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Biomedical subjects

M Miller

Publications and source records attributed to M Miller.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effectiveness of high doses of simvastatin as monotherapy in mixed hyperlipidemia.

Twenty subjects with mixed hyperlipidemia participated in a 3-arm crossover trial to evaluate the effectiveness of high-dose simvastatin as monotherapy. Significant reductions were observed in atherogenic lipids and lipoproteins. The highest dose of simvastatin also resulted in significant increases in high-density lipoprotein cholesterol (21%) with a comparable increase in large, protective high-density lipoprotein particles.

Drug Administration Schedule↗
PubMed2001

The response of a selfish herd to an attack from outside the group perimeter.

According to the selfish herd hypothesis, animals can decrease predation risk by moving toward one another if the predator can appear anywhere and will attack the nearest target. Previous studies have shown that aggregations can form using simple movement rules designed to decrease each animal's Domain of Danger. However, if the predator attacks from outside the group's perimeter, these simple movement rules might not lead to aggregation. To test whether simple selfish movement rules would decrease predation risk for those situations when the predator attacks from outside the flock perimeter, we constructed a computer model that allowed flocks of 75 simulated fiddler crabs to react to one another, and to a predator attacking from 7 m away. We attacked simulated crab flocks with predators of different sizes and attack speeds, and computed relative predation risk after 120 time steps. Final trajectories showed flight toward the center of the flock, but curving away from the predator. Path curvature depended on the predator's size and approach speed. The average crab experienced a greater decrease in predation risk when the predator was small or slow moving. Regardless of the predator's size and speed, however, predation risk always decreased as long as crabs took their flock-mates into account. We conclude that, even when flight away from an external predator occurs, the selfish avoidance of danger can lead to aggregation.

Animals↗
PubMed2001

Firearm availability and unintentional firearm deaths.

BACKGROUND: Between 1979 and 1997, almost 30,000 Americans died from unintentional firearm injuries, half of whom were under 25 years of age and 4,600 of whom were less than 15 years old. PURPOSE: To explore the association between state firearm levels and rates of unintentional firearm deaths by age group, accounting for several potential confounders. METHODS: The study used a proxy for firearm availability and pooled cross-sectional time-series data on unintentional firearm deaths for the 50 United States from 1979 to 1997. Negative binomial models were used to estimate the association between firearm availability and unintentional firearm deaths. RESULTS: A statistically significant and robust association exists between gun availability and unintentional firearm deaths for the US as a whole and within each age group. Multivariate analysis found that, compared to states with the lowest gun levels, states with the highest gun levels had, on average, 9 times the rate of unintentional firearm deaths. These results hold among men and women, for Whites and African Americans. CONCLUSION: Of the almost 30,000 people who died in unintentional firearm deaths over the 19-year study period, a disproportionately high number died in states where guns are more prevalent. The results suggest that the increased risk of unintentional violent death among all age groups is not entirely explained by a state's level of poverty, urbanization, or regional location.

Adolescent↗
PubMed2001

Helicobacter pylori heat shock protein 60 and risk of coronary heart disease: a case control study with focus on markers of systemic inflammation and lipids.

AIM: it has been suggested that antibodies against heat shock proteins seem to be involved in the pathogenesis of coronary heart disease (CHD). We conducted a case-control study to investigate whether antibodies against Helicobacter pylori heat shock protein 60 (hsp60) are associated with CHD, and focused specifically on markers of systemic inflammation and lipids. METHODS: all patients of German nationality aged 40-68 years who underwent coronary angiography at the University of Ulm between October 1996 and November 1997 and who had at least one coronary stenosis greater than 50% were included in the study. Controls were sampled from voluntary blood donors and were matched for sex and age. H. pylori hsp60 was assessed by Western blot (H. pylori Westernblot, AID Co., Strassberg, Germany). In addition, C-reactive protein, fibrinogen, plasma viscosity, leukocytes, HDL-cholesterol and Lp(a) were determined. RESULTS: overall, 312 patients and 479 controls were enrolled in the study (response in patients 78%, in controls 84%). Whereas 25.0 and 22.4% of the cases showed a hsp60 extinction of 100 or 20-99% (according to the reference blot), respectively, only 21.3 and 14.8% of the controls did so (P=0.004). The age and sex adjusted odds ratio (OR) for CHD was 1.53 (95% confidence interval (CI) 1.14-2.06) given an extinction of 20-100% compared with an extinction of 0-19%. The OR for CHD decreased to 1.28 (95% CI 0.90-1.81) after further adjustment for other covariates. With exception of HDL-cholesterol (lowest in subjects with the highest hsp60 extinction) none of the investigated inflammatory markers was associated with the hsp60 distribution. CONCLUSION: a high H. pylori hsp60 extinction seems not to be an independent risk factor for CHD in this population.

Adult↗
PubMed2001

A novel TC deletion resulting in Pro(260)-->Stop in the human LCAT gene is associated with a dominant effect on HDL-cholesterol.

Human lecithin:cholesterol acyltransferase (LCAT) plays a key role in the biogenesis of circulating high-density lipoprotein-cholesterol (HDL-C) and reverse cholesterol efflux. We investigated the molecular defect in the LCAT gene in a family with low levels of HDL-C. The proband, a 53-year-old woman from Oklahoma City, had a HDL-C level of 0.21 mmol/l. The LCAT activity in the proband was 5 nmol/ml/h and cholesterol esterification rate was 54.2 nmol/ml/h, consistent with LCAT deficiency. Analysis of polymerase chain reaction (PCR) amplified subgenomic fragments of LCAT DNA on polyacrylamide gels revealed heteroduplex bands in the proband and three other affected individuals in exon 6. DNA sequence analyses of the proband's LCAT gene identified a 2 base pair deletion (TC) (base pairs 4544-4545, corresponding to amino acid 255) in the heteroduplex allele, thereby converting Pro(260) to a premature stop codon and a predicted truncated protein of 260 amino acids. This is approximately 60% of the length of the normal translated protein. The heterozygous individuals also revealed significant reduction in apolipoprotein A-1 levels compared with the unaffected family members (n=4). The marked reduction in HDL-C in the proband and sibling suggests a dominant effect of this mutation on HDL-C levels. Furthermore, because the deletion results in a heterozygous allele that can be detected by a simple PCR reaction and polyacrylamide gel-size fractionation, it may be possible to rapidly screen susceptible individuals for the presence of this mutation.

Base Sequence↗
PubMed2001

Inverse association between sense of humor and coronary heart disease.

Prospective studies have suggested that antisocial Type A personality traits may be associated with an increased incidence of coronary heart disease (CHD). However, few data have addressed whether more favorable personality characteristics may be inversely correlated with CHD. Therefore, two standardized questionnaires designed to either assess anger and hostility or to measure the propensity to laugh under a variety of situations encountered in everyday life, were administered to 300 consecutive subjects. Compared to controls, CHD subjects were significantly less likely to experience laughter during daily activities, surprise situations or social interactions (P<0.005). Logistic regression analysis revealed an inverse correlation between humor and CHD, even after adjustment for other covariates, including hypercholesterolemia, hypertension and diabetes mellitus (P=0.03). A significant inverse association was also observed between humor production and antisocial Type A personality traits (P=0.0001). These data extend previous observations linking antisocial Type A personality traits to CHD and raise the possibility that the propensity to laugh may contribute to cardioprotection.

Analysis of Variance↗
PubMed2001

Networks, resources and risk among women who use drugs.

The public health tradition of intervening at the environmental level has not been fully exploited in terms of HIV prevention efforts among drug users. Women who use drugs are at particularly high risk of acquiring HIV and other blood borne and sexually transmitted infections, such as hepatitis B (HBV) and hepatitis C (HCV), and could potentially benefit from environmental level interventions. In a review of the existing literature, we examine the extent to which the linkages among multiple causal levels may contribute to the disease transmission risk experienced by women who use drugs. The multiple causal levels of risk potentially involved in the transmission dynamics of infectious pathogens include biological, behavioral, dyadic relationship, network, and structural levels. Biological and behavioral risk factors have already been examined in depth; yet, little empirical research currently exists for other causal levels. Increasingly, investigators suggest that the character and dynamics of relationships with sex partners may be an important determinant of risk, both for engaging in risk behaviors and for doing so with high-risk partners. The influence of higher-order causal level factors, specifically network and structural factors, are the least well documented, but are posited to be a principal underlying cause of the current differential HIV incidence rates between men and women who use drugs. Future research should focus on these higher-order causal levels, in order to better understand disease transmission dynamics; to better evaluate the limitations, as well as the opportunities, of current intervention efforts; to develop interventions that improve and supplement current HIV prevention efforts among women who use drugs; and to inform public policy debate.

Adult↗
PubMed2001

Syndromes of excess antidiuretic hormone release.

Hyponatremia, particularly that due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), is common in patients seen in the critical care setting. Because of aging-associated changes in the hormonal and renal systems involved in regulation of water and sodium balance, older persons are at higher risk than the young. The high prevalence of disease states and drug use in the elderly can affect water and sodium conservation and further contribute to the risk of hyponatremia in this population. The approach to management is dependent both on the severity of hyponatremia-related symptoms and the rapidity with which hyponatremia has developed. Careful monitoring of serum sodium during treatment is essential to produce prompt resolution of symptoms while avoiding the development of central pontine myelinolysis. Several therapeutic modalities are available for the longterm management of chronic hyponatremia.

Acute Disease↗
PubMed2001

Systemic administration of immunostimulatory DNA sequences mediates reversible inhibition of Th2 responses in a mouse model of asthma.

This study investigated whether immunostimulatory DNA sequences (ISS) induce a transient or sustained inhibition of Th2 responses to inhaled antigen. We sensitized mice with subcutaneous injections to develop a Th2 response to ovalbumin (ova) and then administered a dose of ISS prior to ova inhalation challenge. Mice were then rechallenged with ova by inhalation a second time at varying time points after the first ova inhalation (1 to 8 weeks later) to determine whether the ISS dose administered prior to the first ova inhalation protected against a subsequent second ova inhalation challenge. A single dose of ISS inhibited the Th2 response to the first inhalation of ova antigen, as well as 4 weeks later to the second inhalation of ova. However, ISS did not inhibit a Th2 response to the second inhalation of ova 8 weeks later. The reversible inhibition of Th2 responses at 8 weeks suggests the need for repeated ISS administration at monthly intervals.

Adjuvants, Immunologic↗
PubMed2001

Overexpression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals.

In nuclear transgenic plants, expression of multiple genes requires introduction of individual genes and time-consuming subsequent backcrosses to reconstitute multi-subunit proteins or pathways, a problem that is compounded by variable expression levels. In order to accomplish expression of multiple genes in a single transformation event, we have introduced several genes into the chromoplast genome. We confirmed stable integration of the cry2Aa2 operon by PCR and Southern blot analyses in T(0) and T(1) transgenic plants. Foreign protein accumulated at 45.3% of the total soluble protein in mature leaves and remained stable even in old bleached leaves (46.1%), thereby increasing the efficacy and safety of transgenic plants throughout the growing season. This represents the highest level of foreign gene expression reported in transgenic plants to date. Insects that are normally difficult to control (10-day old cotton bollworm, beet armyworm) were killed 100% after consuming transgenic leaves. Electron micrographs showed the presence of the insecticidal protein folded into cuboidal crystals. Formation of crystals of foreign proteins (due to hyperexpression and folding by the putative chaperonin, ORF 2) provides a simple method of purification by centrifugation and enhances stability by protection from cellular proteases. Demonstration of expression of an operon in transgenic plants paves the way to engineering new pathways in plants in a single transformation event.

Animals↗
PubMed2001

Gender differences in syringe exchange program use in Oslo, Norway.

AIMS: To examine gender differences in syringe exchange program (SEP) use, particularly frequent SEP use, within and across survey years. DESIGN: Three consecutive, anonymous cross-sectional surveys. SETTING: The SEP in Oslo, Norway. PARTICIPANTS: Two hundred and eighty-eight, 449 and 523 SEP participants interviewed during comparable 1-week periods in 1992, 1994 and 1997, respectively. MEASUREMENTS: Brief structured questionnaires assessed SEP use, HIV risk behaviors and self-reported HIV status. Chi square statistics, t-tests and analysis of variance were used to identify gender differences; logistic regression was used to identify independent correlates of frequent SEP use. FINDINGS: Women reported injecting more frequently than men, but neither reported more frequent SEP use nor acquiring more syringes during an exchange. Although syringe sharing decreased significantly over time, in 1997, 51% of SEP participants continued to share. HIV prevalence remained low (3-5%) over time. After controlling for gender, age and HIV risk factors, frequent SEP use was significantly correlated with frequent injection for both women (OR = 1.4) and men (OR = 1.5). A lack of income or benefits independently increased the likelihood of being a frequent SEP user (OR = 3.0), while having shared a syringe at last injection independently decreased this likelihood (OR = 0.5). CONCLUSIONS: Gender was not associated with frequent SEP use; rather, the single most important correlate of frequent SEP use was injection frequency. Women's need for sterile syringes may not be fully addressed, despite the existence of a well-established and well-utilized SEP.

Adolescent↗
PubMed2001

Potential risk factors for the transition to injecting among non-injecting heroin users: a comparison of former injectors and never injectors.

AIMS: To compare potential risk factors for the transition to injecting among non-injecting heroin users (NIUs) with different injecting histories. DESIGN: Cross-sectional data from baseline structured interviews with NIUs in a study on transitions to injecting. Sample recruited by outreach or chain-referral in New York City (NYC), 1996-1998. SETTING: Recruitment of sample and interviews conducted in a NYC neighborhood where many drug users reside and/or use drugs. PARTICIPANTS: Of 575 NIUs, 67% had never injected; 16% had injected one to nine times (infrequent former injectors (IFI)); and 18% 10 or more times (frequent former injectors (FFI)). MEASUREMENTS: Controlling for age and race/ethnicity, adjusted odds ratios were estimated in multivariate logistic regression, and differences in means tested by ANCOVA. FINDINGS: FFI (compared to never injectors and IFI) were more likely: to be homeless; to be unemployed; to be long-time users; to be younger at first heroin use; to not have initiated heroin use through non-injected routes; to not be afraid of injecting themselves with needles; to sniff heroin with former IDUs; and, for both men and women separately, to have sex partners who were former IDUs. Both FFI and IFI were twice as likely as never injectors to perceive that their friends thought that it was "OK" to inject drugs. CONCLUSIONS: FFI have multiple individual and network characteristics that may increase their risk of injecting drugs. Interventions among NIUs to prevent transitions to injecting need to ascertain NIUs' injecting history and address the many potential risks that FFI have for resuming injecting drug use.

Adolescent↗
PubMed2001

Behaviour problems in extremely low birthweight children at 5 and 8 years of age.

This study explored the prevalence and stability of behaviour problems and their prediction from neonatal, medical and family context factors in a group of extremely low birthweight (ELBW) infants assessed at 5 and 8 years of age. Behaviour problems were identified on the basis of several measures: the Total Behaviour Problem Scale and the Adaptive Function Scale of the Child Behaviour Checklist, and the Hyperactivity Index and Hyperactivity Scale from the Conners' Rating Scale. In this group of ELBW infants, the prevalence of behaviour difficulties was somewhat lower than that reported in other studies, and varied according to the measure and informant (parent vs. teacher) used. Also, there was little continuity between those children identified by their parents at 5 years of age as having behaviour problems and those children identified by parent and/or teacher report at 8 years of age. Most of the children identified with behaviour difficulties at 8 years were also reported to have academic difficulties. None of the neonatal or medical factors predicted behaviour difficulties at 8 years of age. In contrast, two family context factors, maternal level of education and family stress, were related to behaviour difficulties at 8 years. These findings indicate that ELBW and the often associated medical complications may not necessarily predispose infants to develop subsequent behaviour difficulties later on in childhood.

Adult↗
PubMed2001

A stop codon in xeroderma pigmentosum group C families in Turkey and Italy: molecular genetic evidence for a common ancestor.

Xeroderma pigmentosum family G from Van, Turkey had two severely affected children: a son with multiple skin cancers who died at age 10 (XP67TMA), and an 8 y old daughter who began developing skin cancer before 3 y of age (XP68TMA). XP67TMA and XP68TMA cells were hypersensitive to killing by ultraviolet and the post-ultraviolet DNA repair level was 12-16% of normal. Host cell reactivation of an ultraviolet-treated reporter plasmid cotransfected with a vector expressing wild-type XPC cDNA assigned XP67TMA to xeroderma pigmentosum complementation group C. The XPC mRNA level was markedly reduced. Sequencing of the 3.5 kb XPC cDNA from XP67TMA showed a C-T mutation in XPC exon 8 at base pair 1840. This mutation converts the CGA codon of arginine at amino acid 579 to a UGA stop codon resulting in marked truncation of the 940 amino acid xeroderma pigmentosum C protein. Restriction fragment length polymorphism analysis of XPC exon 8 DNA in XP67TMA and XP68TMA showed that both affected children had a homozygous mutation and that both parents had heterozygous normal and mutated sequences at the same position consistent with a history of consanguinity in the family. The mutated allele also contained two XPC single nucleotide polymorphisms. The same mutated XPC allele was reported in an Italian family. Studies of 19 microsatellite markers flanking the XPC gene on chromosome 3 suggest that the XPC allele passed between Italy and Turkey approximately 300-500 y ago. This XPC allele containing a nonsense mutation is associated with severe clinical disease with multiple skin cancers and early death.

Adult↗
PubMed2001

Advancing age and cervical cancer screening and prognosis.

OBJECTIVES: To determine associations between advancing age and screening behavior and prognosis in long-term members of a prepaid health plan diagnosed with invasive cervical cancer (ICC). DESIGN: Case series. SETTING: Prepaid health plan. PARTICIPANTS: All women diagnosed with ICC at Kaiser Permanente Medical Care Program-Northern California health plan from 1988 to 1994. MEASUREMENTS: From medical records, we recorded participants' age, stage at diagnosis, tumor histology, and results of and reasons for all previous cervical smears. We limited our analysis to women who had been members of the health plan for at least 30 of the 36 months preceding diagnosis (n = 455). RESULTS: Women in older age groups were less likely than younger women to have been screened within the 3 years before diagnosis (P = .005 for trend). Nonadherence to follow-up of abnormal cervical smears was uncommon (17/455, 3.7%) and not age related (P = .932 for trend). The proportions of ICC that were interval cancers, defined as ICC diagnosed within 3 years of a negative screening smear, were highest in women under age 30 (P = .004 for trend). In multivariate analyses controlling for stage at diagnosis, women age 60 and older were not more likely to die of ICC within 3 years of diagnosis than were women younger than age 60 (odds ratio 1.30, 95% confidence interval 0.75-2.28). CONCLUSION: The disproportionate burden of cervical cancer observed in older women appears to be largely attributable to lack of screening within the 3 years before diagnosis.

Adenocarcinoma↗