health and decreased fatigue among women of childbearing age.

Low tacrolimus concentrations and increased risk of early acute rejection in adult renal transplantation

Background. A retrospective analysis was performed on adult renal transplant recipients to evaluate the relationship between tacrolimus trough concentrations and the development of rejection in the first month after transplant. Methods. A total of 349 concentrations from 29 patients, measured by enzyme-linked immunosorbent assay (ELISA), were recorded. Based on an increased serum creatinine, 12 patients were considered to have organ rejection. Rejection was confirmed by biopsy in five of these. The median trough concentration of tacrolimus over the first month of therapy, or until the time of first rejection was compared in rejecters vs non-rejecters. Results. Median trough concentrations of tacrolimus were found to be lower in biopsy-proven rejecters vs non-rejecters (P=0.03) and all rejecters vs nonrejecters (P = 0.04). The average median concentration (+/- SD) in the biopsy-proven rejecter group was 5.09 +/-1.16 ng/ml, compared to 9.20 +/-3.52 ng/ml in the non-rejecter group. After exclusion of an outlier, the average median concentration in all rejecters was 5.57 +/-1.47 ng/rnl, compared with 9.20 +/-3.52 ng/ml in non-rejecters. A rejection rate of 55% was found for patients with a median trough concentration between 0 and 10 ng/ml. This compared with no observed rejection in patients with a median concentration between 10 and 15 ng/ml. Conclusion. A significant relationship exists between organ rejection and median tacrolimus trough concentrations in the first month post-transplant, with patients displaying low concentrations more likely to reject. In order to minimize rejection in the first month after renal transplantation, trough concentrations greater than 10 ng/ml must be achieved.

Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer Information,

This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up. and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles

We recently demonstrated that suppression of bone remodeling allows microdamage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties at clinically relevant skeletal sites in the same dogs. Thirty-six female beagles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT), The remaining two groups were treated daily with risedronate at a dose of 0.5 mg/kg per day (RIS), or alendronate at 1.0 mg/kg per day (ALN) orally, The doses of these bisphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual-energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium were assigned to histomorphometry, The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L-4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (RIS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineralization, and significantly increased microdamage accumulation in all skeletal sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness of the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0.05) groups. When the two bisphosphonate groups were pooled in a post hoc fashion for analysis, this reduction in toughness reached statistical significance (p = 0.02), This study demonstrates that suppression of trabecular bone turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulation and a reduction in the intrinsic energy absorption capacity of trabecular bone. (C) 2001 by Elsevier Science Inc. All rights reserved.

The point-of-referral barrier - a factor in the success of telehealth

A feasibility study was carried out to test the hypothesis that, for an effective telehealth service, a full-time coordinator is required to act as a single point of contact for consultation requests. By shifting the responsibility for telepaediatrics from the referrer to the provider, the telehealth process becomes equally (or more) attractive as the conventional alternative. Preliminary results showed that, within six months, telepaediatric activity increased to an average of 8 h per month. Not only did certain health services become more accessible to children and their families in remote areas of Queensland, but significant savings were also made. At least 12 patient transfers were avoided to and from the tertiary facility, with an estimated minimum saving of $18,000 to the health-care provider.

Videoconferencing in the Queensland health service

Videoconferencing was introduced in the Queensland health service in 1995. By the end of 1999, there were more than 150 videoconferencing units in health facilities around the state. Six audits of videoconferencing usage were conducted using similar methodology at six-month intervals from November 1997 to May 2000. Between November 1997 and November 1999, the number of calls more than doubled, from 566 to 1378. Hours of usage almost trebled, from 671 to 1724. The average duration of calls remained similar, at about I h 12 min. The proportion of calls involving more than two sites (multipoint videoconferences) increased from 44% to 65%. The majority of the activity was for education (including training). Videoconferencing was also used for administration and clinical care. Mental health staff were the heaviest users, but use by health professionals from other specialty areas increased during the study period. The Queensland health service has realized a number of important benefits from telehealth.

The validity of an Australian modification of the AUDIT questionnaire

The Alcohol Use Disorders Identification Test (AUDIT) has been used widely and is reported to be superior to conventional questionnaires in detection of current hazardous and harmful alcohol use. We assessed the validity of an Australian modification of the AUDIT (the AusAUDIT), which has been employed widely in Australian and New Zealand early intervention programmes. We used a cross-sectional study of 370 subjects from the follow-up phase of a randomized controlled trial of early intervention to reduce hazardous alcohol consumption. Scores on the AusAUDIT were compared against 12-month ICD-10 diagnoses of harmful alcohol use and dependence, as determined by the Composite International Diagnostic Interview, and against self-report of alcohol consumption exceeding Australian National Health and Medical Research Council (NH&MRC) recommended limits. AusAUDIT had good internal consistency and discriminated significantly between persons meeting criteria for ICD-10 alcohol use disorders, and drinkers who did not. At currently recommended cut-off scores, AusAUDIT detected more than 85% of people meeting criteria for ICD-10 alcohol use disorders, or drinking over NH&MRC recommended limits, but its specificity was limited (29% in men, and 58% in women for drinking over NH&MRC limits). No subset of questions performed as well as the full AusAUDIT in detection of drinking problems, but the alcohol consumption items provided a reasonable screen for drinking over NH&MRC limits. We conclude that AusAUDIT is effective in detecting problematic drinking, but positive cases should be confirmed by clinical assessment. The findings illustrate the need for validation of questionnaire modifications, and the difficulty in increasing test sensitivity without reducing specificity.

Outcome of the acute abdomen in patients with previous spinal cord injury

Background: Patients with spinal cord injury (SCI) have always posed difficulties for the diagnosis of an acute abdomen. The aim of the present study was to define this problem retrospectively at Princess Alexandra Hospital and to assess the results of treatment for these patients. Methods: A retrospective review was conducted of 133 SCI patients admitted with an acute abdomen in the 16 years prior to this analysis at the Spinal Injuries Unit (SIU) of Princess Alexandra Hospital. There were 21 patients who conformed to the study criteria. All the patients had sustained traumatic SCI at or above the level of T11, more than 1 month prior to admission. Results: There were 13 male and eight female patients. The time lapse between SCI and the onset of an acute abdomen ranged from 1.5 months to 27 years. The age range was 26-79 years. The majority of patients had C6 injuries (six patients). There were 18 patients with injury levels above T6 and three patients with injuries below this level. The time taken to diagnose the cause of the acute abdomen ranged between 1 day and 3 months. Investigations were found to be useful in making the diagnoses in 61.9% of cases. There were 14 patients who had surgical interventions. Five patients had surgical complications and there were two deaths in the study. The length of follow up was 1-132 months. The mortality in the study was 9.5%. Conclusion: An aggressive approach to the diagnosis and treatment of the acute abdomen in SCI patients with suspicious symptoms is recommended. A high index of suspicion should be maintained in those patients with pre-existing SCI who present with abdominal trauma.

Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells

Prospective studies have shown rapid engraftment using granulocyte-colony-stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) for allogeneic transplantation, though the risks for graft-versus-host disease (GVHD) may be increased. It was hypothesized that the use of G-CSF to prime bone marrow (GBM) would allow rapid engraftment without increased risk for GVHD compared with G-PBSC. Patients were randomized to receive G-BM or G-PBSCs for allogeneic stem cell transplantation. The study was designed (beta < .8) to detect a difference in the incidence of chronic GVHD of 33% ( < .05). The plan was to recruit 100 patients and to conduct an interim analysis when the 6-month follow-up point was reached for the first 50 patients. Fifty-seven consecutive patients were recruited (G-BM, n = 28; G-PBSC, n = 29). Patients in the G-PBSC group received 3-fold more CD34(+) and 9-fold more CD3(+) cells. Median times to neutrophil (G-BM, 16 days; G-PBSC, 14 days; P < .1) and platelet engraftment (G-BM, 14 days; G-PBSC, 12 days; P < .1) were similar. The use of G-PBSC was associated with steroid refractory acute GVHD (G-BM, 0%; G-PBSC, 32%; P < .001), chronic GVHD (G-BM, 22%; G-PBSC, 80%; P < .02), and prolonged requirement for immunosuppressive therapy (G-BM, 173 days; G-PBSC, 680 days; P < .009). Survival was similar for the 2 groups. Compared with G-PBSC the use of G-BM resulted in comparable engraftment, reduced severity of acute GVHD, and less subsequent chronic GVHD. (Blood. 2001;98:3186-3191) (C) 2001 by The American Society of Hematology.

An evaluation of two indices of red fox (Vulpes vulpes) abundance in an arid environment

The suitability of spotlight counts to index red fox abundance was assessed in an arid environment through a comparison with a scat deposition index (active attractant). In most cases there was a high degree of correlation between the two indices, suggesting that the spotlight counts were accurately documenting fluctuations in population size. However, the precision of the spotlight index was often low (c.v. = 0.07-0.46), suggesting that the technique may not allow the statistical detection of small changes in abundance. During periods when there was an influx of new individuals into the population, the seasonal scat index displayed a three-month time lag in documenting abundance while foxes accustomed themselves to the presence of the regular food supply. The level of precision of the scat index was also found to be relatively low (c.v. = 0.21-0.48). Nevertheless, further refinements of this technique may produce a suitable measure of fox abundance.

Helping the female partners of men abusing alcohol: a comparison of three treatments

Aim. To evaluate the effectiveness of three approaches to assisting the female partners of male problem drinkers with the stress imposed by the male's drinking. Design. Participants were assigned randomly via random number tables to one of three treatment conditions: supportive counselling, stress management or alcohol-focused couples therapy. Setting. The intervention took place at the Behaviour Research and Therapy Centre (BRTC), The University of Queensland. This research and training centre offers outpatient psychology services to the community. Participants. Sixty-one married women whose husbands drank heavily. Participants reported protracted alcohol problems, severe impact of alcohol on social functioning and severe marital distress. Measurement. The women's stress, alcohol consumption by the male, and relationship functioning were assessed at pre- and post-treatment and at 6-month follow-up. Interventions. All three treatments involved 15 1-hour sessions with the woman. In the alcohol-focused couple therapy, attempts were made to engage the man in these sessions. Results. Contrary to our predictions, there were few differences between the treatments. All three treatments were associated with reductions in the women's reported stress, with trends for somewhat greater reduction in the women's stress in the stress management and alcohol-focused couples therapy conditions than for supportive counselling. None of the treatments produced clinically significant reductions in men's drinking or relationship distress. Conclusion. The treatments ease stresses and burden but do not improve drinking or relationships. Limited power in the design restricted the capacity to detect differential treatment effects.

The reduction of itch during burn wound healing

The purpose of this study was to find a method to reduce the itch experienced by patients who have sustained burn injuries, by using and comparing the effectiveness of 2 shower and bath oils. One product contained liquid paraffin with 5% colloidal oatmeal and the other contained liquid paraffin. The study was carried out in the Adult Burns Unit, Royal Brisbane Hospital (RBH), Brisbane. It was conducted during a 10-month period from July 1998 until April 1999. Thirty-five acute burns patients participated in an assessor-blind clinical trial. Patients were asked twice daily to rate their discomfort from itch and pain. The amount of antihistamine requested by each patient was totalled daily. Analysis of data supplied by patients showed that the group using the product with colloidal oatmeal reported significantly less itch and requested significantly less antihistamine than those using the oil containing liquid paraffin.