Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

ObjectiveThe objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).Patients and methodsWe studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV₁] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.ResultsThe mean (SD) age of patients was 69 (8) years and the mean FEV₁ was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.ConclusionsMortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.     

Chronic Alcohol Ingestion Enhances Tumor Necrosis Factor-α Expression and Salivary Gland Apoptosis

We investigated the extent of induction in sublingual salivary gland cells apoptosis and tumor necrosis factor-α (TNF-α) expression with chronic ethanol ingestion. The experiments were conducted on rats pair-fed for 8 weeks with alcohol-containing and control liquid diet. The animals were killed, their sublingual glands dissected, and the glandular tissue used for quantitization of TNF-α expression and the assays of acinar cells apoptosis employing sandwich enzyme immunoassay for histone-associated DNA fragments. The mean value for TNF-α in sublingual gland of the control group was 22.3 pg/mg of protein and showed a 1.6-fold increase in the chronic ethanol diet group to 36.5 pg/mg of protein. In comparison with the controls, the sublingual gland of the chronic ethanol diet group also exhibited a 3.4-fold enhancement in acinar cell apoptosis. These findings suggest that chronic ethanol ingestion causes the enhancement in TNF-α expression and leads to the induction in salivary gland acinar cells apoptosis. Thus, the diminished secretion of saliva in alcoholics may be a direct result of increased salivary gland apoptosis.     

Molecular epidemiologic studies of polycyclic aromatic hydrocarbon-DNA adducts and breast cancer

We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) controls. We conducted a case-control study utilizing two control groups: BBD controls who donated tissue and blood samples, and healthy controls who donated blood samples. In comparisons of tumor tissue from cases and benign tissue from BBD controls, increasing adduct levels were significantly associated with case-control status [odds ratio (OR) = 2.40, 95% confidence interval (CI) 1.18-4.92], whereas in comparisons of nontumor tissue from cases and benign tissue from BBD controls the association was nonsignificant (OR = 1.97, 95% CI 0.94-4.17). We also show among cases, but not among BBD controls, that the GSTM1 null genotype is associated with increased adduct levels in breast tissue. Our reliability study found the scoring procedures used with the immunohistochemical assay to have high reliability, 0.93 in nontumor, 0.82 in tumor, and 0.74 in benign tissues. However, we found that the technician significantly contributed to the total variability of a series of data. Finally, we did not find a consistent bias to the null associated with the use of BBD controls; however, BBD controls may overestimate the prevalence of family history of breast cancer compared to that of healthy controls (18% vs.14%). We hypothesize that the higher prevalence results from a referral bias and discuss how this may influence our results.     

Adaptation of Insulin Clearance to Metabolic Demand Is a Key Determinant of Glucose Tolerance

With the development of insulin resistance (IR), there is a compensatory increase in the plasma insulin response to offset the defect in insulin action to maintain normal glucose tolerance. The insulin response is the result of two factors: insulin secretion and metabolic clearance rate of insulin (MCR_I). Subjects (104 with normal glucose tolerance [NGT], 57 with impaired glucose tolerance [IGT], and 207 with type 2 diabetes mellitus [T2DM]), divided in nonobese and obese groups, received a euglycemic insulin-clamp (40 mU/m² ⋅ min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCR_I was calculated during the insulin-clamp performed with [3-³H]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production × fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid × FPI). MCR_I during the insulin clamp was reduced in obese versus nonobese NGT (0.60 ± 0.03 vs. 0.73 ± 0.02 L/min ⋅ m², P < 0.001), in nonobese IGT (0.62 ± 0.02, P < 0.004), and in nonobese T2DM (0.68 ± 0.02, P < 0.03). The MCR_I during the insulin clamp was strongly and inversely correlated with IR (r = −0.52, P < 0.0001). During the OGTT, the MCR_I was suppressed within 15–30 min in NGT and IGT subjects and remained suppressed. In contrast, suppression was minimal in T2DM. In conclusion, the development of IR in obese subjects is associated with a decline in MCR_I that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM.     

Long-term azithromycin use is not associated with QT prolongation in children with cystic fibrosis

Chronic Azithromycin (AZM) is a common treatment for lung infection. Among adults at risk of cardiac events, AZM use has been associated with cardiovascular harm. We assessed cardiovascular safety of AZM among children with CF, as a secondary analysis of a placebo-controlled, clinical trial, in which study drug was taken thrice-weekly for a planned 18 months. Safety assessments using electrocardiogram (ECG) occurred at study enrollment, and then after 3 weeks and 18 months of participation. Among 221 study participants with a median of 18 months follow-up, increased corrected QT interval (QTc) of ≥30 msec was rare, at 3.4 occurrences per 100 person-years; and incidence of QTc prolongation was no higher in the AZM arm than the placebo arm (1.8 versus 5.4 per 100 person-years). No persons experienced QTc intervals above 500 msec. Long-term chronic AZM use was not associated with increased QT prolongation.     

Pregnancy outcome of patients with pruritic urticarial papules and plaques of pregnancy.

OBJECTIVE: The study was designed to investigate obstetric risk factors and pregnancy outcome of patients with pruritic urticarial papules and plaques of pregnancy (PUPPP). METHODS: A population-based study comparing all pregnancies of women with and without PUPPP was conducted. Deliveries occurred during the years 1988-2002 at the Soroka University Medical Center. A multivariable logistic regression model was constructed in order to find independent risk factors associated with PUPPP. RESULTS: During a 15-year period, 159 197 deliveries took place. PUPPP complicated 42 (0.03%) of all pregnancies. Using a multivariable analysis, the following conditions were significantly associated with PUPPP: multiple pregnancies (odds ratio (OR) = 4.9, 95% confidence interval (CI) 1.7-14.1), hypertensive disorders (OR = 2.2, 95% CI 1.1-4.7), and induction of labor (OR = 7.6, 95% CI 4.0-14.5). Higher rates of 5-minute Apgar scores lower than 7 (OR = 8.0, 95% CI 4.4-14.9) and of cesarean deliveries (OR = 2.9, 95% CI 1.5-5.6) were noted in the PUPPP as compared to the comparison group. While investigating other perinatal outcome parameters such as oligohydramnios, intrauterine growth restriction, meconium-stained amniotic fluid and perinatal mortality, no significant differences were observed between the groups. CONCLUSION: Pruritic urticarial papules and plaques of pregnancy is a condition significantly associated with multiple pregnancies, hypertensive disorders, and induction of labor. Perinatal outcome is comparable to pregnancies without PUPPP.     

Shoulder dystocia: a comparison of patients with and without diabetes mellitus

Background: The study was aimed to compare pregnancies complicated with shoulder dystocia, of patients with and without diabetes mellitus. Methods: A comparison of all singleton, vertex, term deliveries between the years 1988–1999, complicated with shoulder dystocia with and without diabetes mellitus was performed. Statistical analysis was done using receiver operating characteristic curve analysis. Results: Using a receiver operating characteristic curve analysis, the area under the curve for birth weight was 0.92 (95% CI 0.90–0.93). However, for birth weight of 4,000 g the sensitivity was only 56% with specificity of 95%. While comparing shoulder dystocia between patients with (n=38) and without diabetes mellitus (n=207), neonates of the diabetic patients were significantly heavier (mean birth weight 4,244.2±515.1 vs. 4,051.6±389.5; P=0.008) and had higher rate of Apgar scores lower than 7 at 1 min (50.0% vs. 25.9%; P=0.030), but not at 5 min (2.6% vs. 2.0%; P=0.083) when compared to the non-diabetic group. No significant differences were noted regarding perinatal mortality between the groups (0% vs. 4.3%; P=0.362). Conclusions: The newborn of the diabetic mother complicated with shoulder dystocia does not appear to be at an increased risk for perinatal morbidity compared with the newborn of the non-diabetic mother. Presented in part at the Society for Gynecologic Investigation 50th Annual Scientific Meeting, Washington, DC, 27–30 March 2003.     

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.     

Carrier frequency of autosomal-recessive disorders in the Ashkenazi Jewish population: should the rationale for mutation choice for screening be reevaluated?

BACKGROUND: Ashkenazi Jewish (AJ) population is at increased risk for several recessive inherited diseases. Therefore, carrier testing of AJ members is important in order to identify couples at risk of having offspring with an autosomal recessive disorder. METHODS: In the present study, a database containing the results of 28 410 genotyping assays was screened. Ten thousand seventy eight nonselected healthy members of the AJ population were tested for carrier status for the following diseases; Gaucher disease (GD), cystic fibrosis (CF), Familial dysautonomia (FD), Alpha 1 antitrypsin (A1AT), Mucolipidosis type 4 (ML4), Fanconi anemia type C (FAC), Canavan disease (CD), Neimann-Pick type 4 (NP) and Bloom syndrome (BLM). RESULTS: The results demonstrated that 635 members were carriers of one mutation and 30 members were found to be carriers of two mutations in the different genes related to the development of the above mentioned diseases. GD was found to have the highest carrier frequency (1:17) followed by CF (1:23), FD (1:29), A1AT (1:65), ML4 (1:67) and FAC (1:77). The carrier frequency of CD, NP and BLM was 1:82, 1:103 and 1:157, respectively. CONCLUSIONS: The frequency of the disease-causing mutations screened routinely among the AJ population indicated that there are rare mutations with very low frequencies. The screening policy of the disease-causing mutations should be reevaluated and mutations with a high frequency should be screened, while rare mutations with a lower frequency may be tested in partners of carriers.