Mycobacterium avium complex pulmonary disease in patients without HIV infection

Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-gamma pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal alpha(1)-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.     

Liver histology in ICU patients dying from sepsis：A clinico-pathological study

AIM：To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit.
METHODS： Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded.
RESULTS： Liver biochemistries were increased in the majority of patients before death. Histology of liver biopsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 （40%） patients and hepatitc in 9/15 （60%）. Steatosis was observed in 11/15 （73.3%） patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was associated with increased hospitalization in the ICU prior death （P = 0.026）.
CONCLUSION： Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.     

Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.

BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.     

Staging of portal hypertension and portosystemic shunts using dynamic nuclear medicine investigations

AIM： To explore portal hypertension and portosystemic shunts and to stage chronic liver disease （CLD） based on the pathophysiology of portal hemodynamics. METHODS： Per-rectal portal scintigraphy （PRPS） was performed on 312 patients with CLD and liver angioscintigraphy （LAS） on 231 of them. The control group included 25 healthy subjects. We developed a new model of PRPS interpretation by introducing two new parameters, the liver transit time （LTT） and the circu-lation time between right heart and liver （RHLT）. LTT for each lobe was used to evaluate the early portal hypertension. RHLT is useful in cirrhosis to detect liver areas missing portal inflow. We calculated the classical per-rectal portal shunt index （PRSI） at PRPS and the hepatic perfusion index （HPI） at LAS. RESULTS： The normal LTT value was 24 ± 1 s. Abnormal LTT had PPV = 100% for CLD. Twenty-seven noncirrhotic patients had LTT increased up to 35 s （median 27 s）. RHLT （42 ± 1 s） was not related to liver disease. Cirrhosis could be excluded in all patients with PRSI 〈 5% （P 〈 0.01）. PRSI 〉 30% had PPV = 100% for cirrhosis. Based on PRPS and LAS we propose the classification of CLD in 5 hemodynamic stages. Stage 0 is normal （LTT = 24 s, PRSI 〈 5%）. In stage 1, LTT is increased, while PRSI remains normal. In stage 2, LTT is decreased between 16 s and 23 s, whereas PRSI is increased between 5% and 10%. In stage 3, PRSI is increased to 10%-30%, and LTT becomes undetectable by PRPS due to the portosystemic shunts. Stage 4 includes the patients with PRSI 〉 30%. RHLT and HPI were used to subtype stage 4. In our study stage 0 had NPV = 100% for CLD, stage 1 had PPV = 100% for non-cirrhotic CLD, stages 2 and 3 represented the transition from chronic hepatitis to cirrhosis, stage 4 had PPV = 100% for cirrhosis. CONCLUSION： LTT allows the detection of early portal hypertension and of opening of transhepatic shunts. PRSI is useful in CLD with extrahepatic portosystemic shunts. Our hemodynamic model stag     

α1-antitrypsin deficiency in fraternal twins born with familial spontaneous pneumothorax

We report a case of spontaneous familial pneumothorax in fraternal twin boys. The twins' family history is remarkable for reactive airway disease and a female sibling also born with spontaneous pneumothorax. The family had no history of connective tissue disorders, renal cancer, or dermatologic diseases. Analysis of the twins' α(1)-antitrypsin (AAT) genotype, phenotype, and serum concentration revealed that both were compound heterozygous for rare SERPINA1 alleles. These findings suggest a role for AAT deficiency in spontaneous pneumothorax of the newborn. To our knowledge, these are the first genetic data to support etiology of neonatal spontaneous familial pneumothorax.