The systemic deletion of interleukin-1α reduces myocardial inflammation and attenuates ventricular remodeling in murine myocardial infarction.

Myocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1ß or the IL-1 receptor. In contrast, the potential role of IL-1α in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1α may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1α deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1α deficiency (IL-1α KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1α therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation.

Application of Finite Element Analysis (FEA) for the simulation of release of additives from multilayer polymeric packaging structures.

Computer programmes are available to predict, for consumer protection purposes, the migration of additives from a polymeric package during its contact with food. However most of these programs were developed to estimate migration only from single layer polymeric packaging under isothermal conditions. In this work a diffusion model was developed to simulate the migration from multilayer packaging and under non-isothermal temperature conditions, too. Finite Element Analysis (FEA) is used as a numerical approximation method to solve the diffusion equations describing such processes. The possibilities and limitations of the FEA method are presented and the correlation between experimental and computed results is discussed.

Pulmonary hypoplasia in the myogenin null mouse embryo.

Although fetal breathing movements are required for normal lung development, there is uncertainty concerning the specific effect of absent fetal breathing movements on pulmonary cell maturation. We set out to evaluate pulmonary development in a genetically defined mouse model, the myogenin null mouse, in which there is a lack of normal skeletal muscle fibers and thus skeletal muscle movements are absent in utero. Significant decreases were observed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E17, and E20. Reverse transcriptase/polymerase chain reaction, in situ immunofluorescence, and electron microscopy revealed early lung cell differentiation in both null and wild-type lungs as early as E14. However at E14, myogenin null lungs had decreased 5'-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were detected in the myogenin null mice but not in the wild-type littermates. These observations highlight the importance of skeletal muscle contractile activity in utero for normal lung organogenesis. Null mice lacking the muscle-specific transcription factor myogenin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.

Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies.

The myogenin gene encodes an evolutionarily conserved basic helix-loop-helix transcription (bHLH) factor that is required for differentiation of skeletal muscle, and its homozygous deletion in mice results in perinatal death from respiratory failure due to the lack of muscle fibers. Since the histology of skeletal muscle in myogenin null mice is reminiscent of that found in severe congenital myopathy patients, many of whom also die of respiratory complications, we sought to test the hypothesis that an aberrant human myogenin (myf4) coding region could be associated with some congenital myopathy conditions. With PCR amplification, we found similarly sized PCR products for the three exons of the myogenin gene in DNA from 37 patient and 40 control individuals. In contrast to previously reported sequencing of human myogenin (myf4), we describe with automated sequencing several base differences in flanking and coding regions plus an additional 659 and 498 bp in the first and second introns, respectively, in all 37 patient and 40 control samples. We also find a variable length (CA)-dinucleotide repeat in the second intron, which may have utility as a marker for future linkage studies. In summary, no causative mutations were detected in the myogenin coding locus of genomic DNA from 37 patients with severe congenital myopathy.

Adult smokers who do not smoke daily.

Almost 20% of Californian smokers do not smoke daily. Although occasional (non-daily) smoking occurs during uptake, a stable pattern of occasional smoking may imply a milder level of nicotine addiction. We use a longitudinal population sample of smokers interviewed in both 1990 and 1992 to evaluate the stability of occasional smoking. Further, we use 1992 data, including smokers only interviewed in 1992, to compare occasional smokers who have (ever-daily) and have not (never-daily) smoked daily for at least 6 months, and contrast them to daily smokers for key variables associated with addiction. All our analyses exclude uptake smokers. Two-thirds of never-daily occasional smokers in 1992 also smoked occasionally in 1990, compared to only about 40% of ever-daily occasional smokers. Never-daily occasional smokers smoke less than ever-daily ones. They are more often under age 40 years, of Hispanic origin, and were more likely to begin regular smoking beyond their teen years. Demographically, ever-daily occasional smokers were similar to daily smokers except for being more educated. However, both ever-daily and never-daily smokers differed from daily smokers with respect to long-term quitting history, plans to quit, confidence they could quit, and belief they are addicted to cigarettes. Our findings suggest that occasional smoking can be a stable pattern for long periods. Occasional smokers, particularly never-daily ones, appear to be much less addicted to nicotine than daily smokers.

Low-cost cigarettes and smoking behavior in California, 1990-1993.

Low-cost generic cigarettes grew dramatically in market share between 1990 and 1993, raising concerns that some smokers might view generics as an alternative to quitting. We report sociodemographic predictors of generic brand choice among a cross-sectional sample of California smokers and investigate changes in brand choice in a longitudinal sample of California smokers between 1990 and 1992. We also focus on brand preferences among California adolescents. One third of smokers who switched cigarette brands between 1990 and 1992 switched to generics. Non-Hispanic whites, rural residents, and lower income smokers were twice as likely to buy generics as other smokers were. Heavy cigarette consumption was strongly associated with smoking generic cigarettes. Women appeared more price-sensitive in cigarette purchasing than men did, and generic brands were the most frequently purchased cigarettes for female smokers older than age 45. Generics were less popular among adolescents than among adults. Generic cigarettes provide a low-cost alternative to price-sensitive smokers, but further studies are needed to establish the role and influence of generic cigarettes on smoking prevalence and public health. Medical Subject Headings (MeSH): smoking, smoking cessation, adolescent behavior, women, prevalence.

Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review.

OBJECTIVE: Compare 5-year melanoma survival rates to rates in medical literature. DESIGN: Retrospective. SETTING: Hospital in Tijuana, Mexico. PATIENTS: White adult patients (N = 153) with superficial spreading and nodular melanoma, aged 25-72 years. INTERVENTION: Gerson's diet therapy: lactovegetarian; low sodium, fat and (temporarily) protein; high potassium, fluid, and nutrients (hourly raw vegetable/fruit juices). Metabolism increased by thyroid; calorie supply limited to 2600-3200 calories per day. Coffee enemas as needed for pain and appetite. MAIN OUTCOME MEASURE: 5-year survival rates by stage at admission. RESULTS: Of 14 patients with stages I and II (localized) melanoma, 100% survived for 5 years, compared with 79% of 15,798 reported by Balch. Of 17 with stage IIIA (regionally metastasized) melanoma, 82% were alive at 5 years, in contrast to 39% of 103 from Fachklinik Hornheide. Of 33 with combined stages IIIA + IIIB (regionally metastasized) melanoma, 70% lived 5 years, compared with 41% of 134 from Fachklinik Hornheide. We propose a new stage division: IVA (distant lymph, skin, and subcutaneous tissue metastases), and IVB (visceral metastases). Of 18 with stage IVA melanoma, 39% were alive at 5 years, compared with only 6% of 194 from the Eastern Cooperative Oncology Group. Survival impact was not assessed for stage IVB. Male and female survival rates were identical for stages I-IIIB, but stage IVA women had a strong survival advantage. CONCLUSIONS: The 5-year survival rates reported here are considerably higher than those reported elsewhere. Stage IIIA/B males had exceptionally high survival rates compared with those reported by other centers.

Estimates of population smoking prevalence: self-vs proxy reports of smoking status.

OBJECTIVES: In the face of rising costs of surveillance systems, it is time to reexamine the feasibility of including proxy respondents in surveys designed to provide population estimates of smoking prevalence. METHODS: Data are from the California. Tobacco Surveys, which are random-digit dialed telephone surveys. One adult provided demographic information and smoking status for all household residents. Additionally, some adults were selected for in-depth interviews that also included smoking status questions. We matched information from proxy respondents and self-respondents and evaluated smoking status discrepancies between them relative to demographic and other factors (n = 2930 matched pairs) in 1992. We address the potential bias these discrepancies might introduce into the population estimate of smoking prevalence. RESULTS: Overall, the discrepancy between proxy report and self-report was 4.3%, and it increased particularly when the self-respondent reported nondaily smoking or recent quitting. Discrepancies acted in both directions, and the net bias was that the screener survey overestimated smoking prevalence by 0.1% in 1992 (0.3% in 1990). CONCLUSIONS: Smoking status questions can be added to ongoing surveys such as the census or labor force surveys; one adult could provide smoking status for all household members.

Coronary artery bypass operation in septuagenarians.

Increasing numbers of patients more than 70 years old are at risk from coronary artery disease. The continued success of coronary artery bypass operation in selected patients provides impetus for applying this procedure to older patients as well. Our results indicate coronary artery operation is effective in older patients and has a low mortality (3% in our series). In patients in this age group, coronary artery operation can be combined with other procedures, when indicated, such as cardiac valve replacement or repair, left ventricular aneurysmectomy, carotid endarterectomy, and cholecystectomy.