Genome scan for quantitative trait loci linked to high-density lipoprotein cholesterol: The NHLBI Family Heart Study.

We conducted a genome-wide linkage scan for quantitative trait loci influencing total HDL-cholesterol (HDL-C) concentration in a sample of 1027 whites from 101 families participating in the NHLBI Family Heart Study. To maximize the relative contribution of genetic components of variance to the total variance of HDL-C, the HDL-C phenotype was adjusted for age, age(2), body mass index, and Family Heart Study field center, and standardized HDL-C residuals were created separately for men and women. All analyses were completed by the variance components method, as implemented in the program GENEHUNTER using 383 anonymous markers typed at the NHLBI Mammalian Genotyping Service in Marshfield, Wis. Evidence for linkage of residual HDL-C was detected near marker D5S1470 at location 39.9 cM from the p-terminal of chromosome 5 (LOD=3.64). Suggestive linkage was detected near marker D13S1493 at location 27.5 cM on chromosome 13 (LOD=2.36). We conclude that at least 1 genomic region is likely to harbor a gene that influences interindividual variation in HDL cholesterol.

Genome-wide linkage analysis of lipids in the Hypertension Genetic Epidemiology Network (HyperGEN) Blood Pressure Study.

Full genome scans were performed for quantitative lipid measurements in 622 African American and 649 white sibling pairs not taking lipid-lowering medications who were ascertained through the Hypertension Genetic Epidemiology Network (HyperGEN) of the National Heart, Lung, and Blood Institute (NHLBI) Family Blood Pressure Program. Genotypes for 391 markers spaced roughly equally throughout the genome were typed by the NHLBI Mammalian Genotyping Service. Each of the phenotypes was adjusted for covariates within sex and race and then subjected to variance components linkage analysis, which was performed separately within race by using race-specific marker allele frequencies from additional random samples. The highest lod score detected was 2.77 for logarithmically transformed triglyceride (TG) on chromosome 20 (at 28.6 cM) in the African American sibling pairs. The highest score detected in the white sibling pairs was 2.74 for high density lipoprotein cholesterol on chromosome 5 (at 48.2 cM). Although no scores >3.0 were obtained, positive scores were found in several regions that have been reported in other genome scans in the literature. For example, a score of 1.91 for TG was found on chromosome 15 (at 28.8 cM) in white sibling pairs. This score overlaps the positive findings for TG in 2 other genome scans.

Plasma fibrinogen and incident hypertension in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Several cross-sectional studies have reported a positive association between plasma fibrinogen levels and prevalent hypertension. Other studies have reported a positive association between hypertension and whole-blood or plasma viscosity, to which fibrinogen contributes. To our knowledge, there has been no prospective study of fibrinogen and incident hypertension. SUBJECTS AND METHODS: We measured plasma fibrinogen levels in a population-based cohort study of middle-aged adults and related it to the occurrence of incident hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg or use of antihypertensive medication) over 6 years. RESULTS: There was a moderately strong positive association between fibrinogen levels and prevalent hypertension in both men and women, with the odds of hypertension elevated by 50% for the highest fibrinogen quartile versus the lowest. Among 7884 participants at risk, 1609 developed hypertension over 6 years. Adjusted for age, race, field center and baseline systolic blood pressure, the odds ratio of incident hypertension in relation to fibrinogen quartiles was 1.0, 1.07, 1.21 and 1.43 in men (P= 0.003 for trend) and 1.0, 0.92, 0.99 and 0.99 in women (P= 0.89 for trend). After adjustment for other risk factors, the odds ratios were 1.0, 1.03, 1.15 and 1.29 (P= 0.045 for trend) in men and remained nonsignificant in women. CONCLUSIONS: Despite a moderately strong positive association between fibrinogen levels and prevalent hypertension in both sexes, there was only a weak positive association between fibrinogen levels and incident hypertension in men and no association in women. Whether an elevated fibrinogen level is a risk factor for, or a consequence of, hypertension remains unclear.

Association of C-reactive protein with markers of prevalent atherosclerotic disease.

Recent prospective studies have demonstrated that elevated C-reactive protein (CRP) is a marker of increased risk of atherothrombotic clinical events. We examined in a large, cross-sectional family-based study (n = 875 men, 948 women) whether serum CRP was associated with prevalent coronary heart disease (CHD), the ankle/brachial blood pressure index, or carotid intima-media thickness, an indicator of subclinical atherosclerosis as assessed by B-mode ultrasound. CRP was associated with many other cardiovascular risk factors, particularly markers of obesity and insulin resistance, markers of inflammation and acute phase reaction, and hormone replacement therapy. Adjusted for age and family type, there was a weak positive association of CRP with carotid intima-media thickness in both genders and with prevalent CHD in women. However, adjustment for other risk factors completely eliminated the associations. For example, among women, the risk factor-adjusted mean values of intima-media thickness across quartiles of CRP were 0.76, 0.74, 0.75, and 0.76 mm (p >0.5). In men there was a weak inverse association between CRP and ankle/brachial blood pressure index, independent of other risk factors, but no such association in women. Our findings indicate that CRP is not strongly and independently associated with prevalent atherosclerosis. Because CRP has been associated with clinical events, it could be that elevated CRP may be a stronger marker of thrombotic risk than of the degree of atherosclerosis.

Relationship of serum and dietary magnesium to incident hypertension: the Atherosclerosis Risk in Communities (ARIC) Study.

PURPOSE: To examine the relationship of serum and dietary magnesium (Mg) with incident hypertension. The setting was the Atherosclerosis Risk in Communities (ARIC) Study, which included a biracial cohort, aged 45-64 years, from four U.S. communities. METHODS: This analysis included 7731 participants (4190 women and 3541 men) free of hypertension at baseline and followed six years. Fasting serum Mg was measured, and usual dietary intake was assessed with a food frequency questionnaire. RESULTS: After adjustment for age, race, and a number of other risk factors, the odds of incident hypertension across ascending quartiles of serum Mg were 1.0, 0.79, 0.85, and 0.70 in women (p trend = 0.01) and 1.0, 0.87, 0.87, and 0.82 in men (p trend = 0.16). We found no association between dietary Mg intake and incident hypertension. These associations were attenuated after the addition of baseline systolic blood pressure to the models. CONCLUSIONS: This study suggests that low Mg may play a modest role in the development of hypertension.

Effects of potassium ions on action potential conduction in A- and C-fibers of rat spinal nerves.

Potassium ions in dentifrices for treating 'hypersensitive' dentin are believed to act directly on intradental nerves by raising extracellular potassium ion concentration ([K+]o) sufficiently to prevent action potential generation by axonal accommodation. However, the [K+]o necessary to block nerve conduction is not precisely known, nor is it certain that K+ can diffuse from a dentifrice in sufficient amounts to inactivate intradental nerves. To establish more accurately the [K+]o required to block nerve conduction under controlled conditions, we studied the effects of increased [K+]o on the sizes of compound action potentials (CAP) recorded from rat spinal nerves in vitro. [K+]o was increased by the addition of either KCl or KNO3 to Krebs' solutions applied to the central portion of the nerves. CAP attenuation increased in a dose-dependent manner as [K+]o was raised in the 8 to 64 mmol/L range, and complete block was generally produced with solutions containing at least 32 mmol/L K+. CAP attenuation was reversible, and recovery times increased with increasing [K+]o. The effects of KCl and KNO3 solutions were the same for all [K+]o tested. Half-maximal (50%) reduction in the A beta-fiber component of the CAP occurred with 17.4 mmol/L K+, and with 17.8 mmol/L and 19.3 mmol/L K+, respectively, for the A delta- and C-fiber components. Control experiments with glucose and choline chloride confirmed that the conduction block observed with increased [K+]o was not due to increased solution osmolarity or ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting nerve excitability and conduction as a basis for desensitizing dentine.

Nerve excitability is principally determined by the state of membrane sodium channels, which can be influenced by factors such as drugs or the ionic composition of the extracellular fluids. The excitability of isolated nerves is increased by lowered extracellular calcium and hydrogen ion concentrations, and similar effects are seen on intradental nerve excitability. This is of interest as some agents used to desensitize hypersensitive dentine are believed to act by reducing intradental nerve excitability. A variety of ions, including potassium and divalent cations, have been shown to reduce intradental nerve excitability when applied in relatively high concentrations to dentine close to the pulp. However, these conditions do not mimic the clinical situation, where agents are applied to outer dentine, up to 2 mm from the pulp. Also, when agents are applied to dentine it is difficult to quantify the precise changes in extracellular fluid composition, and there is the additional complication of possible interactions between the agents and dentine. These problems can be minimized by using isolated nerves, which allow better control over the conditions and ionic concentrations necessary to achieve nerve conduction block. Such methods can provide a convenient way to screen potential desensitizing agents before evaluation in vivo or in clinical trials.

Effects of pulsed Nd:YAG laser radiation on action potential conduction in nerve fibres inside teeth in vitro.

OBJECTIVE: This study aimed to simulate the effects of lasing dentine on pulpal nerve function. METHODS: Rat spinal nerve roots were threaded through the prepared pulp canal of a 10 mm long tooth root segment which was mounted in a perspex bath. The protruding ends of the nerve were placed on platinum wire electrodes used to elicit and to record compound nerve action potentials (CAPs). Laser energy (average power = 0.3-3.0 W) was applied to the surface of the root segment using a pulsed Nd:YAG dental laser (dLase 300). RESULTS: With the laser probe tip placed in static contact with the tooth surface, the nerve CAP was irreversibly abolished within 60 s of lasing at 1.0-3.0 W power. When the laser tip was moved to and fro over the root surface in a scanning mode, similar levels of radiation produced less marked effects. In the latter mode, CAP attenuation increased with increasing power and duration of lasing. After 60 s lasing at 0.3 W, the CAP size was 95% (+/- 5, S.D.) of the prelasing controls value; with 2.0 W the CAP was reduced to 54% (+/- 33). The CAP recovered to 90% of control levels after lasing at powers up to 1.5 W, but reached only 72% of control values after lasing at 2.0 W power. CONCLUSIONS: Laser radiation applied to dentine caused a dose-dependent block of action potential conduction in nerve fibres in the underlying pulp chamber.

Metabolic syndrome and risk of venous thromboembolism: Longitudinal Investigation of Thromboembolism Etiology.

SUMMARY BACKGROUND: In a recent case-control study, the odds of metabolic syndrome (MetSyn) among deep vein thrombosis cases were almost twice those among controls. We tested the hypothesis that the incidence of non-cancer-related venous thromboembolism (VTE) is higher among adults with MetSyn and further, that associations are stronger for idiopathic than secondary VTE. METHODS: A total of 20 374 middle-aged and elderly adults were followed for over 12 years for incident VTE in the Longitudinal Investigation of Thromboembolism Etiology (LITE). All hospitalizations were identified and VTEs validated by chart review. Baseline MetSyn was defined using ATP III guidelines, including >or=3 of the following components: abdominal obesity, elevated blood pressure, low HDL-cholesterol, high triglycerides and high glucose. Because sex modified the relation between MetSyn and VTE (p(interaction) = 0.001), proportional hazards regression analyses were stratified by sex to assess the associations of MetSyn and its components with risk of incident non-cancer-related VTE, adjusting for potential confounders. RESULTS: Incident VTE (n = 358) included 196 idiopathic events. Baseline MetSyn was associated with risk of total VTE (hazard ratio (HR) = 1.84, 95% CI = 1.30, 2.59) and idiopathic VTE (HR = 1.59, 95% CI = 1.02, 2.47) among men, but not women. The association was largely attributable to abdominal obesity (HR of VTE = 2.10, 95% CI = 1.51, 2.93, in men; HR of VTE = 1.70, 95% CI = 1.24, 2.34, in women), with no additional contribution by the other MetSyn components. CONCLUSION: Although abdominal obesity was associated with increased risk of VTE in both men and women, MetSyn and its other components do not seem important in VTE etiology.

Action potential conduction block of nerves in vitro by potassium citrate, potassium tartrate and potassium oxalate.

OBJECTIVES: Potassium salts in desensitising formulations are believed to act by blocking nerve conduction. The aim of this study was to assess the ability of some organic potassium salts to block action potential conduction and to compare their effects with potassium chloride and potassium nitrate. MATERIALS AND METHOD: Potassium citrate, oxalate or tartrate were added to Krebs' solutions to raise the potassium concentration to 8-64 mM. The test solutions were applied to rat spinal nerves in a bath while monitoring the compound action potentials evoked by electrical stimulation. RESULTS: All potassium salts attenuated the compound action potential in a dose-dependent manner. There were no significant differences between the effects of potassium tartrate and potassium citrate solutions (p>0.1) which caused significantly greater compound action potential attenuation than the same concentrations of potassium oxalate (p<0.05). On the basis of the potassium ion concentration required to cause 50% attenuation of the compound nerve action potential, the relative potencies of the potassium salts were: citrate = tartrate> oxalate>chloride =nitrate. CONCLUSION: Potassium citrate and potassium tartrate were more effective than other potassium salts in blocking nerve conduction and may be more effective dentinal desensitising agents.

Hand infections in patients with diabetes mellitus.

In a study of diabetic patients with hand infections reviewed at Jackson Memorial Hospital, University of Miami School of Medicine, 20 such diabetic patients with hand infections were found. The most outstanding result was that seven of the 20 had amputation either to control infection or because the function of the extremity was impaired by the remaining ravaged part. Pathologic examination of tissue removed showed the same changes commonly seen in diabetic gangrene of the lower extremity. Electromyographic studies, when done, have been confirmatory of a peripheral neuropathy with delayed nerve conduction studies. The bacterial organisms of the infections were variable, but a predominance of Gram-negative organisms were cultured in twelve of the 20 patients. Early aggressive management, including surgical debridement and intravenous antibiotics, is recommended to prevent unnecessary amputations and improve residual function.

Effect of pulsed Nd:YAG laser radiation on action potential conduction in isolated mammalian spinal nerves.

BACKGROUND AND OBJECTIVE: Dental lasers are claimed to produce analgesia, but the mechanisms and extent of any effects are uncertain. This study investigated the effects of lasing on nerve conduction in isolated nerves. STUDY DESIGN/MATERIALS AND METHODS: Pulsed Nd:YAG laser energy was applied to spinal nerves in vitro and effects were measured as attenuation of the compound action potential (CAP) evoked by electrical stimulation. RESULTS: Lasing for 1 minute at 0.3-3.0 W caused a dose-dependent attenuation of all components of the CAP (P < 0.03). With 0.3-1.0 W power, the CAP recovered to > 95% of the control levels 7 minutes after lasing; recovery was incomplete after lasing at > 2.0 W. CONCLUSION: Isolated nerves were remarkably tolerant of lasing. The degree of nerve conduction block increased with laser power. The data indicate that lasing could diminish sensations, including pain, mediated by peripheral nerves in soft tissues.

Association of nonsteroidal anti-inflammatory drugs and aspirin with cognitive performance in middle-aged adults.

OBJECTIVES: To assess the cross-sectional association of regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with cognitive function in 13,153 individuals, aged 48-67 years, participating in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Regular use of NSAIDs or aspirin was analyzed in relation to the results of three cognitive tests, the Delayed Word Recall Test, the WAIS-R Digit Symbol Subtest, and the Word Fluency Test. RESULTS: After adjustment for covariates previously found to be associated with cognition in this sample, we found a weak negative association between current use of aspirin and poor Word Recall [OR = 0.84 (95% confidence interval: 0.68-1.04)] and poor Word Fluency [OR = 0.85 (0.70-1.03)]. We found no association between current use of aspirin and Digit Symbol score, nor did we find current NSAID use to be significantly associated with any of the cognitive tests. CONCLUSIONS: This study suggests a modest association, at best, between NSAIDs or aspirin and better cognitive function.

Dietary antioxidant intake and cognitive performance in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study investigators.

OBJECTIVE: To assess the cross-sectional association of dietary and supplemental antioxidant (carotenoids, vitamins C and E) intake with cognitive function in 12 187 individuals, aged 48-67 years, participating in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: Dietary intake of antioxidant vitamins, as assessed by a food frequency questionnaire, and use of supplements were analysed in relation to the results of three cognitive tests, the delayed word recall test, the Wechsler adult intelligence scale, revised (WAIS-R) digit symbol subtest and the word fluency test. RESULTS: After adjustment for covariates previously found to be associated with cognition in this sample, we found no consistent associations between dietary antioxidant vitamin intake or supplement use and any of the cognitive tests. CONCLUSIONS: This study suggests little, if any, association between antioxidant vitamin intake and better cognitive function in middle-aged adults.