Further investigation of lead exposure as a potential threatening process for a scavenging marsupial species.

There is a growing recognition of the harmful effects of lead exposure on avian and mammalian scavengers. This can lead to both lethal and non-lethal effects which may negatively impact wildlife populations. Our objective was to assess medium-term lead exposure in wild Tasmanian devils (Sarcophilus harrisii). Frozen liver samples (n = 41), opportunistically collected in 2017-2022, were analysed using inductively coupled plasma mass spectrometry (ICP-MS) to determine liver lead concentrations. These results were then used to calculate the proportion of animals with elevated lead levels (>5 mg/kg dry weight) and examine the role of explanatory variables that may have influenced the results. The majority of samples analysed were from the south-east corner of Tasmania, within 50 km of Hobart. No Tasmanian devil samples were found to have elevated lead levels. The median liver lead concentration was 0.17 mg/kg (range 0.05-1.32 mg/kg). Female devils were found to have significantly higher liver lead concentrations than males (P = 0.013), which was likely related to lactation, but other variables (age, location, body mass) were not significant. These results suggest that wild Tasmanian devil populations currently show minimal medium-term evidence of exposure to lead pollution, although samples were concentrated in peri-urban areas. The results provide a baseline level which can be used to assess the impact of any future changes in lead use in Tasmania. Furthermore, these data can be used as a comparison for lead exposure studies in other mammalian scavengers, including other carnivorous marsupial species.

Deadly diving? Physiological and behavioural management of decompression stress in diving mammals.

Decompression sickness (DCS; 'the bends') is a disease associated with gas uptake at pressure. The basic pathology and cause are relatively well known to human divers. Breath-hold diving marine mammals were thought to be relatively immune to DCS owing to multiple anatomical, physiological and behavioural adaptations that reduce nitrogen gas (N(2)) loading during dives. However, recent observations have shown that gas bubbles may form and tissue injury may occur in marine mammals under certain circumstances. Gas kinetic models based on measured time-depth profiles further suggest the potential occurrence of high blood and tissue N(2) tensions. We review evidence for gas-bubble incidence in marine mammal tissues and discuss the theory behind gas loading and bubble formation. We suggest that diving mammals vary their physiological responses according to multiple stressors, and that the perspective on marine mammal diving physiology should change from simply minimizing N(2) loading to management of the N(2) load. This suggests several avenues for further study, ranging from the effects of gas bubbles at molecular, cellular and organ function levels, to comparative studies relating the presence/absence of gas bubbles to diving behaviour. Technological advances in imaging and remote instrumentation are likely to advance this field in coming years.

Risk of decompression sickness in extreme human breath-hold diving.

The risk of decompression sickness (DCS) in human breath-hold diving is expected to increase as dives progress deeper until a depth is reached where total lung collapse stops additional nitrogen gas uptake. We assembled a database of all documented human breath-hold dives to 100 metres or greater, including both practice and record dives. Between 1976 and 2006 there were 192 such dives confirmed by 24 divers (18 male, 6 female). The deepest dive was to 209 metres. There were two drowning fatalities, and two cases ofDCS. Depth-time risk estimates for DCS were derived for single breath-hold dives by modifying probabilistic decompression models calibrated with data from short deep no-stop air dives and submarine escape trials using maximum-likelihood estimation. Arterial nitrogen levels during apnea were adjusted for lung compression and decreased cardiac output. Predicted DCS risk is negligible up to about 100 metres, beyond which risk increases nonlinearly and reaches a plateau around 5 to 7 percent when total lung collapse occurs beyond 230 metres. Results are consistent with data available from deep breath-hold dives.

High blood lead concentrations in captive Tasmanian devils (Sarcophilus harrisii): a threat to the conservation of the species?

BACKGROUND: The Tasmanian devil (Sarcophilus harrisii) is the world's largest extant marsupial carnivore. Since the emergence of devil facial tumour disease in 1996, the species has undergone a severe population decline. The insurance population (IP) was established in 2006 to build a disease-free captive population to maintain 95% of the wild Tasmanian devil genetic diversity for 50 years. Captive and semi-wild Tasmanian devils are fed with possum and wallaby meat provided by local hunters, who use lead ammunition. Lead ingestion can cause acute toxicity, including ataxia, coma and death, or chronic subclinical deleterious effects including decreased fertility. METHODS: We determined blood lead concentrations in 26 captive and 133 wild Tasmanian devils from various sites across Tasmania. RESULTS: Captive Tasmanian devils showed significantly higher blood lead concentrations than their conspecifics in the wild. In captivity, older animals had higher blood lead concentrations than young animals, which suggested regular exposure, as lead can accumulate in a living organism in the blood, soft tissues and bones. After a response measure was implemented by removing the heads and wounds containing lead from the diet, blood concentrations significantly decreased in animals at one of the captive study sites, supporting the suspicion of food as the source of lead. CONCLUSION: This study highlights the need to ensure meat fed to captive carnivores is not contaminated by lead, especially in the context of a conservation program breeding individuals in captivity, as for Tasmanian devils.

Sirolimus-related pulmonary toxicity mimicking 'asthma like' symptoms.

Sirolimus is an immunosuppressant with expanding use in pediatric organ transplantation, dermatology and rheumatology. We report two cases of children who developed asthma like symptoms and were diagnosed with interstitial lung disease, which responded to discontinuation of sirolimus. Pediatricians should be aware about the pulmonary side effects of sirolimus.

Adverse events in competitive breath-hold diving.

Medical observations are reported from an eight-day world championship breath-hold diving competition involving 57 participants. The deepest dive was to 75 metres, and the longest breath-hold time exceeded 9 minutes. There were 35 diving-related adverse events witnessed or reported, including transient loss of motor control due to hypoxia, syncope during ascent, hemoptysis, and pulmonary edema. All events occurred in healthy individuals, and resolved without apparent sequelae. There was no relationship between symptoms and depth. The medical implications of these adverse events are discussed. Despite the inherent risks of the sport, established organizational procedures for competitive breath-hold diving maintain a high degree of safety.

A forgotten old disease: mediastinal tuberculous lymphadenitis in children.

OBJECTIVE: The purpose of the study was two-fold: (1) to highlight the varied presentation of mediastinal tuberculous lymphadenitis (MTL) in children and (2) to identify parameters, that may help in the early diagnosis of this condition. METHODS: Between January 1995 and December 2002, 13 children with histological diagnosis of MTL were retrospectively assessed for age at presentation, history of exposure to TB, presenting symptoms, investigations, initial diagnosis, surgical treatment and outcome. Stepwise multiple linear regression analysis was used to determine potential risk factors for early diagnosis of MTL. RESULTS: Thirteen children presented with: (a) fever, night sweats and weight loss (4); (b) acute respiratory distress (2); (c) cough and shortness of breath (SOB) (5); (d) stridor (1); and (e) chest pain (1). TB was suspected only in 6 children (46%) at presentation. In the other 7 cases (54%) the presumed diagnoses were: neuroblastoma (n=1), metastatic malignancy (n=1), bronchial polyp (n=1), bronchogenic cyst (n=2), and presumed foreign body (n=2). Bronchoscopy was diagnostic in identifying cheesy material within the bronchus and organisms on lavage in 4 (30%) and in identifying external compression in 2 (15%). Thoracotomy and excision of the lymph node mass was necessary to treat the mediastinal compression and to ascertain the diagnosis of TB in 3 children (23%). All 13 children had complete resolution of tuberculous lymphadenitis following anti-tuberculous treatment. The diagnostic clues in this cohort of patients were cough and SOB with history of exposure to tuberculosis (P=0.0001) and bronchoscopy and lavage with positive staining for acid-fast bacilli (P=0.0001). CONCLUSIONS: Tuberculosis was not suspected in 54% of children with MTL, and they posed diagnostic dilemma on admission. Bronchoscopy must be used as a diagnostic tool in children where tuberculosis cannot be excluded by radiology or specific skin tests. Thoracotomy and excision may be necessary to treat the obstructive symptoms.

Revised estimates of diagnostic test sensitivity and specificity in suspected biliary tract disease.

BACKGROUND: The purpose of this study was to estimate the sensitivity and specificity of diagnostic tests for gallstones and acute cholecystitis. METHODS: All English-language articles published from 1966 through 1992 about tests used in the diagnosis of biliary tract disease were identified through MEDLINE. From 1614 titles, 666 abstracts were examined and 322 articles were read to identify 61 articles with information about sensitivity and specificity. Application of exclusion criteria based on clinical and methodologic criteria left 30 articles for analysis. Cluster-sampling methods were adapted to obtain combined estimates of sensitivities and specificities. Adjustments were made to estimates that were biased because the gold standard was applied preferentially to patients with positive test results. RESULTS: Ultrasound has the best unadjusted sensitivity (0.97; 95% confidence interval, 0.95 to 0.99) and specificity (0.95; 95% confidence interval, 0.88 to 1.00) for evaluating patients with suspected gallstones. Adjusted values are 0.84 (0.76 to 0.92) and 0.99 (0.97 to 1.00), respectively. Adjusted and unadjusted results for oral cholecystogram were lower. Radionuclide scanning has the best sensitivity (0.97; 95% confidence interval, 0.96 to 0.98) and specificity (0.90; 95% confidence interval, 0.86 to 0.95) for evaluating patients with suspected acute cholecystitis; test performance is unaffected by delayed imaging. Unadjusted sensitivity and specificity of ultrasound in evaluating patients with suspected acute cholecystitis are 0.94 (0.92 to 0.96) and 0.78 (0.61 to 0.96); adjusted values are 0.88 (0.74 to 1.00) and 0.80 (0.62 to 0.98). CONCLUSIONS: Ultrasound is superior to oral cholecystogram for diagnosing cholelithiasis, and radionuclide scanning is the test of choice for acute cholecystitis. However, sensitivities and specificities are somewhat lower than commonly reported. We recommend estimates that are midway between the adjusted and unadjusted values.

Detection of HIV-1 in human lung macrophages using the polymerase chain reaction.

We have used the polymerase chain reaction to investigate HIV-1 infection of lung macrophages from 44 AIDS patients with pneumonia. Proviral HIV-1 DNA was detected in the lung macrophages of 47% (21 of 44) of patients tested; 32% (seven of 21) of the patients had Pneumocystis carinii pneumonia (PCP), and 56% (11 of 21) had pneumonia caused by other aetiological agents. Matched peripheral blood specimens were obtained from 22 patients in this study, and HIV-1-specific DNA was detected in 100% (22 out of 22) of non-adherent white cell preparations tested. HIV was detected in blood monocytes of 11 out of 22 patients (50%), and a virus signal was also found in the lung macrophages of eight of these patients. Our results indicate that PCP does not predispose lung macrophages to HIV-1, nor does HIV-1 infection of lung macrophages increase the probability of contracting PCP.

The epidemiology of HIV-1 infection of the lung in AIDS patients.

OBJECTIVE: To examine the relationship between HIV-1 infection of cells obtained by bronchoalveolar lavage (BAL) from the lung and the pathogenesis of AIDS. DESIGN: Prospective study of 121 consecutive HIV-1-seropositive patients undergoing investigation for respiratory symptoms or abnormal chest radiograph. METHODS: Polymerase chain reaction (PCR) for the detection of HIV-1-specific proviral DNA. Cocultivation of leukocytes obtained from BAL with donor cord blood leukocytes (CBL) to isolate HIV-1. RESULTS: HIV-1 was detected by PCR in the lung cells of 78 out of 121 (65%) patients. It was detected in 55% of patients who had been seropositive for less than 1 year, but in over 80% of patients who had been seropositive for more than 3 years. HIV-1 was isolated from 61 out of 106 (58%) individuals. The ability to detect or isolate HIV-1 from the lung correlated directly to CD4 cell count in peripheral blood. HIV-1 was detected significantly more frequently in the BAL cells of smokers compared with non-smokers (P = 0.01). CONCLUSIONS: HIV-1 was frequently detected and isolated from the lung of AIDS patients undergoing a respiratory episode. HIV-1 infection of the lung became more frequent with time from serodiagnosis. Patients who smoked were more likely to succumb to HIV-1 infiltration into the lung and HIV-1 infection of the lung was associated with progression to death.

Impact of baseline polymorphisms in RT and protease on outcome of highly active antiretroviral therapy in HIV-1-infected African patients.

OBJECTIVE: To assess the therapeutic response and investigate the significance of polymorphic codons in African patients receiving highly-active antiretroviral therapy (HAART). DESIGN AND METHODS: African patients were identified from the St Mary's Hospital HIV-1 database. Clinical outcome was assessed by viral load and CD4 cell count. Pre- and post-therapy sequences of RT and protease were analysed. The impact of subtype and individual polymorphic codons on therapeutic outcome was assessed statistically (Fishers exact and chi2 tests) and phylogenetically (Jukes and Cantor). RESULTS: Of 79 drug-naive African patients who were prescribed HAART, 60 remained undetectable for 1 year, with no differences detected in the clinical response to non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-containing regimes. Country of origin, sex and viral subtype had no impact on outcome of HAART. A total of 133 polymorphisms were identified in pol (37 in protease and 96 in RT), with a mean of 9.0 in protease and 22.3 in RT per patient. There was no significant difference in the overall numbers of polymorphisms per patient, and no single polymorphism had any impact on clinical outcome. Sequences from 'failing' patients experiencing viral rebound produced few mutations known to be associated with drug resistance, suggesting minimal drug pressure. CONCLUSIONS: The response of patients infected with African subtypes of HIV-1 to HAART appears to be independent of regime, HIV-1 clade and baseline polymorphisms. Non-B subtypes are fully sensitive to HAART and, accordingly, therapy should not be withheld from African patients for reasons of viral diversity.

Effect of HIV-1 and cytomegalovirus in bronchoalveolar lavage cells on the transfer factor for lung carbon monoxide in AIDS patients.

Abnormalities in pulmonary function tests have been observed in AIDS patients with pulmonary disease. In this study, the polymerase chain reaction (PCR) was used to determine if the reductions in transfer factor for lung carbon monoxide (TLCO) were due to the presence of HIV-1 or cytomegalovirus (CMV). HIV-1 was detected in cells from bronchoalveolar lavage (BAL) in 35 out of 60 (58%) of patients. The detection of HIV-1 had no significant effect on pulmonary function. CMV was detected in the BAL of 58% of patients in this study but CMV was the sole viral pathogen in the lung of only two out of 60 (3.3%) individuals. A significant reduction in TLCO was observed in individuals with PCP where CMV was also detected in the BAL. This study shows that reduction in TLCO in HIV-seropositive patients is not due to the presence of HIV-1 or CMV alone in BAL cells.

The rabbit study: ritonavir and saquinavir in combination in saquinavir-experienced and previously untreated patients.

Thirteen protease inhibitor-naive patients with HIV-1 infection, and 12 patients with a median of 58 months prior treatment with saquinavir (SQV) monotherapy, were treated with SQV (400 mg twice daily) and ritonavir (RIT, 500 mg twice daily) in a study designed to assess the effect of prior treatment with SQV monotherapy on the antiretroviral activity of RIT-SQV combination therapy. Median baseline viral load and CD4+ cell counts were 155,000 and 262,000 copies/ml and 333 and 225 cells/mm3 in the naive and experienced groups, respectively. Mean viral load changes at 24 weeks were -1.63 and -0.27 log copies/ml in the naive and SQV-experienced groups, respectively (intent-to-treat analysis). Baseline genotype by point mutation assay and sequencing in the SQV-experienced group was highly predictive of virological response. Eight of 11 SQV-experienced patients had evidence of phenotypic resistance to RIT at baseline, despite previous treatment with SQV only. There was strong correlation between phenotypic resistance to RIT and the presence of the L90M mutation. We conclude that prolonged prior treatment with saquinavir monotherapy may produce cross-resistance to ritonavir and reduce the subsequent response to ritonavir-saquinavir in combination. In this study, both phenotypic resistance to ritonavir and presence of the L90M mutation predicted the viral load response to ritonavir-saquinavir.

Role of the polar trophectoderm in determining the pattern of early post-implantation morphogenesis in mammals: evidence from development of the short-tailed field vole, Microtus agrestis.

The peri-implantational embryogenesis in the field vole, Microtus agrestis, is described. Implantation is interstitial, as it is in the mouse, but egg cylinder formation occurs by invagination of the blastocyst's embryonic pole and not (as in the mouse) by formation of a multilayered extra-embryonic ectoderm. This difference can be attributed to loss in the field vole of the central portion of the polar trophectoderm at the time of blastocyst attachment. In comparing early postimplantation development of mammalian species, three morphogenetic variables should be considered: (i) continued proliferation of polar trophectoderm; (ii) mechanical constraints on the direction of its growth; (iii) variations in the degree to which polar trophectoderm is maintained intact after implantation.

Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma.

BACKGROUND: The Tasmanian Asthma survey (TAS) and the International Study of Asthma and Allergies in Childhood (ISAAC) have used questionnaires to measure the prevalence of asthma in adults and children. We have investigated the validity of these questionnaires by comparing response to questionnaire with a physician assessment of asthma status in the past 12 months. METHODS: Ninety-three adults were given the TAS questionnaire to complete and 361 children were given the ISAAC questionnaire. Ninety-one adults and 168 children completed bronchial challenge with hypertonic saline. A consultation with a respiratory physician blinded to the results of the questionnaire and bronchial challenge was given to all subjects. RESULTS: In both adults and children, questionnaires showed high agreement with respiratory physician diagnosis with respect to asthma symptoms in the past 12 months. For the TAS questionnaire the positive and negative predictive values (95% confidence limits) for physician diagnosis for adults were 0.89 (0.68-0.98) and 0.94 (0. 86-0.98) respectively. The instrument was also sensitive 0.80 (0. 58-0.93) and highly specific 0.97 (0.90-0.99). For the ISAAC questionnaire the positive and negative predictive vales for physician diagnosis of asthma in children were 0.61 (0.50-0.71) and 0.94 (0.88-0.98) respectively. Sensitivity and specificity were 0.85 (0.73-0.93) and 0.81 (0.76-0.86) respectively. Compared to the physician diagnosis, the sensitivity of bronchial hyperresponsiveness (BHR) for asthma was low for adults 0.39 (0.21-0. 61) and children 0.54 (0.48-0.67) as were the positive predictive values: 0.55 (0.31-0.79) for adults and 0.64 (0.449-0.77) for children. A definition of asthma requiring both a positive questionnaire response and BHR was highly specific but not sensitive for adults 0.37 (0.20-0.59) or children 0.47 (0.35-0.60). CONCLUSIONS: Both the TAS and ISAAC questionnaires are valid instruments for the determination of asthma symptoms in the past 12 months.

The role of decision skills and medical knowledge in the clinical judgment of surgical residents.

Five surgical management problems amenable to solution by decision analysis were developed to test the decision-making skills, or surgical judgment, of residents in three university-based surgical training programs. Incorporated within the problems were indicators of textbook knowledge, basic computational ability and the ability to integrate probabilistic information in a logical decision-making process. Seventy-two residents representing 65% of those in the 5-year programs participated. Correct answers were determined by 50 senior surgeons and independently supported by the surgical literature and decision analyses. The percentage of correct surgical decisions averaged 72 +/- 3% until after the chief residency year, when it rose to 87 +/- 6%. Among the residents still in training, correct clinical decisions were associated with more accurate estimates of textbook information. The clinical recommendations of senior surgeons were consistent with the solutions of the problems by formal decision analysis in 92 +/- 2% of cases; the clinical recommendations of residents were consistent in 77 +/- 2% of cases. Decision analyses with appropriate use of textbook information could improve the accuracy of the residents' clinical recommendations. Decision analysis without accurate information resulted in inferior decision making for one of the management problems. Decision analysis can supplement, but not replace, the acquisition of scientific knowledge in the education of surgical residents.

Development of an objective rating system for residency applications.

A method was developed to include the opinions of all full-time surgical faculty in reproducible ratings of surgical residency applications according to five attributes: knowledge, judgment, technical skills, work habits, and interpersonal skills. Criteria for classifying each attribute on a scale of five intervals from deans' letters, recommendations, and interviews were developed and used to describe 25 theoretic applications. The applications were rated by each of 14 faculty members on a scale of 1 to 100. The value for each interval of each attribute was determined by conjoint measurement and verified with a second set of theoretic applications. The variation in the second set from faculty opinion was less than 1% (r2 greater than 0.99). The 56 applications for the four positions in our 5-year surgical training program were stripped of identifying information and rated objectively according to the criteria for classification and the values generated. The objective ratings correlated significantly (p less than 0.001) with the interview ratings of seven of the eight faculty interviewers. Variation of the objective ratings from the consensus of all full-time faculty was less than 1% (r2 greater than 0.99). Variation between the actual rank submitted to the National Resident Matching Program and that from the objective rating system was less than 1% (r2 greater than 0.99). As a result of our experience, we will be using this reproducible rating system for the preliminary ranking of our applicants next year.

Is there gender bias in the evaluation of surgical residents?

Although it might be assumed that the performance of surgical residents is assessed by faculty without regard to gender, no study to date has been undertaken to evaluate this. for 19 years, the Department of Surgery in our institution has had female faculty members to evaluate residents and, with the exception of 1969, female residents to be evaluated. All residents are evaluated by supervisory faculty after each clinical rotation. The same evaluation process has been used throughout this time, assessing residents on a five-point scale (1 = best) in each of six attributes: ethics, judgment, technical skills, knowledge, interpersonal skills, and work habits. The faculty evaluations of general surgery residents from academic years 1967 to 1985 were reviewed. A total of 2356 evaluations of 144 residents (22% female) by 69 faculty members (22% female) was available. For valid comparison, a subset of 702 evaluations was selected. Included were only those evaluations in which residents at the same level of training during the same academic year were evaluated by the same faculty members and in which both the resident and faculty groups had both male and female members. The average scores for male and female residents were nearly identical as determined by male and female faculty members, and no differences were statistically significant. In our program, with more than 20% women residents and faculty members over a 19-year period, no bias related to gender was demonstrated.