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Individuals with severe alpha-1-antitrypsin (alpha1AT) deficiency (phenotype Pi ZZ) are abnormally liable to develop emphysema, but it is uncertain whether those with partial alpha1AT deficiency (phenotypes Pi MS and MZ) are similarly susceptible. This study was undertaken to determine the frequency of the various Pi phenotypes in a working population in Northern Ireland and to compare the performance of simple pulmonary function tests and prevalence of respiratory symptoms and chest illness between different phenotypes. The population sample consisted of 1995 working men and women aged between 35 and 70 years. The MRC Questionnaire (1966) was used to assess respiratory symptoms, a forced expiratory spirogram was recorded, and a blood sample was analysed for alpha1AT phenotype by acid starch gel electrophoresis and antigen-antibody crossed electrophoresis in every case. The percentage frequencies of the alpha1AT phenotypes were: Pi MM 86-5; MS 7-97; MZ 3-86; IM 0-6; FM 0-4; SZ 0-25; M 0-15; SS 0-1; Z 0-05; MP 0-05; FS 0-05. Respiratory symptoms and a history of previous chest illness occurred with similar frequency among the Pi M, MS, and MZ phenotypes, and a comparison of the regression coefficients for FEV1, FVC, and MMF on age for each phenotype group showed no significant differences between them overall, or when subdivided according to smoking habits or dust exposure. These findings provide no evidence that individuals of phenotype Pi MS or MZ are more than usually liable to develop chronic airways obstruction.
Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the main precursor of lactate and lactate is reconverted into glucose by the Cori cycle. Literature relevant to the underlying mechanism of combined deep hypoglycaemia and severe hyperlactataemia was assessed. We also assessed the literature for evidence of protection against deep hypoglycaemia by hyperlactataemia. Four syndromes demonstrating hypoglycaemia+hyperlactataemia were found: 1) paracetamol-induced acute liver failure, 2) severe malaria, 3) lymphoma and 4) glucose-6-phosphatase deficiency. An impaired Cori cycle is a key component in all of these metabolic states. Apparently the liver, after exhausting its glycogen stores, loses the gluconeogenic pathway to generate glucose and thereby its ability to remove lactate as well. Several patients with lactic acidosis and glucose levels below 1.7 mmol/l who were not in a coma have been reported. These observations and other data coherently indicate that lactate-protected hypoglycaemia is, at least transiently, a viable state under experimental and clinical conditions. Severe hypoglycaemia+hyperlactataemia reflects failure of the gluconeogenic pathway of lactate metabolism. The existence of lactate-protected hypoglycaemia implies that patients who present with this metabolic state should not automatically be considered to have sustained irreversible brain damage. Moreover, therapies that aim to achieve hypoglycaemia might be feasible with concomitant hyperlactataemia.
ABSTRACT Organisms within the Mycobacterium avium complex (MAC) may have differential virulence. We compared 33 subjects with MAC pulmonary disease to 75 subjects with a single positive culture without disease. M. avium isolates were significantly more likely to be associated with MAC pulmonary disease (odds ratio = 5.14, 95% confidence interval = 1.25 to 22.73) than M. intracellulare .
Prediction models that identify populations at risk for high health expenditures can guide the management and allocation of financial resources.To compare the ability for identifying individuals at risk for high health expenditures between the single-item assessment of general self-rated health (GSRH), "In general, would you say your health is Excellent, Very Good, Good, Fair, or Poor?," and 3 more complex measures.We used data from a prospective cohort, representative of the US civilian noninstitutionalized population, to compare the predictive ability of GSRH to: (1) the Short Form-12, (2) the Seattle Index of Comorbidity, and (3) the Diagnostic Cost-Related Groups/Hierarchal Condition Categories Relative-Risk Score. The outcomes were total, pharmacy, and office-based annualized expenditures in the top quintile, decile, and fifth percentile and any inpatient expenditures.Medical Expenditure Panel Survey panels 8 (2003-2004, n = 7948) and 9 (2004-2005, n = 7921).The GSRH model predicted the top quintile of expenditures, as well as the SF-12, Seattle Index of Comorbidity, though not as well as the Diagnostic Cost-Related Groups/Hierarchal Condition Categories Relative-Risk Score: total expenditures [area under the curve (AUC): 0.79, 0.80, 0.74, and 0.84, respectively], pharmacy expenditures (AUC: 0.83, 0.83, 0.76, and 0.87, respectively), and office-based expenditures (AUC: 0.73, 0.74, 0.68, and 0.78, respectively), as well as any hospital inpatient expenditures (AUC: 0.74, 0.76, 0.72, and 0.78, respectively). Results were similar for the decile and fifth percentile expenditure cut-points.A simple model of GSRH and age robustly stratifies populations and predicts future health expenditures generally as well as more complex models.
