Familial components of the multiple metabolic syndrome: the ARIC Study

Summary The association of a parental history of diabetes mellitus and hypertension with the multiple metabolic syndrome (MMS) was studied in a population survey of middle-aged adults. The eligible population was drawn from the baseline examination of the Atherosclerosis Risk in Communities Study, a population-based, bi-ethnic, multi-centre cohort study. The MMS was defined as a multivariate, categorical phenotype of co-occurring diabetes, hypertension, and dyslipidaemia. MMS cases (n = 356) were compared to disorder-free control subjects (n = 6797) with respect to their parental history of diabetes and hypertension. MMS cases were more likely to report a history of diabetes in both parents (odds ratio [OR] 4.7, 95 % confidence interval (CI) 1.5–14.7) or a history of hypertension in both parents (OR 1.9, 95 % CI 1.1–3.0) than control subjects, adjusting for BMI, waist-to-hip ratio, age, gender, and ethnicity/centre. A parental history of diabetes and hypertension in both parents was associated with the greatest increase in odds of MMS (OR 8.3, 95 % CI 3.0–22.8). A dose-response relationship between the number of parental disorders (one; two; three to four) and the odds of MMS was observed (OR 1.2, 95 % CI 0.9–1.7; OR 2.0, 95 % CI 1.4–2.8; OR 4.0, 95 % CI 2.5–6.2). Based on the marked associations observed between a parental history of MMS components and the clustering of these metabolic disorders in the offspring generation, we conclude that genetic and/or non-genetic familial influences play a role in the development of the multiple metabolic syndrome. [Diabetologia (1997) 40: 963–970] Received: 20 February 1997 and in revised form: 2 May 1997     

Intern candidates who withdraw from contracts

Objective: To study the prevalence of intern candidates accepted through the National Resident Matching Program (NRMP) or after the match who subsequently withdraw and the attitudes of program directors regarding this issue. Design: Mailed survey. Setting: Four hundred fifty-four internal medicine program directors. Measurements: Questionnaires assessing program directors’ attitudes toward interns who contract for positions after having verbal or written agreements elsewhere (and the program directors who accept them), the importance of this problem, and the incidence of this problem. Main results: Fifty-five programs (of the 221 responding) experienced intern withdrawals. Programs with larger numbers of open positions after the match had more intern withdrawals (p=0.03). Eleven of the program directors knew of the prior commitment of the intern, and in all cases the other program director was called for permission to accept the intern. Program directors had negative feelings about both the interns who withdrew and the program directors who accepted them. Community, municipal, and Veterans Affairs hospital program directors were significantly less negative than those in university and university-affiliated hospitals toward interns who withdrew from written commitments (p=0.001) and the program directors who accepted them (p<0.05). Conclusion: Problems with intern candidate withdrawals from offered/matched programs affect a significant proportion of programs, especially those with larger numbers of unmatched positions. Program directors are generally disapproving.     

Avian sarcoma virus 17 carries the jun oncogene.

Biologically active molecular clones of avian sarcoma virus 17 (ASV 17) contain a replication-defective proviral genome of 3.5 kilobases (kb). The genome retains partial gag and env sequences, which flank a cell-derived putative oncogene of 0.93 kb, termed jun. The jun gene lacks preserved coding domains of tyrosine-specific protein kinases. It also shows no significant nucleic acid homology with other known oncogenes. The probable transformation-specific protein in ASV 17-transformed cells is a 55-kDa gag-jun fusion product.     

Experimental polymyxin B-induced interstitial lung disease characterized by an accumulation of cytotoxic eosinophils in the alveolar structures

A variety of lung disorders are associated with the accumulation of eosinophils in the alveolar structures. To help understand the role of eosinophils in these disorders, an animal model of eosinophilic lung disease was developed. Administration of an aerosol of polymyxin B to guinea pigs (3 times per wk for 4 wk) produced diffuse interstitial lung disease with alveolar wall thickening and an alveolitis characterized by marked increases in eosinophils and alveolar macrophages. Bronchoalveolar lavage confirmed the presence of significantly increased numbers of eosinophils and alveolar macrophages in polymyxin-B-treated animals compared with those in control animals. Using density gradient centrifugation, approximately 10(7) eosinophils could be purified from the lungs of a single polymyxin-B-treated animal. Importantly, eosinophils purified from the lungs from polymyxin B-treated animals exhibited significant spontaneous cellular cytotoxicity for human fetal lung fibroblasts. In contrast, neither eosinophils from control animals nor alveolar macrophages from either group of animals were cytotoxic. These findings demonstrate that eosinophils possess effector processes capable of injuring the lung parenchyma and suggest that eosinophils can contribute to the pathogenesis of the interstitial lung disease.     

Long-term trends in the use of complementary and alternative medical therapies in the United States

BACKGROUND: Although recent research has shown that many people in the United States use complementary and alternative medical (CAM) therapies, little is known about time trends in use. OBJECTIVE: To present data on time trends in CAM therapy use in the United States over the past half-century. DESIGN: Nationally representative telephone survey of 2055 respondents that obtained information on current use, lifetime use, and age at first use for 20 CAM therapies. SETTING: The 48 contiguous U.S. states. PARTICIPANTS: Household residents 18 years of age and older. MEASUREMENT: Retrospective self-reports of age at first use for each of 20 CAM therapies. RESULTS: Previously reported analyses of these data showed that more than one third of the U.S. population was currently using CAM therapy in the year of the interview (1997). Subsequent analyses of lifetime use and age at onset showed that 67.6% of respondents had used at least one CAM therapy in their lifetime. Lifetime use steadily increased with age across three age cohorts: Approximately 3 of every 10 respondents in the pre-baby boom cohort, 5 of 10 in the baby boom cohort, and 7 of 10 in the post-baby boom cohort reported using some type of CAM therapy by age 33 years. Of respondents who ever used a CAM therapy, nearly half continued to use many years later. A wide range of individual CAM therapies increased in use over time, and the growth was similar across all major sociodemographic sectors of the study sample. CONCLUSIONS: Use of CAM therapies by a large proportion of the study sample is the result of a secular trend that began at least a half century ago. This trend suggests a continuing demand for CAM therapies that will affect health care delivery for the foreseeable future.     

Dependence of enhanced maximal exercise performance on increased peak skeletal muscle perfusion during long-term captopril therapy in heart failure

Maximal oxygen uptake (VO2), skeletal muscle blood flow by xenon-133 washout technique and femoral vein arteriovenous oxygen difference and lactate were measured at rest and during maximal bicycle exercise in eight patients with severe congestive heart failure before and after 8 weeks of therapy with captopril. During therapy, skeletal muscle blood flow at rest increased significantly from 1.5 +/- 0.6 to 2.6 +/- 1.0 ml/100 g per min (p less than 0.05), with a concomitant decrease in the femoral arteriovenous oxygen difference from 10.0 +/- 1.7 to 8.3 +/- 1.9 ml/100 ml (p less than 0.05). Maximal VO2 increased significantly from 13.4 +/- 3.0 to 15.5 +/- 4.1 ml/kg per min (p less than 0.05). In four patients, the increase in maximal VO2 averaged 3.7 ml/kg per min (range 2.7 to 4.9), whereas in the remaining four patients, it was less than 1 ml/kg per min. Overall, peak skeletal muscle blood flow attained during exercise did not change significantly during long-term therapy with captopril (19.6 +/- 6.2 versus 27.6 +/- 14.3 ml/100 g per min, p = NS). However, the four patients with a significant increase in maximal VO2 experienced substantial increases in peak skeletal muscle blood flow and the latter changes were linearly correlated with changes in maximal VO2 (r = 0.95, p less than 0.001). Femoral arteriovenous oxygen difference at peak exercise was unchanged (12.6 +/- 2.6 versus 12.6 +/- 2.4 ml/100 ml). Thus, improvement in maximal VO2 produced by long-term therapy with captopril is associated with an increased peripheral vasodilatory response to exercise, and this improvement only occurs when the peak blood flow is augmented.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hybridization of RNA to double-stranded DNA: formation of R-loops.

RNA can hybridize to double-stranded DNA in the presence of 70% formamide by displacing the identical DNA strand. The resulting structure, called an R-loop, is formed in formamide probably because of the greater thermodynamic stability of the RNA-DNA hybrid when it is near the denaturation temperature of duplex DNA. The rate of R-loop formation is maximal at the temperature at which half of the duplex DNA is irreversibly converted to single-stranded DNA (the strand separation temperature of tss) of the duplex DNA and falls precipitously a few degrees above or below that temperature. This maximal rate is similar to the rate of hybridization of RNA to single-stranded DNA under the same conditions. At temperatures above the tss the rate is proportional to the RNA concentration. However, at temperatures below tss the rate of R-loop formation is less dependent upon the RNA concentration. Once formed, the R-loops display considerable stability; the formamide can be removed and the DNA can be cleaved with restriction endonucleases without loss of R-loop structures.     

Influenza defective interfering viral RNA is formed by internal deletion of genomic RNA.

The 3'- and 5'-terminal nucleotide sequences of the defective interfering (DI) RNAs present in a preparation of DI influenza virus were determined. It was found that all DI RNAs possessed identical terminal sequences for at least the first 13 nucleotides at the 5' end and at least the last 12 nucleotides at the 3' end. The sequence of the DI RNAs is (5')A-G-U-A-G-A-A-A-C-A-A-G-G-...-C-C-U-G-C-U-U-U-C-G-C-U-OH(3'). In addition, the same sequences were present at the 3' and 5' termini of the viral polymerase genes (P1, P2, and P3) from which these DI RNAs originate. These results indicate that DI RNAs of influenzing virus are formed by an internal deletion of the genomic RNA.     

Chronic intravascular hemolysis after aortic valve replacement with Ionescu-Shiley xenograft: Comparative study with Bjork-Shiley prosthesis

Twenty patients with a prosthetic valve (Ionescu-Shiley or Bjork-Shiley) in the aortic position were studied for evidence of intravascular hemolysis. Serum lactic dehydrogenase and serum haptoglobin levels were used as the most sensitive indicators of hemolysis. Elevated concentrations of lactic dehydrogenase were found in all 10 patients with an Ionescu-Shiley prosthesis (mean 402 IU/liter) and in 7 of 10 patients with a Bjork-Shiley prosthesis (mean 234 IU/liter). The mean serum haptoglobin was 15 mg/dl (range 10 to 28) in patients with the Ionescu-Shiley valve and 96 mg/dl (15 to 284) for those with the Bjork-Shiley valve. This study indicates the presence of chronic intravascular hemolysis in patients with the Ionescu-Shiley aortic valve. The increase in lactic dehydrogenase was significantly greater in patients with the Ionescu-Shiley prosthesis than in those with the Bjork-Shiley prosthesis, indicating a slightly shorter red cell life span in the former group.     

Low sweat electrolytes in a patient with cystic fibrosis

A patient with the clinical syndrome of cystic fibrosis characterized by chronic pulmonary disease, infection with mucoid Pseudomonas aeruginosa, sinusitis, nasal polyposis, abnormal pancreatic bicarbonate response to secretin stimulation, but normal levels of trypsin and chymotrypsin in the duodenal drainage, and a sibling with autopsy-documented cystic fibrosis, is described. Sweat chloride ranged from 20 to 44 meq/liter and sweat sodium from 36 to 55 meq/liter. Immunoglobulin deficiency, α₁-antitrypsin deficiency, tuberculosis and abnormalities of ciliary ultrastructure were excluded. Review of sweat electrolytes in 213 patients with cystic fibrosis revealed that patients with normal pancreatic enzyme release have significantly lower sweat sodium and chloride concentrations (p <0.0005) than do patients with pancreatic insufficiency.Chronic pulmonary disease, pancreatic insufficiency and elevated levels of sweat electrolytes comprise the classic diagnostic triad for cystic fibrosis. The expression of these features may be variable, but the sweat test remains the cardinal laboratory confirmation of the diagnosis. Over 98 percent of patients with cystic fibrosis have sweat chloride values greater than 60 meq/liter, 1 to 2 percent between 50 and 60 meq/liter, and only about one in 1,000, like our patient, less than 50 meq/liter. Patients with cystic fibrosis with borderline sweat chloride values frequently have chronic pulmonary disease but intact pancreatic enzyme release. In such patients, family history, ancillary clinical features and systematic exclusion of other syndromes assume special diagnostic importance.