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PubMed2002

Does more "appropriateness" explain higher rates of cardiac procedures among patients hospitalized with coronary heart disease?

BACKGROUND: There have been few studies of the extent to which differences in the pool of patients being managed might account for geographic variations in treatment rates. OBJECTIVE: For two cardiac procedures, cardiac catheterization and revascularization, we evaluate the hypothesis that differences in "the percentage of patients for whom the procedure is appropriate" is a factor explaining variations in use rates among those hospitalized with coronary heart disease (CHD). RESEARCH DESIGN: Based on hospital utilization patterns in Massachusetts in 1990, we created 70 small geographic areas. Using 1992 Massachusetts Peer Review Organization data, areas were ranked from highest to lowest based on (empirical-Bayes-adjusted) hospitalization rates for each procedure. One thousand seven hundred four cases from 43 hospitals were sampled, roughly half each from high and low use areas. Half had a procedure and half were candidates for the same procedure but did not have it. For each procedure, medical records were reviewed to determine whether the procedure was (or, for those not having it, would have been) appropriate, based on criteria developed using a modified Delphi approach. RESULTS: Among those having either procedure, appropriateness rates were similar in high and low rate areas (P = 0.59 for catheterization and P = 0.30 for revascularization). However, among candidates for either procedure who did not have it, appropriateness for performing the procedure was greater in high-rate areas (41.4% vs. 32.1%, P = 0.05 for catheterization; 71.2% vs. 57.2%, P = 0.003, for revascularization). CONCLUSION: Among those hospitalized with CHD, appropriateness rates for two cardiac procedures are higher in areas with higher use rates.

Aged↗

PubMedDate not supplied

Explaining Mexican American workers' hearing protection use with the health promotion model.

BACKGROUND: Mexican American workers are vulnerable to noise-induced hearing loss, the most common occupational disease in the United States. OBJECTIVES: The purpose was to test the applicability of the Health Promotion Model to Mexican American workers' use of hearing protection devices. METHOD: A correlational descriptive design and path analysis were used to determine the relationships between cognitive-perceptual factors, modifying factors and use of hearing protection devices. A questionnaire was completed by a total of 119 workers in three garment manufacturing plants. Interviews were conducted with the occupational health nurse or safety director in each plant to determine the policy regarding hearing protection also. RESULTS: Factors that directly influenced the use of hearing protection devices were a clinical definition of health, benefits of and barriers to use of hearing protection devices, self-efficacy in the use of hearing protection devices and perceived health status (R2 =.25, p <.01). An exploratory analysis allowing a direct relationship of modifying factors with the dependent variable explained additional variance in use of hearing protection devices through the contribution of situational factors (R2 =.55, p <.01). CONCLUSIONS: Important factors related to Mexican American workers' use of hearing protection devices were identified to provide direction for nursing interventions. Future research should further test the explanatory capabilities of the Health Promotion Model, explore the importance of situational influences on health behavior, and ensure reliable measures of all model components for this population.

Adult↗

PubMed2001

Does education explain ethnic differences in myopia prevalence? A population-based study of young adult males in Singapore.

PURPOSE: To study interethnic variation in myopia prevalence and severity in young adult males in Singapore and to determine whether these variations are related to differences in education level. METHODS: A population-based survey of refractive errors in a cohort of 15,095 military conscripts between July 1996 and June 1997 using noncycloplegic autorefraction and a standard questionnaire. Prevalence rates of myopia (<-0.5 D) and severe myopia (<-6.0 D) were determined for Chinese, Malay, and Indian men; prevalence rate ratios were compared after adjusting for education level. RESULTS: Singapore has one of the highest prevalences of myopia (79.3%) and severe myopia (13.1%), with Chinese having higher rates (82.2%, 95% confidence interval 81.5, 82.9) compared with Indians (68.7%, 95% confidence interval 65.1, 67.1) and Malays (65.0%, 95% confidence interval 62.9, 67.1). Education was strongly associated with prevalence and severity of myopia. However, significant interethnic variation persisted after adjusting for education. CONCLUSIONS: There is a high prevalence of myopia in Singapore. Although prevalence and severity of myopia were strongly associated with education, interethnic variation observed was not fully explained by differences in education level.

Adolescent↗

PubMed1988

Choreoathetosis induced by ordinary phenytoin levels, explained by high free fraction?--A case report.

Choreoathetosis was induced by phenytoin therapy in an 81-year-old epileptic woman. The plasma concentration of phenytoin was 59 to 80 mumol/L when side effects appeared. Choreoathetosis at ordinary plasma levels has previously been attributed to a preexisting brain damage. In this case, however, it may be explained by a high free fraction (19%) of the phenytoin plasma concentration.

Aged↗

PubMed2003

Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations.

The relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatment-naive patients who began taking nelfinavir, 1,250 mg BID + two nucleoside reverse transcription inhibitors (NRTIs). Nelfinavir concentration ratios were calculated by dividing each individual nelfinavir level by the time-adjusted population value. Virologic failure was defined as either no response (a detectable viral load after 6 months) or a relapse (detectable viral load after being undetectable, or an increase in viral load >1 log above nadir). Forty-eight patients were included with a median follow-up period of 8 months. The median concentration ratio of nelfinavir was 0.98 (interquartile range, 0.76-1.47). Virologic failure was observed in 29% of the patients. In a univariate analysis, the nelfinavir concentration ratio appeared to be the single determinant that was related to virologic failure (P = 0.039). Patients with a median ratio <0.90 had a relative risk of 3.0 (95% CI, 1.2-7.6) for virologic failure. Using this threshold, virologic failures were detected with 64% sensitivity and 74% specificity (P = 0.014). Virologic failure of nelfinavir-containing triple therapy can be explained, to a large extent, by low plasma levels of nelfinavir.

Adult↗

PubMed1987

Evidence that the difference in kidney graft survival in DRw6+ and DRw6- recipients may be explained by a blood transfusion policy that is disadvantageous for DRw6+ recipients.

Kidneys transplanted to HLA-DRw6+ recipients have been shown to have an inferior graft survival compared with DRw6- patients. Because pretransplant blood transfusions influence kidney graft survival, we investigated whether the number of blood transfusions contributes to the observed poor graft survival in DRw6+ patients. We have found that the difference in graft survival in DRw6+ and DRw6- recipients may be explained by a blood transfusion policy that is disadvantageous for DRw6+ recipients. Thus, graft survival in DRw6+ recipients was excellent for those who had received only a single transfusion. More transfusions resulted in a gradual decrease in graft survival. When the number of transfusions exceeded 5, graft survival improved again. By contrast, DRw6- recipients showed an improvement in graft survival with an increasing number of transfusions. DRw6+ recipients therefore display inferior graft survival only when they receive 3-5 transfusions. This finding provides a possible explanation as to why the "DRw6 effect" is a controversial issue, and it suggests that DRw6+ recipients should be given a different pre-transplant transfusion protocol than DRw6- patients.

Cyclosporins↗

PubMed1995

CDKN2 explains part of the clinical phenotype in Dutch familial atypical multiple-mole melanoma (FAMMM) syndrome families.

Combined multi-point linkage analysis in seven Dutch families with FAMMM syndrome confirmed the location of a melanoma susceptibility (MLM) gene in the 9p21 area. The occurrence of a shared high-risk haplotype in six of the families strongly suggests a founder effect in the Leiden region. No indication for locus heterogeneity was observed. Recently, the CDKN2 (p16) gene, an important regulator of the cell cycle, was isolated from the 9p21 region. A 19-bp germline deletion in the CDKN2 gene was detected in the high-risk haplotype, suggesting CDKN2 to be identical to MLM. Loss of heterozygosity studies in melanoma and pancreatic carcinoma from gene carriers strongly support the view that CDKN2 is a general tumour suppressor gene predisposing not only to melanoma but also to other malignancies. Interestingly, the occurrence of apparent clinical FAMMM cases with melanoma but without the high-risk deletion haplotype suggests the necessity of additional (naevus) genes to explain the complete FAMMM phenotype.

Adolescent↗

PubMed2006

Do changes in lymph node status distribution explain trends in survival of breast cancer patients in Denmark?

We studied the impact on survival of changes in breast cancer patients' distribution by lymph node status at the time of diagnosis. Our study included breast cancer patients diagnosed from 1978 to 1994 in Denmark, where the treatment schemes for breast cancer patients were fairly stable, and where mammography screening was limited. We measured lymph node status by the proportion of positive lymph nodes of all excised lymph nodes, as assessed by a pathologist. This measure was available for two-thirds of the breast cancer patients. The outcome was 5-year relative survival. Changes in lymph node status distribution explained half of the improvement in 5-year relative survival, and seem to be the single most important cause behind the improved survival of breast cancer patients in Denmark.

Aged↗

PubMed2000

Known variant DPYD alleles do not explain DPD deficiency in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) degrades over 80% of administered 5-fluorouracil (5FU), thereby regulating the efficacy of this commonly used anticancer agent. DPD activity is highly variable (8-21-fold) and individuals with reduced activity have a high risk of 5FU toxicity. DPYD encodes DPD protein and 13 different mutations have been reported in DPD-deficient subjects. However, the contribution of these variant genotypes to polymorphic DPD activity in vivo is not clear. The previously described DPYD mutations are contained in 10 exons. These 10 exons were sequenced in a cohort of cancer patients with reduced (n = 23) or normal (n = 14) DPD activity to determine the contribution of each variant allele to low DPD activity in vivo. Eight of the 13 previously defined DPYD mutations (G62A, delta TCAT295-298, C703T, G1003T, G1156T, delta C1897, G2657A, and G2983T) were not detected. A previously defined exon 13 mutation (G1601A) was detected in three individuals with reduced DPD activity. An exon 14 splice donor site mutation (intron14 G1A) was detected in a normal DPD activity individual. It was demonstrated that T85C, A1627G and G2194A are common polymorphisms. A novel exonic mutation (T1679G) was detected in a patient with reduced DPD activity and 5FU toxicity. In addition, three novel common polymorphisms were detected in introns 10 and 13. Only three patients did not have any mutations and 30 had multiple DPYD mutations in the regions examined. However, only 17% (4/23) of the patients with a low DPD phenotype have a molecular basis for reduced activity. Although novel DPYD variants have been identified in this study, the 17 DPYD mutations now described do not entirely explain polymorphic DPD activity and toxic response to 5FU. These data emphasize the complex nature of the molecular mechanisms controlling polymorphic DPD activity in vivo.

Alleles↗

PubMed1996

The fall of cardiac output in endotoxemic rats cannot explain all changes in organ blood flow: a comparison between endotoxin and low venous return shock.

During endotoxin shock mean arterial pressure (MAP) and cardiac output (CO) fall, and the latter is redistributed. To evaluate whether these changes are solely caused by the low output, or are also based on endotoxin itself, we compared regional hemodynamic changes during endotoxemia with those in a nonendotoxemic state of decreased CO in anesthetized rats. In group E (n = 10) endotoxin Escherichia coli O127:B8 (8 mg.kg-1) was infused from t = 0 till t = 60 min. In group B (n = 10) the same decrease of CO and MAP was obtained as in group E by inflating a balloon in the inferior caval vein, distal to the renal veins, from t = 0 till t = 60 min. We measured MAP, CO (thermodilution), central venous pressure, heart rate, organ blood flow, and redistribution of CO (microspheres), arterial lactate and glucose, and hematocrit. MAP and CO decreased (p < .05) in both groups (by 30 and 50%, respectively at t = 60). Heart rate, hematocrit, arterial lactate, and arterial glucose were significantly higher (p < .05) in group E (by 17, 12, 180, and 55%, respectively). Blood flow to most organs had similarly decreased in both groups. The decreased intestinal blood flow lead to macroscopic damage only in group E. Blood flows (absolute or as percentage of CO) to heart, hepatic artery, and diaphragm, however, had significantly increased in group E while blood flows to skin, skeletal muscle, and stomach had decreased more in group E. Except for the heart these differences could be explained by increased work load (detoxification: liver; hyperventilation: diaphragm, muscle) and thus to a more pronounced redistribution at the expense of skin and muscle blood flow. Regional hemodynamic changes during endotoxemia thus could largely be attributed to decrease of CO and redistribution of the circulating blood volume. In the heart, endotoxin seemed to exert effects independent of the hypodynamic state. This was also true for the intestinal damage and the rise in hematocrit and arterial lactate.

Animals↗

PubMedDate not supplied

A Mathematical simulation to explain the coordinated functions of efflux and metabolism limiting the transport of anti-HIV agents across Caco-2 cells.

OBJECTIVES: The purpose of this study was to simulate a mathematical model that explains the coordinated function of P-glycoprotein (P-gp) and/or CYP3A4 in human intestinal enterocytes. In addition, this study aimed to determine the efflux interactions of anti-HIV protease inhibitors. METHODS: Human colon carcinoma-derived Caco-2 cells were selected as a model system to evaluate the effects of P-gp-mediated efflux of HIV protease inhibitors. Anti-HIV agents ritonavir and saquinavir were selected as model drugs to determine efflux interactions. An absorption-metabolism classification system is hence proposed based on substrate specificities of drugs toward P-gp and/or CYP3A4 and their probable interactions with other compounds. RESULTS: Enhanced apical to basal (A-B) ritonavir transport was observed on coadministration of saquinavir. Saturable, concentration-dependent inhibition of ritonavir efflux from Caco-2 monolayers was also observed with saquinavir. The IC(50) values of ritonavir (as a self-inhibitor) and saquinavir from dose-response curves, estimated by fitting the data to nonlinear equations, were found to be 7.15 and 33.2 micromol/L, respectively. The respective K(i) values determined were 8.5 and 28.91 micromol/L. The experimentally obtained K(i) values decreased in the close approximation with the IC(50) values. CONCLUSION: Proposed mathematical simulations may prove to be a useful tool in predicting drug interactions by inhibition of P-gp mediated efflux and CYP3A4-mediated metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Can health care utilization explain the association between socioeconomic status and back pain?

STUDY DESIGN: Cross-sectional population-based study. OBJECTIVES: To assess whether the association between socioeconomic status and severe back pain can be explained by the preceding health care utilization for back pain. SUMMARY OF BACKGROUND DATA: The ways in which socioeconomic status affects the occurrence of back pain are unclear. METHODS: Age- and gender-adjusted odds ratios with 95% confidence intervals for the association between indicators of socioeconomic status and severe current back pain (high intensity and/or high disability: no/yes) were investigated in an interview among 770 study participants out of 1113 study participants with a recent history of back pain in a survey among 2731 adults. RESULTS: The point prevalence of severe current back pain (39.8%) was related to educational level and health insurance status. Prior health care utilization for back pain was about 2-fold more prevalent in adults with severe current back pain. Members of private health insurance (odds ratio 0.60, 95% confidence interval 0.37-0.99) were less likely to report prior consultation of a general practitioner for back pain. Members of sick funds for white-collar workers (odds ratio 2.81, 95% confidence interval 1.43-5.51) and private insurance (odds ratio 2.81, 95% confidence interval 1.02-6.24) and individuals with intermediate educational level (odds ratio 1.76, 95% confidence interval 1.05-2.95) utilized more physical therapy for the treatment of back pain. After additionally adjusting for health care utilization, the associations between educational level or health insurance status and severe current back pain remained unchanged. CONCLUSIONS: The data suggest that education, health insurance status, and health care utilization are independently associated with severe current back pain in a society with universal access to health care.

Adult↗

PubMed2006

A theory and model to explain the skin melanoma epidemic.

Before 1955, the incidence of malignant melanoma in Nordic countries increased from birth to approximately 30 years of age, when it levelled off to around five cases per 100,000 person-years. From 1957 onwards, the incidence no longer stabilized at the age of 30 years, but continued to increase with age to at least 100 cases per 100,000 person-years. The aims of this study were to examine this sudden change in melanoma trends and to develop an explanatory model. The Nordic Cancer Registries and the American Cancer Society provided age-specific incidence data. Birth cohorts of melanoma incidence for men were plotted against calendar year and age. A theory and a corresponding mathematical model were developed to explain the time trends in all cohorts, as well as the reported age-specific incidence and age-standardized incidence over time. A statistical distribution of time to sickness fitted all the post-1957 data. Earlier studies have indicated that body-resonant frequency modulation broadcasting radiation from 1955 onwards may affect melanoma incidence. The proposed model may shed light on the melanoma epidemic and may be useful in predicting future melanoma trends based on known birth cohort data and possible effects from policy changes with regard to population exposure to electromagnetic radiation.

Adult↗

PubMed2003

Hyperprolactinemia in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: pilot study.

Recently, an increased risk of venous thromboembolism in patients on antipsychotic drugs has been reported, but the molecular etiology is still unknown. Most antipsychotic drugs act as dopamine antagonists, and some of them cause hyperprolactinemia. Hyperprolactinemia has recently been found to cause increased platelet activation via potentiating ADP effects on human platelets. We assessed prolactin values as well as ADP-stimulated and thrombin receptor activator 6-stimulated expression of the platelet activation marker P-selectin in 20 consecutive patients under therapy with antipsychotic drugs. We detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in patients on antipsychotic drugs, revealing a significant higher platelet stimulation in hyperprolactinemic patients on antipsychotic drugs than in normoprolactinemic controls. Therefore, hyperprolactinemia might be the yet unknown acquired risk factor in patients on antipsychotic drugs explaining the increased risk for venous thromboembolism in these patients.

Adolescent↗

PubMed2003

Energetic characteristics of the new transthyretin variant A25T may explain its atypical central nervous system pathology.

Transthyretin (TTR) is a tetrameric protein that must misfold to form amyloid fibrils. Misfolding includes rate-limiting tetramer dissociation, followed by fast tertiary structural changes that enable aggregation. Amyloidogenesis of wild-type (WT) TTR causes a late-onset cardiac disease called senile systemic amyloidosis. The aggregation of one of > 80 TTR variants leads to familial amyloidosis encompassing a collection of disorders characterized by peripheral neuropathy and/or cardiomyopathy. Prominent central nervous system (CNS) impairment is rare in TTR amyloidosis. Herein, we identify a new A25T TTR variant in a Japanese patient who presented with CNS amyloidosis at age 42 and peripheral neuropathy at age 44. The A25T variant is the most destabilized and fastest dissociating TTR tetramer published to date, yet, surprising, disease onset is in the fifth decade. Quantification of A25T TTR in the serum of this heterozygote reveals low levels relative to WT, suggesting that protein concentration influences disease phenotype. Another recently characterized TTR CNS variant (D18G TTR) exhibits strictly analogous characteristics, suggesting that instability coupled with low serum concentrations is the signature of CNS pathology and protects against early-onset systemic amyloidosis. The low A25T serum concentration may be explained either by impaired secretion from the liver or by increased clearance, both scenarios consistent with A25T's low kinetic and thermodynamic stability. Liver transplantation is the only known treatment for familial amyloid polyneuropathy. This is a form of gene therapy that removes the variant protein from serum preventing systemic amyloidosis. Unfortunately, the choroid plexus would have to be resected to remove A25T from the CSF-the source of the CNS TTR amyloid. Herein we demonstrate that small-molecule tetramer stabilizers represent an attractive therapeutic strategy to inhibit A25T misfolding and CNS amyloidosis. Specifically, 2-[(3,5-dichlorophenyl)amino]benzoic acid is an excellent inhibitor of A25T TTR amyloidosis in vitro.

Amyloid Neuropathies, Familial↗

PubMed2006

Variables explaining functional recovery following motor stroke.

Few well-designed descriptive studies focus exclusively on patients after motor stroke. This study describes a cohort of participants after motor stroke and assesses the extent to which five key variables explain the variation in functional recovery 3 months after stroke. Prospective data were collected (N=100) on age, lesion volume, motor strength, cognition, and poststroke function during the acute care hospital admission. Instruments included magnetic resonance imaging (MRI) to provide a measure of lesion volume, the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (NCSE) to measure cognitive status, and the National Institutes of Health Stroke Scale (NIHSS) to measure motor strength. The Functional Independence Measure (FIM) was used to measure baseline function and functional recovery 3 months after stroke. Descriptive and hierarchical multiple regression analyses were used to describe the cohort and predict functional recovery. The means for key variables during acute care were 65 (+/-15) years of age, lesion volume 21.5 (+/-44.7) cm3, NIHSS 6.34 (+/-3.55), MMSE 24.38 (+/-4.82), NCSE 64.33 (+/-13), and FIMTM 94.05 (+/-19.31). Age, cognitive status, and initial function accounted for 42% of the variance in functional recovery 3 months after stroke. Results indicate that neuroscience nurses need to add cognition to their focus during the fast-paced acute phase of care following motor stroke.

Aged↗

PubMed2005

Eucalyptus foliar chemistry explains selective feeding by koalas.

The koala is the quintessential specialist herbivore, feeding almost exclusively on Eucalyptus foliage. Consequently, the limitations imposed on the koala's diet by plant defences indicate the extent to which evolutionary adaptations allow mammalian herbivores to circumvent such defences. We tested whether a recently discovered group of plant secondary metabolites, the formylated phloroglucinol compounds (FPCs), deters koalas from feeding on some eucalypt foliage. We found that captive koalas ate less foliage in a single night from trees with high FPC concentrations. Individual trees also differ in the types of FPC they possess, but for a given eucalypt species, most FPCs were similarly effective deterrents. Two closely related and sympatric eucalypt species could be clearly separated by the amounts that koalas ate from each; however, this difference could not be explained by total FPC concentrations alone. We suggest, that in this case, the presence of a distinct type of FPC deters koala herbivory on the less palatable species, and may have facilitated the evolutionary divergence of these species. We conclude that plant defences probably play an important role in determining the distribution and abundance of koalas.

Animals↗

PubMed2025

Blood capillary geometry helps to explain the link between genome size and metabolic rates.

In the past decades, several authors have investigated the possibility that genome size is correlated with metabolic rates, obtaining conflicting results. The main biological explanation among the supporters of this correlation was related to the nucleotypic effect of the genome size, which, determining the cellular volume and hence the surface area-to-volume ratio, influences cellular metabolism. In the present study, I tested a different hypothesis: genome size, influencing red blood cell (RBC) volume, is correlated with capillary density and diameter. These, in turn, are (directly and inversely) correlated with mass-specific metabolic rates, and this can explain the link between genome size and metabolic rates. I have found that these correlations are significant in vertebrates with nucleated RBCs (non-mammals), but not in species with enucleated RBCs (i.e. mammals). Although further research is needed (in particular to understand how to test the correlation between genome size and metabolic rates in ectotherms), my results show that genome size and metabolic rates act on each other through a physical constraint. Through enucleation, mammals (but also some fish and salamanders) removed this constraint.

Animals↗