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The health status of Australia's indigenous people remains the worst of any subgroup within the population, and there is little evidence of any significant improvement over the past two decades, a situation unprecedented on a world scale. Compared with non-indigenous Australians, adult life expectancy is reduced by 15-20 years, with twice the rates of mortality from heart disease, 17 times the death rate from diabetes and 10 times the deaths from pneumonia. Despite improvements in perinatal mortality, they continue to represent a major cause of death, with infant deaths up to 2.5 times higher than the general population. The problems of educational disadvantage and unemployment are reflected in twice the rates of smoking and high obesity levels. Seven percent of indigenous families are homeless, with many more in inadequate and overcrowded housing, sometimes lacking water or sewerage. Economic disadvantage is real: 23% worry about going without food. Nutritional deficiencies in children have resulted in failure to thrive, contributing greatly to the problems of pneumonia and infectious diseases. The remoteness and isolation of many Aboriginal communities limit education and employment opportunities. It is important to consider the historical context of Aboriginal and Torres Strait Islander people, in order to gain an understanding of current health problems. The impact of past policies and practices and the 'introduced diet' are reflected in the poor health outcomes described above. This session will explore some of the underlying historical, cultural, structural and political factors that can be linked to the current problems.
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PMID:Acculturation: Aboriginal and Torres Strait Islander nutrition. 1249 50

The strategy in the choice of antipsychotic agent must take into account the hepatic tolerance according to non-negligible incidence of liver disorders among psychiatric population (presence of risk factors like alcoholism, drugs of abuse intake, polymedication including potentially hepatotoxic drugs.). More than 1 000 drugs have been listed as being responsible of hepatic side effects; 16% of these agents were neuropsychiatric drugs. Antidepressive drugs (tricyclic agents or SSRI), mood stabilizing agents and neuroleptic drugs have been implicated in biological or/and clinical hepatotoxicity. For these reasons, some psychotropic agents have been withdrawn of the pharmaceutical market like alpidem or medifoxamine. Atrium*, sometimes used to correct tremor induced by neuroleptic drugs, has been withdrawn recently, as well. Isolated elevations of hepatic enzymes occur frequently with phenothiazines drugs (frequency evaluated to 20%) but also with other classes of neuroleptic agents, as well. On the contrary, clinical hepatitis have been more rarely described with neuroleptic drugs like phenothiazine agents (0,1-1%) or with haloperidol (0,002%). The definition of hepatotoxicity is based on biological parameters (elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT) or on clinical abnormalities (hepatitis, jaundice.). Clinical hepatitis could be either cytolytic or cholestatic. Clinical diagnosis and the research of its origin may include many investigations like abdominal ultrasonogram and percutaneous liver biopsy. The present article describes the cases of hepatic disorders reported with AAD (Atypical Antipsychotic Drugs), which are available in France (amisulpride, clozapine, olanzapine, risperidone). This new pharmacological class of antipsychotic drugs has showed great interest to improve negative symptoms of schizophrenia and to reduce disabling side effects like dystonia. According to the bibliographic data available, the following points and information must be clinically taken into account. Frequency of hepatic troubles: according to the bibliographic data, AAD appeared generally well tolerated in most cases. The frequency of hepatic troubles remains in general very low or rare. The cases published were observed with clozapine, olanzapine and risperidone. Nevertheless, some authors have observed higher frequency of hepatic enzymes elevation with some AAD. In an investigation comparing hepatic tolerance of clozapine (n=167) versus haloperidol (n=71), 37,3% of clozapine treated patients showed a relevant SGPT increase versus 16,6% with haloperidol. Nature of the hepatic troubles: among the clinical observations, asymptomatic biological disorders of the hepatic function are generally described but cytolytic or cholestatic hepatitis were reported, as well. Symptomatic hepatic dysfunctions were, sometimes, associated with other disorders like convulsions, pneumonia or malignant syndrome. Thus, hepatic check-up may be relevant in case of significant side-effect outcome. Delay time before the hepatic episode: hepatic injuries generally occurred within the first weeks of treatment but this delay highly varied in the literature from 1 to 8 weeks, 12 days to 5 months, 1 day to 17 months for clozapine, olanzapine and risperidone, respectively. These delay times are very similar to those observed with other psychotropic drugs. Reversibility of the hepatic troubles and rechallenge of the responsible agent: all cases were reversible after the AAD withdrawal except with one patient (39 years old) treated by clozapine (350 mg/day) who developed a fulminant and irreversible hepatitis after 8 weeks of monotherapy. In most cases, the AAD was withdrawn after the hepatic episode according to the significant risk of irreversible alteration. Nevertheless, normalization of hepatic enzymes has been described despite AAD maintenance at the same dosage or after dosage reduction. Rechallenge of clozapine after a first episode was performed for three patients, only one redeveloped a new hepatic disorder. According to different authors, special care is required if maintenance or rechallenge of the agent is indispensable after a first episode of isolated hepatic enzyme elevation (i.e resistance or intolerance to other treatments). In this case, biological and clinical supervision has to be carefully scheduled, which demands a satisfactory compliance from the patient. On the contrary, in case of clinical hepatotoxicity, rechallenge or maintenance is absolutely inadvisable. Mechanism of the hepatic troubles: precise mechanisms of the hepatotoxicity remain unclear. Contrary to phenothiazine drugs, no information is available on the respective rule of the agents and their metabolites. Hypersensitivity syndrome or eosinophilia has been reported, suggesting a possible immuno-allergic mechanism. Presence of risk factors: risk factors have been retrieved, in some observations, like high daily dosage, high plasmatic concentration, age, alcoholism, obesity or antecedent of hepatic disorders like Gilbert syndrome. Special care is advisable with these patients. As hepatotoxicity has been observed after surdosage (or suicide attempt), a hepatic check-up has to be performed in these clinical situations. Co-medication with hepatotoxic drugs may increase the risk as it has been suggested. In many observations, co-medication made difficult the incrimination of the AAD in the hepatic disorders outcome. Monotherapy has the great advantage to make easier the withdrawal of the responsible agent and its substitution. As drugs of abuse like cocaine or ecstasy are notoriously responsible of hepatotoxicity, they represent a probable factor of risk. Moreover, their detection is fundamental during the clinical investigation. Conclusion - Diagnosis of toxic hepatitis is mainly based on the chronology between agent introduction and hepatic disorder onset but other causes must be excluded. Bibliographic data analysis greatly contributes to confirm toxic hepatitis diagnosis. Nevertheless, this article emphasized the limits of bibliographic review to compare drugs towards tolerance. Most of the bibliographic data were case-reports for which it was sometimes difficult to provide absolute evidence of the responsibility of the agent. Moreover, spontaneous notification to health national administration is rarely systematic, in particular with isolated elevation of hepatic enzymes, and even more rarely published in international reviews. Nevertheless, according to the present data available in the literature, systematic and regular hepatic survey does not seem necessary in absence of risk factors. As for other side effects, which may occur more or less rapidly, great advantages may be obtained from psycho-education programs associating the patients in order to detect the first symptoms. Because little long-term hepatic follow-up comparing AAD is available, controlled studies should be carried out to precise the frequency and the risk factors (covariables) to prevent hepatitis outcome.
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PMID:[Hepatic tolerance of atypical antipsychotic drugs]. 1250 67

Although aspiration is a relatively rare event during anaesthesia, it represent an important cause of anaesthesia related mortality and also of ventilator associated pneumonia in intensive care unit. The incidence of aspiration is markedly increased after trauma owing to the risk of recent ingestion of food, depression of consciousness and airways reflexes, and gastric stasis induced by raised sympathoadrenal tone. The factors which contribute to the likelihood of aspiration include the urgency of surgery, airways problems, inadequate depth of anaesthetic, use of the lithotomy position, gastrointestinal problems, depressed consciousness, increased severity of illness and obesity. Factors that predispose to aspiration pneumonia are: a gastric content with a pH less than 2.5 and a gastric volume of 0.4 ml kg-1; a reduction in lower oesophageal sphincter tone; a reduction of upper oesophageal sphincter tone and a not coordination between the pharyngeal muscle and the upper oesophageal sphincter tone during swallowing; and a depression of protective airway reflexes. Methods to minimize regurgitation and aspiration involve control of gastric contents (preoperative starvation is the method universal accepted), application of cricoid pressure and control of the airways.
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PMID:Gastric reflux and pulmonary aspiration in anaesthesia. 1276 74

We report a 21-year-old woman with ectopic ACTH syndrome due to islet cell carcinoma with multiple liver metastases. On admission, she showed Cushingoid appearance (moon face, central obesity etc.) and had acute respiratory distress syndrome due to pneumocystis carinii pneumonia. Laboratory examination revealed marked elevations of plasma ACTH (735 pg/ml) and cortisol (145 microg/dl) with a profound hypokalemia (2.0 mEq/l). She was found to have multiple masses in the liver and a solid mass in the tail of pancreas by abdominal computerized tomography scanning. Treatment with octreotide successfully reduced elevated plasma ACTH and cortisol levels, and she received frequent transhepatic arterial embolization and chemotherapy. The primary pancreatic tumor was surgically removed, revealing islet cell carcinoma which contained high content of ACTH (100 microg/g wet weight) and abundantly expressed proopiomelanocortin and somatostatin receptor subtype-2 mRNAs as determined by Northern blot analysis. Postoperatively, she was free from symptoms for almost one year. However, progressive enlargement of multiple liver metastases refractory to chemotherapy led her to decide on total hepatectomy and liver transplantation from her father. After liver transplantation, she remained almost free from symptoms for almost one year. However, metastases developed to the mediastinal and paraaortic lymph nodes as detected by 111[In] pentetreotide scintigraphy. Eleven months after liver transplantation, she was again treated with octreotide and, 16 months after, with metyrapone, both of which were effective in reducing ACTH and cortisol levels, respectively, until she died of acute respiratory failure. This case of a young female patient with ectopic ACTH-producing islet cell carcinoma of the pancreas was quite unique in that she survived for 5 years despite the acute onset and rapid progression of the multiple liver metastases at least in part due to the long-lasting favorable response to octreotide and living-related liver transplantation.
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PMID:Octreotide-sensitive ectopic ACTH production by islet cell carcinoma with multiple liver metastases. 1280 33

A 24-year-old obese woman was found dead in her boyfriend's apartment in his absence. She had been admitted to the hospital six times previously because of diminished consciousness, respiratory failure, and pneumonia. A diagnosis of obesity-sleep apnea (Pickwickian) syndrome was made. An autopsy showed that she had an extremely small larynx, intra-alveolar hemorrhage, edema, pulmonary lymphocyte infiltration, and severe focal myocardial fibrosis. No fresh myocardial lesion, coronary arterial lesion, or findings of heart failure were seen. The woman's elder sister had also died of the same disease at the age of 23. The cause of death was diagnosed as respiratory failure and pneumonia with the sleep-apnea syndrome as the underlying cause of death. Although no autopsy reports of the sleep-apnea syndrome have been published in the field of forensic pathology, this syndrome is a predominant cause of sudden death in obese persons and could be a hidden cause of accidental death in such persons.
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PMID:Obesity-sleep apnea (Pickwickian) syndrome: autopsy findings and a medicolegal review. 1293 64

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections. This analysis assessed garenoxacin population pharmacokinetics and exposure-response relationships for safety (adverse effects [AE]) and antimicrobial activity (clinical cure and bacteriologic eradication of Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Data were obtained from three phase II clinical trials of garenoxacin administered orally as 400 mg once daily for 5 to 10 days for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, and sinusitis. Samples were taken from each patient before drug administration, 2 h following administration of the first dose, and on the day 3 to 5 visit. Individual Bayesian estimates of the fu (fraction unbound), the Cmax, and the fu for the area under the concentration-time curve from 0 to 24 h (fu AUC(0-24)) were calculated as measurements of drug exposure by using an ex vivo assessment of average protein binding. Regression analysis was performed to examine the following relationships: treatment-emergent AE incidence and AUC(0-24), Cmax, or patient factors; clinical response or bacterial eradication and drug exposure (fu Cmax/MIC, fu AUC(0-24)/MIC, and other exposure covariates); or disease and patient factors. Garenoxacin pharmacokinetics were described by a one-compartment model with first-order absorption and elimination. Clearance was dependent on creatinine clearance, ideal body weight, age, obesity, and concomitant use of pseudoephedrine. The volume of distribution was dependent on weight and gender. Patients with mild or moderate renal dysfunction had, on average, approximately a 16 or 26% decrease in clearance, respectively, compared to patients of the same gender and obesity classification with normal renal function. AE occurrence was not related to garenoxacin exposure. Overall, clinical cure and bacterial eradication rates were 91 and 90%, respectively, for S. pneumoniae and 93 and 92%, respectively, for the grouping of H. influenzae, H. parainfluenzae, and M. catarrhalis. The fu AUC(0-24)/MIC ratios were high (>90% were >200), and none of the pharmacokinetic-pharmacodynamic exposure measurements indexed to the MIC or other factors were significant predictors of clinical or bacteriologic response. Garenoxacin clearance was primarily related to creatinine clearance and ideal body weight. Although garenoxacin exposure was approximately 25% higher for patients with moderate renal dysfunction, this increase does not appear to be clinically significant as exposures in this patient population were not significant predictors of AE occurrence. Garenoxacin exposures were at the upper end of the exposure-response curves for measurements of antimicrobial activity, suggesting that 400 mg of garenoxacin once daily is a safe and adequate dose for the treatment of the specified community-acquired respiratory tract infections.
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PMID:Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections. 1556 55

We report a case of hepatocellular carcinoma (HCC) arising in nonalcoholic steatohepatitis (NASH). The patient, a 64-year-old man, was incidentally found to have multiple tumors in the liver when admitted for pneumonia. He had been obese, had been receiving a standard dose of valproic acid since clipping surgery for subarachnoid hemorrhage 17 years previously, and had not consumed any alcohol since the surgery. Laboratory data revealed moderate hyperlipidemia and no evidence of diabetes mellitus, hepatitis B or C infection. The patient died of hepatic insufficiency, and an autopsy was performed. A tumor, a maximum of 13 cm in diameter, grossly occupied the entire left lobe and one third of the right lobe of the liver. Histologically, moderately differentiated HCC was found with foci of poorly differentiated HCC. The non-tumorous area showed NASH with moderate bridging fibrosis, without interface hepatitis, hemochromatosis, or copper accumulation. In this patient, obesity, hyperlipidemia, and long-term treatment with valproic acid could have all been associated with induction of NASH. The present case suggests that HCC could develop in non-cirrhotic NASH liver, and that chronic inflammation in itself could be an important risk factor in the development of HCC.
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PMID:Hepatocellular carcinoma and nonalcoholic steatohepatitis developing during long-term administration of valproic acid. 1613 66

Living donor liver transplantation evolved in response to donor shortage. Current guidelines recommend potential living donors (LD) have a body mass index (BMI) <30. With the current obesity epidemic, locating nonobese LD is difficult. From September 1999 to August 2003, 68 LD with normal liver function test (LFTs) and without significant comorbidities underwent donor hepatectomy at our center. Post-operative complications were collected, including wound infection, pneumonia, hernia, fever, ileus, biliary leak, biliary stricture, thrombosis, bleeding, hepatic dysfunction, thrombocytopenia, deep venous thrombosis, pulmonary embolism, difficult to control pain, depression and anxiety. Complication rates for LD with BMI >30 (n = 16) and BMI <30 (n = 52) were compared. The incidence of wound infection increased with BMI, 4% for nonobese and 25% for obese LD (p = 0.024). There were no statistically significant differences for all other complications. No LD died. Recipient survival was 100% with obese LD and 80% with nonobese LD (p = 0.1). Select donors with a BMI >30 may undergo donor hepatectomy with acceptable morbidity and excellent recipient results. Updating current guidelines to include select LD with BMI >30 has the potential to safely increase the donor pool.
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PMID:Select utilization of obese donors in living donor liver transplantation: implications for the donor pool. 1630 13

The use of pulmonary artery catheters is under debate yet again. We look at two recent trials evaluating their impact on mortality. Our suspicions regarding obesity are proven and we also look at a simple, cost effective method of reducing ventilator-associated pneumonia. Finally, an intervention to improve the poor outcome associated with out-of hospital cardiac arrests is evaluated.
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PMID:Recently published papers: dying Swans and other stories. 1687 35

Fifty years ago, American Indian and Alaska Native children faced an overwhelming burden of disease, especially infectious diseases such as pneumonia, meningitis, tuberculosis, hepatitis A and B, and gastrointestinal disease. Death rates of American Indian/Alaska Native infants between 1 month and 1 year were much higher than in the US population as a whole, largely because of these infectious diseases. The health care of American Indian/Alaska Native patients was transferred to the Department of Health, Education, and Welfare in 1955 and placed under the administration of an agency soon to be known as the Indian Health Service. The few early pediatricians in the Indian Health Service recognized the severity of the challenges facing American Indian/Alaska Native children and asked for help. The American Academy of Pediatrics responded by creating the Committee on Indian Health in 1965. In 1986 the Committee on Native American Child Health replaced the Committee on Indian Health. Through the involved activity of these committees, the American Academy of Pediatrics participated in and influenced Indian Health Service policies and services and, combined with improved transportation, sanitation, and access to vaccines and direct services, led to vast improvements in the health of American Indian/Alaska Native children. In 1965, American Indian/Alaska Native postneonatal mortality was more than 3 times that of the general population of the United States. It is still more than twice as high as in other races but has decreased 89% since 1965. Infectious diseases, which caused almost one fourth of all American Indian/Alaska Native child deaths in 1965, now cause <1%. The Indian Health Service and tribal health programs, authorized by the Indian Self-Determination and Education Assistance Act of 1976 (Pub L. 93-638), continue to seek American Academy of Pediatrics review and assistance through the Committee on Native American Child Health to find and implement interventions for emerging child health problems related to pervasive poverty of many American Indian/Alaska Native communities. Acute infectious diseases that once were responsible for excess morbidity and mortality now are replaced by excess rates resulting from harmful behaviors, substance use, obesity, and injuries (unintentional and intentional). Through strong working partnerships such as that of the American Academy of Pediatrics and the Indian Health Service, progress hopefully will occur to address this "new morbidity." In this article we document the history of the Indian Health Service and the American Academy of Pediatrics committees that have worked with it and present certain statistics related to American Indian/Alaska Native child health that show the severity of the health-status disparities challenging American Indian/Alaska Native children and youth.
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PMID:Forty years in partnership: the American Academy of Pediatrics and the Indian Health Service. 1701 14


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