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PubMed2006

Postmortem molecular screening for cardiac ryanodine receptor type 2 mutations in sudden unexplained death: R420W mutated case with characteristics of status thymico-lymphatics.

BACKGROUND: Mutations of the cardiac ryanodine receptor type 2 (RyR2) gene are known to cause effort-induced polymorphic ventricular arrhythmia, syncope and sudden death. METHODS AND RESULTS: The possible mutations in the RyR2 gene were examined in 18 autopsy cases of sudden unexplained death (SUD). Two cases were found to have the heterozygous missense mutation in exon 14 (nucleotide change C1258T, coding effect R420W). Both cases showed mild fatty infiltration of the right ventricular apex. Interestingly, 1 case showed an enlarged thymus with accompanying hypertrophy of the tonsils and mesenteric lymph nodes. In addition, a narrowing of the aorta was observed in this case. These phenotypic characteristics are consistent with status thymico-lymphaticus, which combines sudden death with an enlargement of lymphoid organs and hypoplasia of the cardiovascular system. The second case also displayed some characteristics of status thymico-lymphaticus. CONCLUSION: The R420W mutation has already been reported in families with juvenile sudden death and may be causative of sudden death in our cases. Postmortem molecular screening of the RyR2 gene could be useful for investigation for cause of death in SUD. The possible association of the RyR2 mutation with status thymico-lymphaticus is discussed.

Adolescent↗
PubMed1983

A reappraisal of time trends in ulcer disease: factors related to changes in ulcer hospitalization and mortality rates.

There has been a dramatic decline in reported hospitalization and mortality rates for peptic ulcer disease in the past two decades. Data from the National Center for Health Statistics and from the Commission on Professional and Hospital Activities were examined to determine the cause(s) for this decline. Gastric and duodenal ulcer mortality rates decreased by 58 per cent and 68 per cent, respectively, from 1962 to 1978; changes in criteria for selecting the underlying cause of death might account for some of this apparent decrease. Hospitalization rates for duodenal ulcers decreased nearly 50 per cent from 1970 to 1978, but hospitalizations for gastric ulcers did not decrease. During this same time period, hospitalizations for peptic ulcers as one of the "all listed" causes remained stable, and hospitalizations for a closely related diagnosis, gastritis/duodenitis, increased. Changes in coding practices, hospitalization criteria, and diagnostic procedures appear to have contributed to the decline in reported hospitalization and mortality rates for peptic ulcer disease.

Hospitalization↗
PubMed2006

A novel nuclear-encoded mitochondrial poly(A) polymerase PAPD1 is a potential candidate gene for the extreme obesity related phenotypes in mammals.

People with obesity, especially extreme obesity, are at risk for many health problems. However, the responsible genes remain unknown in >95% of severe obesity cases. Our previous genome-wide scan of Wagyu x Limousin F2 cattle crosses with extreme phenotypes revealed a molecular marker significantly associated with intramuscular fat deposition. Characterization of this marker showed that it is orthologous to the human gene KIAA1462 located on HSA10p11.23, where a major quantitative trait locus for morbid obesity has been reported. The newly identified mitochondrial poly(A) polymerase associated domain containing 1 (PAPD1) gene, which is located near this marker, is particularly interesting because the polymerase is required for the polyadenylation and stabilization of mammalian mitochondrial mRNAs. In the present study, both cDNA and genomic DNA sequences were annotated for the bovine PAPD1 gene and ten genetic markers were detected in the promoter and exon 1 region. Among seven markers assayed on approximately 250 Wagyu x Limousin F2 animals, two single nucleotide polymorphisms (SNPs) in the promoter region were significantly associated with intramuscular fat (P<0.05). However, there was a significant interaction (P<0.05) between a third SNP, which causes an amino acid change in coding exon 1, and each of these two promoter SNPs on intramuscular fat deposition. In particular, the differences between double heterozygous animals at two polymorphic sites and the slim genotype animals exceeded 2.3 standard deviations for the trait in both cases. Our study provides evidence for a new mechanism--the involvement of compound heterosis in extreme obesity, which warrants further examination.

Adipose Tissue↗
PubMedDate not supplied

The case of the high-risk safety product.

After several days of meetings, J.F. Winchester, president of MDC Industries, felt no closer to a decision. MDC, a manufacturer of wall and ceiling panels, was considering whether to exercise an option to buy a new and safer wallboard technology. The product was being touted as revolutionary, but, Winchester wondered, could MDC afford to carry the flag? According to its inventor, Robert Goerner, Smoke-Safe would be a vast improvement over standard safety-rated wallboard. With almost the same flame-retardant properties, Smoke-Safe had the advantage of giving off almost no fumes or smoke in fire tests. And, Winchester knew, most fire-related deaths are from smoke, not flames. Indeed, the numbers were grimly persuasive: 82% of fire-related injuries involving standard panels were caused by smoke inhalation. What's more, Smoke-Safe would cost about the same to manufacture as MDC's current wallboard. But MDC had several other good options for spending the $5 million Goerner was asking; building plastics was only one of its profit centers. And the prospect of launching a campaign to change building codes in order to market Smoke-Safe, which could spark a fight with competitors, was daunting. Since its current wallboard gave MDC only 18% of the wallboard market, many industry insiders speculated whether MDC had the market clout to influence major cities to revise their codes. Six experts in marketing, law, and ethics advise MDC Industries on how it can balance ethical and business imperatives in making its decision.

Consumer Product Safety↗
PubMed1993

12 steps to EDI's (electronic data interchange) full advantages.

Only 50 hospitals in the United States are fully EDI-capable; the rest miss out on many benefits. Here's how to claim some of those benefits for your own health care facility. Plus, how bar codes have changed one hospital's way of doing business.

Computer Communication Networks↗
PubMed1980

Veterans Administration--Veterans education; eligibility for vocational rehabilitation and educational assistance--character of discharge. Final regulations.

The Veterans Administration is amending its regulations concerning eligibility for vocational rehabilitation and educational assistance under chapters 31 and 34, title 38, United States Code. These changes are necessary in order to implement a law enacted October 8, 1977. Most of the changes are of a minor technical nature. The regulatory amendments will implement the provisions of the law.

Eligibility Determination↗
PubMed1984

Part 2, Responding to PPS. Development and interpretation of the diagnosis-related groups (DRGs).

As they are now, defined, the DRGs form a manageable, clinically coherent set of patient classes that relate a hospital's case mix to the resource demands and associated costs experienced by the hospital. DRGs are defined based on the principal diagnosis, secondary diagnoses, surgical procedures, age and discharge status of the patients treated. Through DRGs, hospitals can gain an understanding of the patients being treated, the costs incurred and within reasonable limits, the services expected to be required. The classification of patients into DRGs is a constantly evolving process. As coding schemes change, as more comprehensive data is collected or as medical technology or practice changes, the DRG definitions will need to be reviewed and revised.

Costs and Cost Analysis↗
PubMed1984

Selected bibliography and glossary on DRG's prospective pricing.

In 1982, the Tax Equity and Fiscal Responsibility Act modified the Section 223 Medicare Hospital reimbursement limits to include a case mix adjustment based on DRG's. In 1983, Congress amended the Social Security Act to include a national DRG-based hospital prospective payment system for all Medicare patients. In the view of many physicians and administrators the current formulation of DRG's constitute a workable and clinically coherent set of classifications that relate a hospital's case mix to the resources used and costs incurred by the hospital. DRG's are delineated based on principal diagnosis, secondary diagnosis, surgical procedures, age and the discharge status of the patients treated. Through DRG's, hospitals are able to gain an understanding of the patients they treat, the costs incurred and within reason, can anticipate the services required for specific illness. The classification of DRG's is a constantly evolving process. As coding procedures change, as more comprehensive data is collected, and as medical technology and treatment practices change, DRG's will need to be re-examined and revised. The following bibliography and glossary of terms highlights several key words and phases which are relevant to the overall discussion of DRG's.

Bibliographies as Topic↗
PubMed1999

Employment-based health insurance: a look at tax issues and public opinion.

This Issue Brief provides background information on the employment-based health insurance system and its alternatives. The report discusses the advantages and disadvantages of the current employment-based health insurance system, the current tax treatment of health insurance, and the strength and weaknesses of recent proposals to introduce tax credits. It presents findings from the public opinion survey conducted by the Employee Benefit Research Institute on public attitudes toward health insurance and summarizes recent research on the effects of tax changes on employment-based health benefits and the uninsured. Employment-based health plans are the most common source of health insurance among nonelderly individuals in the United States, providing coverage to nearly two-thirds of this population in 1997. Health insurance is probably the benefit most used and valued by workers and their families. Sixty-four percent of respondents to a recent survey rated employment-based health insurance benefits as the most important benefit. Despite essentially five years of very low health care cost increases and the recent increase in the percentage of Americans with employment-based health insurance coverage, the uninsured population has continued to rise. This has resulted in a new interest among policymakers in finding ways to reverse this trend. One question that continues to be asked is whether the employment-based health insurance system is the appropriate mechanism for expanding health insurance to the uninsured. Employment-based health plans are popular because they offer many advantages over other forms of health insurance and types of delivery systems. However, there are also potential drawbacks to the employment-based system. The advantages include reduced risk of adverse selection, group-purchasing efficiencies, employers acting as a workers' advocate, delivery innovation, and health care quality. The disadvantages include an unfair tax treatment, lack of portability and job lock, little choice of health plans, and lack of universal coverage. The tax credit proposals for health insurance, which come in all shapes and sizes, would either enhance the current employment-based health insurance system or put it at risk. This has potentially enormous public policy implications, since the vast majority of Americans get their health insurance coverage through employers. Such a change may also have political implications, as public opinion currently may not support such a fundamental change in the U.S. health insurance system. A recent public opinion survey conducted by the Employee Benefit Research Institute found that 68 percent of Americans with employment-based health insurance were satisfied with the current mix of benefits and wages. The EBRI survey found that under a changing tax code scenario, there is still strong support for the employment-based system. Strong support for the employment-based system may be the result of respondents' lack of confidence in their ability to choose the best health plan if their employer stopped offering health insurance.

Data Collection↗
PubMed1999

The National Population Health Survey--its longitudinal nature.

OBJECTIVES: This article discusses some of the benefits and challenges of data from a longitudinal panel as exemplified by the National Population Health Survey (NPHS). DATA SOURCE: The NPHS collects both cross-sectional and longitudinal data from a sample of randomly selected individuals. The longitudinal sample will be reinterviewed every 2 years for up to 20 years. Two NPHS cycles have been completed: cycle 1 in 1994/95 and cycle 2 in 1996/97. SUMMARY: Selected findings from the NPHS are presented to illustrate the benefits of longitudinal data. An overview of questionnaire content, collection methods follows, and sample design is provided. A summary of response rates is followed by a discussion of the methods used to maintain response and to adjust the survey weights in order to reduce nonresponse bias. Confidentiality, dissemination, inconsistencies in reporting, proxy reporting and changes in coding conventions are also discussed.

Canada↗
PubMed2000

An evaluation of statewide strategies to reduce antibiotic overuse.

BACKGROUND: The rapid increase of antibiotic resistance poses a significant threat to human health. Overuse of antibiotics has been linked to rates of antibiotic resistance. This study assessed the utility of two common interventions--1) practice profiling and feedback and 2) patient education materials--implemented to decrease antibiotic prescribing for pediatric upper respiratory infections (URIs). METHODS: Based on Medicaid regions in Kentucky, primary care physicians managing pediatric respiratory infections in Medicaid were randomized into four groups. Groups received either 1) performance feedback only, 2) patient education materials only, 3) both feedback and education materials, or 4) no intervention. Participating physicians had their antibiotic prescribing assessed for the period of July 1, 1996, to November 30, 1997, with an intervention in June 1997. The study included 216 physicians and 124,092 episodes of care. RESULTS: All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods. Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group. Physicians did not change their coding of illness to justify antibiotics after the intervention, and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs. CONCLUSIONS: These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing. Antibiotic prescribing for viral respiratory infections continues to increase, suggesting concomitant increases in antibiotic resistance.

Adult↗
PubMed1999

Genetic alterations in the transforming growth factor receptor complex in sporadic endometrial carcinoma.

Cellular responses to the transforming growth factor beta (TGFbeta) ligand, including inhibition of cell proliferation, are mediated by a heteromeric receptor complex composed of TGFbeta types I and II receptors (TbetaR-I and TbetaR-II). Loss of responsiveness to TGFbeta, attributed to inactivation of the TbetaR complex, has been implicated in the development of tumors in a number of human epithelial and lymphoid tissues. To gain a better understanding of TGFbeta signal transduction pathways in endometrial carcinogenesis, we have investigated the role of the TbetaR complex by evaluating the TbetaR-I and TbetaR-II genes for mutations throughout the entire coding region in human sporadic endometrial tumors. Using reverse transcription-PCR, "Cold" single-strand conformation polymorphism analysis, and direct DNA sequencing, it was found that 1 of 39 (2.6%) and 7 of 42 samples (17%) contained code-altering changes in the kinase domain of TbetaR-I and TbetaR-II, respectively. In 7betaR-I, a 3-bp deletion was found resulting in replacement of Arg and Glu at codon 237 and 238 by Lys. With TbetaR-II, mutations were found in the kinase, the extracellular, and the C-terminal domains. No frameshift mutations were detected; however, a silent population polymorphism (AAC-->AAT at codon 389) in TbetaR-II was found in 19 of 42 (44%) tumor samples. These results suggest that alteration in TbetaR-II, but not TbetaR-I, has an important role in the development of endometrial carcinoma.

Activin Receptors, Type I↗
PubMed2002

A team approach in palliative care: enhancing outcomes.

While most Americans envision a "good death" as one occurring quickly and painlessly at home surrounded by loved ones, many people do not die in this fashion. Palliative care focuses on holistic treatment of patients whose disease is not responsive to curative treatment, and strives to improve quality of life for patients and families at end-of-life (EOL). This hospital-based study examines the extent to which a palliative care consultant team makes a difference in EOL for patients and families. Data were collected from a convenience sample of 50 hospitalized patients referred to an interdisciplinary palliative care consulting team at a South Dakota tertiary hospital during 2001. Various palliative care interventions were introduced during the course of hospitalization, and data were collected two days later to see if quality of life had improved. Statistically significant improvements were found in pain levels, non-pain symptom management, numerous psychosocial measures of quality of life, change in code status, and perceptions of communication and treatment during hospitalization. The study demonstrates that consultations with a palliative care team are beneficial and enhance the EOL experience for patients and families.

Adult↗
PubMed2002

[Study on the Relationship between susceptibility of stomach neoplasm cancer and polymorphism of inducible nitric oxide synthase gene].

OBJECTIVE: To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people. METHODS: A community-based case-control study was designed. Ninety-three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty-six controls served as controls. RESULTS: C-->T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509 I restriction enzyme (we called it C-->T polymorphism). The T allele gene frequency in the control group was 13.21%. No statistically significant difference was found between C-->T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C-->T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C-->T polymorphism occurred. CONCLUSION: C-->T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco-related but CagA negative types of intestinal stomach cancer and stomach cardia cancer.

Antibodies, Bacterial↗
PubMed1992

High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors.

We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events.

Base Sequence↗
PubMed1992

p53 mutations in spontaneously immortalized 3T12 but not 3T3 mouse embryo cells.

We have asked whether p53 mutations are involved in the process of spontaneous immortalization of mouse embryo cells. Cells from Swiss mouse embryos were used to prepare 3T3 and 3T12 lines according to the protocol of Todaro & Green [(1963). J. Cell Biol., 17, 299-313]. After the cells emerged from crisis, p53 sequences were amplified by polymerase chain reaction (PCR) from both RNA and DNA. The sequence of the aggregated cDNA from each of six 3T3 lines showed no evidence of mutation. PCR-amplified p53 cDNA from two 3T3 lines was cloned, and individual clones in M13mp19 were partially sequenced. One cell ine showed a single, non-coding nucleotide change in 2/8 independent clones. Nine cDNA clones from the second 3T3 lines were sequenced, and no single nucleotide changes appeared more than once. The mutations which appeared only once were not detected in clones of genomic DNA. Since these apparent mutations are probably reverse transcriptase or Taq polymerase errors, we conclude that both the 3T3 lines contained only wild-type p53. In two out of three independent 3T12 lines however, missense mutations were readily observed in the aggregate cDNA sequence. Restriction fragment length polymorphism and Southern blot analyses of the genomic DNA indicated that these cells were homozygous for the mutations. The p53 protein molecules in four cell lines were analysed by immunoprecipitation: one 3T12 line showed the pattern of antibody reactivity characteristic of some p53 mutants, while the others displayed the wild-type pattern. We conclude that p53 mutations arise and are strongly selected for during immortalization according to the 3T12 but not the 3T3 protocol.

Amino Acid Sequence↗