Biomedical subjects

R R Williams

Publications and source records attributed to R R Williams.

At least 19 recordsLinked to original sources

PubMed2003

Mineral uptake in tobacco leaf discs during different developmental stages of shoot organogenesis.

Relationships between mineral uptake and tobacco shoot organogenesis were investigated during three morphogenic phases: phase 1, days 0-10, pre-meristem formation; phase 2, days 10-20, meristem initiation and formation; and phase 3, days 20-35, growth and differentiation of induced meristems into leafy shoots. The mineral content of both shoot-forming (SF) and non-shoot-forming (NSF) media was examined over the 35-day culture period. Both SF and NSF explants rapidly consumed iron during phase 1. Nitrate uptake in SF explants was high and independent of explant growth during phases 1 and 2, but greatest and strongly correlated with growth during phase 3. Phosphorus uptake was highest in SF explants during phases 2 and 3, and correlated with explant growth. Uptake of potassium, calcium and sulphur was strongly associated with explant growth during phase 3 whereas magnesium uptake was only poorly correlated with growth. Results from this study indicate that particular minerals may have an important role in regulating development as well as generally supporting growth.

Culture Media↗

PubMed2002

Absence of a pharmacokinetic interaction between digoxin and levofloxacin.

BACKGROUND: Levofloxacin, a broad-spectrum fluoroquinolone, may enhance digoxin bioavailability by eliminating intestinal flora that metabolize digoxin. Moreover, levofloxacin, which is eliminated primarily by glomerular filtration and active tubular secretion, may alter the elimination rate of digoxin. Because of the narrow therapeutic index of digoxin, it is important to evaluate the potential for interaction with levofloxacin when administered concomitantly. METHODS: This was a placebo-controlled, randomized, double-blind, two-phase crossover study. Twelve healthy subjects (six males and six females) received 500 mg twice/day oral doses of levofloxacin or placebo for 6 days and a single oral dose of 0.4 mg digoxin on the morning of study day 5 along with levofloxacin or placebo. RESULTS: There was no significant effect of levofloxacin on the pharmacokinetics (Cmax, AUC, and other disposition parameters) of oral digoxin. Steady-state levofloxacin absorption and disposition kinetics were also similar in the presence or absence of digoxin. CONCLUSIONS: Results of this study suggest that an important pharmacokinetic interaction between levofloxacin and digoxin is unlikely to occur when administered concomitantly.

Administration, Oral↗

PubMed2002

Penetration of levofloxacin into skin tissue after oral administration of multiple 750 mg once-daily doses.

OBJECTIVE: To probe the pharmacokinetic basis for the use of levofloxacin for complicated skin and skin-structure infections (SSSIs) at a once-daily dosage of 750 mg by investigating its penetration into skin tissue. METHOD: Ten healthy volunteers were administered three oral, once-daily 750 mg doses of levofloxacin, and levofloxacin concentrations were subsequently measured over time (0.5-24 h) in skin-punch biopsy tissue and plasma. RESULTS: Skin tissue concentrations consistently exceeded those in plasma at every time point, with tissue/plasma ratios of 1.37 +/- 0.81 for peak concentration and 1.97 +/- 0.35 for area under the concentration versus time curve. Three of the ten subjects reported treatment-emergent adverse events (AEs) that were considered unrelated to treatment. An 11th subject who had enrolled in the study withdrew after AEs of mild severity that were possibly related to the study drug. CONCLUSION: The results support the clinical usage of levofloxacin 750 mg once-daily for complicated SSSIs.

Administration, Oral↗

PubMed2001

The minisatellite of the GPI/AMF/NLK/MF gene: interspecies conservation and transcriptional activity.

Minisatellites are tandemly repeated DNA sequences found throughout the genomes of all eukaryotes. They are regions often prone to instability and hence hypervariability; thus repeat unit sequence is generally not conserved beyond closely related species. We have studied the minisatellite located in intron 9 of the human glucose phosphate isomerase (GPI) gene (also known as neuroleukin, autocrine motility factor, maturation and differentiation factor) and have found, by Zoo blotting coupled with PCR amplification and DNA sequencing, that similar repeat units are present in seven other species of mammal. There is also evidence for the presence of the minisatellite in chicken. The repeat unit does not appear to be present at any other locus in these genomes. Minisatellite DNA has been reported to be involved in recombination activity, control of gene expression of nearby gene(s) (both transcriptional and translational), whilst others form protein coding regions. The high level of conservation exhibited by the GPI minisatellite, coupled with the unique location, strongly suggests a functional role. Our results from transient and stable transfections using luciferase reporter constructs have shown that the GPI minisatellite region can act to increase transcription from the SV40 promoter, CMV promoter and the human GPI promoter.

Animals↗

PubMed2001

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Adult↗

PubMed2001

Frequency of the R3500Q mutation of the apolipoprotein B-100 gene in a sample screened clinically for familial hypercholesterolemia in Hungary.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) cause early onset of coronary heart diseases (CHD). According to the recommendations of the international MEDPED program, we tried to find FH cases. We analyzed 73 FH probands and their 304 first-degree relatives. A total of 39 probands were found from the 21000 subjects screened (1:538) from family doctors' registers recording all citizens, while the remaining 34 were derived from screened patients from lipid clinics. In our FH probands, four cases of FDB (R3500Q mutation) were diagnosed with allele-specific PCR, and the mutation was also detectable in five cases out of seven living family members. In the remaining 69 FH families, 156 people were diagnosed clinically with FH, and 31.8% of the males (against 13% of the not clinically diagnosed FH males, P<0.01), and 32.4% of the females (against 13.5% of the not clinically diagnosed FH females, P<0.01) suffered from early onset CHD. The plasma total cholesterol level of the FDB patients, especially in the younger patients, was very close to normal values. Therefore, the FDB patients seem to be under-represented in this type of survey. Because FDB is one of the independent causes of early onset CHD, the R3500Q mutation should be considered in families with a high frequency of cardiovascular diseases.

Adolescent↗

PubMed2001

Effectiveness of levofloxacin for adult community-acquired pneumonia caused by macrolide-resistant Streptococcus pneumoniae: integrated results from four open-label, multicenter, phase III clinical trials.

BACKGROUND: The rate of macrolide resistance among Streptococcus pneumoniae clinical isolates is rising. Coresistance to several unrelated classes of antimicrobial agents is common and may limit the treatment options available for the management of infections caused by this pathogen. Although the fluoroquinolones appear to retain activity against macrolide-resistant pneumococci, limited clinical data exist to support their use in this setting. OBJECTIVE: This study integrated data from 4 clinical trials to determine whether the fluoroquinolone levofloxacin is an effective therapeutic agent for community-acquired pneumonia (CAP) caused by macrolide-resistant S. pneumoniae. METHODS: Across the 4 trials, 271 adult patients with CAP were diagnosed with infections caused by S. pneumoniae; these constituted the intent-to-treat population. Clinical isolates obtained from each patient at admission were tested using broth microdilution for in vitro sensitivity to the macrolide erythromycin (minimum inhibitory concentration breakpoints: susceptible, < or =0.25 microg/mL; intermediate, 0.5 microg/mL; resistant, > or =1.0 microg/mL). All patients received levofloxacin (500 mg once daily for 7-14 days) and were analyzed at a posttherapy visit (2-5 days after completion of therapy) for clinical and microbiologic outcomes; in 3 trials, patients were also examined at a poststudy visit (14-28 days after completion of treatment). Clinical and microbiologic outcomes were analyzed in patients infected with macrolide-resistant and macrolide-susceptible S. pneumoniae. RESULTS: A total of 235 evaluable patients infected with S. pneumoniae were identified from the 4 trials. Twenty-seven (11.5%) patients were infected with isolates resistant to erythromycin, of whom 26 (96.3%) were clinical successes. By comparison, the clinical success rate in patients infected with erythromycin-susceptible isolates was 97.7%. CONCLUSIONS: These results suggest that if future studies demonstrate the clinical relevance of macrolide resistance, levofloxacin may be a useful therapeutic option in patients with CAP caused by macrolide-resistant S. pneumoniae. However, caution may be warranted to prevent overprescription of levofloxacin and other fluoroquinolones, given the potential for the development of resistance in S. pneumoniae.

Anti-Bacterial Agents↗

PubMed2001

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Adult↗

PubMed2000

Co-segregation of elevated LDL with a novel mutation (D92K) of the LDL receptor in a kindred with multiple lipoprotein abnormalities.

Factors predisposing to the phenotypic features of familial combined hyperlipidemia have not been clearly defined. In the course of investigating familial coronary artery disease in Utah, we identified a three-generation family in which multiple members were affected with type IIa hyperlipoproteinemia (HLP IIa), type IIb hyperlipoproteinemia (HLP IIb), or type IV hyperlipoproteinemia (HLP IV). Because several family members had relatively severe low-density lipoprotein (LDL) cholesterol elevation, in order to dissect the possible contribution to the plasma lipoprotein abnormalities in this pedigree, we identified a novel point mutation in the low-density lipoprotein receptor (LDLR) gene, a G-to-A transition at nucleotide position 337 in exon 4. This change substituted lysine for glutamic acid at codon 92 (D92K) of the LDL receptor. By means of mutant allele-specific amplification we determined that the mutation co-segregated with elevated cholesterol and LDL cholesterol in the plasma of family members with HLP IIa and HLP IIb, but not with the elevated plasma triglycerides seen in HLP IIb and HLP IV patients. Thus, in families with apparent familial combined hyperlipidemia, a defective LDLR allele and other genetic or environmental factors that elevate plasma triglycerides may account for the multiple lipid phenotypes observed in this kindred.

Adult↗

PubMed2000

Plasma homocysteine and its association with carotid intimal-medial wall thickness and prevalent coronary heart disease: NHLBI Family Heart Study.

Mildly elevated plasma total homocysteine (tHcy) levels have been associated with increased risk of coronary heart disease (CHD). Carotid artery intimal-medial wall thickening is a predictor of cardiovascular disease and has been previously shown to be positively associated with plasma tHcy in studies of asymptomatic subjects. In the current study we examined 1467 subjects with regard to their fasting plasma tHcy levels and intimal-medial wall thickness as measured by B-mode ultrasound and early onset CHD. The results showed that there is a significant positive association between plasma tHcy levels and carotid-artery wall thickness in participants 55 years or older even after the tHcy levels are adjusted for age, smoking and anti-hypertensive medication. The direction and magnitude of the relationship is similar although the result was not statistically significant in younger participants ( < 55 years). Early onset CHD at any age was not significantly different across the tHcy quintiles. The lack of an association of tHcy and CHD in the presence of a positive association with intimal-medial wall thickening may be a reflection of increased statistical power of quantitative versus qualitative traits. We conclude that the present finding of a positive association between tHcy and intimal-medial wall thickness strengthens the in vitro finding of the stimulating effect of homocysteine on vascular smooth muscle cell growth. Vascular smooth muscle cell proliferation may be an important mechanism through which mildly elevated plasma tHcy promotes atherosclerosis.

Aged↗

PubMed2000

No evidence of linkage between the very-low-density lipoprotein receptor gene and fasting serum insulin or homeostasis model assessment insulin resistance index: the National Heart, Lung, and Blood Institute Family Heart Study.

A major gene effect on the fasting insulin level and insulin resistance has been suggested in previous studies. Several candidate genes for insulin resistance in rare syndromes have been proposed. However, there has been limited success in finding genes for common forms of insulin resistance. There is accumulating evidence of a relationship between insulin resistance and a disturbance of free fatty acid (FFA) metabolism. The very-low-density lipoprotein (VLDL) receptor, which is associated with FFA metabolism, could serve as a possible candidate gene for insulin resistance. We performed linkage analyses between the VLDL receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin x fasting glucose/22.5) in 1,050 sibpairs participating in the phase II physical examination of the National Heart, Lung, and Blood Institute Family Heart Study (FHS). Data analyses were completed using the SIBPAL component of the SAGE software package (SAGE, Statistical Analysis for Genetic Epidemiology, Version 3.1; Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 1997). We did not find evidence for linkage of the fasting insulin or the HOMA insulin resistance index with a polymorphic marker at the VLDL locus (P = .316 and .402, respectively). Adjustment of fasting insulin and the HOMA insulin resistance index for the body mass index (BMI) did not change the results (P = .319 and .472, respectively). In conclusion, no evidence was found for a linkage between a locus controlling the fasting insulin level or HOMA insulin resistance index and a VLDL polymorphism in the present study. Additional adjustment of fasting insulin or the HOMA insulin resistance index for the BMI did not change the linkage results significantly.

Blood Glucose↗

PubMed2000

Insulin and hypertension in the NHLBI Family Heart Study: a sibpair approach to a controversial issue.

The association between insulin and hypertension remains equivocal. We therefore investigated insulin levels in 3037 normotensive and 1067 hypertensive subjects from the National Heart, Lung and Blood Institute (NHLBI) Family Heart Study (FHS) by two different approaches. First, we compared insulin levels between normotensive and 275 untreated hypertensive subjects. Insulin levels unadjusted as well as adjusted for age, sex, and center were significantly higher in hypertensives. After adjustment for body mass index (BMI), insulin remained significantly higher only in the diastolic hypertensive group (mean +/- SD 77.0 +/-36.7 pmol/L, P < .01) but not in the isolated systolic hypertensive group (67.0 +/- 38.2 pmol/L) when compared to normotensives (63.2 +/- 29.1 pmol/L). A sibpair analysis was then used that compared the intra-sibpair differences in insulin concentrations to the intra-sibpair differences in blood pressure (BP) levels. This approach was intended to control for the effects of genetic and residual shared environmental variance upon insulin levels. The intra-sibpair difference in insulin concentrations between concordant (diastolic and systolic deltaBP < 5 mm Hg) and discordant sibpairs (diastolic and systolic deltaBP > 15 and > 20 mm Hg, respectively) was no longer significantly different when adjusted for BMI (2.7 v 5.9 pmol/L for diastolic and -1.7 v -1.8 pmol/L for systolic BP). Even the random selection of one sibpair from each of the 326 families independently of insulin and BP levels did not result in a significant correlation between the intrasibpair differences in insulin and BP. Using an insulin resistance index instead of insulin did not change our findings. Our investigation in the FHS sample of families suggests that there is only a small, if any, influence of insulin levels on BP after adjustment for obesity-related sources of variation.

Adult↗

PubMed2000

Association between the alpha-adducin gene and hypertension in the HyperGEN Study.

This report from the HyperGEN Study, one of four networks participating in the NHLBI-sponsored Family Blood Pressure Program, presents the results of an association study based on 822 white and 572 black subjects (cases and controls) participating in the HyperGEN Network from five geographically diverse field centers. All cases met the Joint National Committee on Detection and Treatment of High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each subject was clinically examined for risk factors for hypertension as well as genotyped for the point mutation Gly460Trp at the alpha-adducin locus on chromosome 4p. In the white group, the prevalence of genotypes with one or more Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly selected from the population, and 39% among the multiply affected hypertensive sibships. Overall, in whites, the Trp allele significantly increased the odds of hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant independent predictor of hypertension in a multivariate logistic model even after correcting for other risk factors for hypertension, including gender, age, body mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of regression trees, several gene-by-environment interactions were implicated, suggesting that alpha-adducin appears to be a particularly important risk factor (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black group, the relationship was less clear. Overall, it was protective against hypertension. The prevalence of genotypes with one or more Trp alleles was 24% among normotensive versus 11% in hypertensive black subjects randomly selected from the population, and 13% among multiply affected hypertensive sibships, resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp genotype was no longer a significant independent predictor of hypertension risk in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting that it may be operating through one or more of these other factors. Thus, we conclude that the alpha-adducin gene is a significant, independent risk factor for hypertension in whites, but not in blacks, and may play a particularly important role for subjects with certain constellations of other risk factors.

Alleles↗

PubMed2000

NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network.

PURPOSE: Hypertension is a common precursor of serious disorders including stroke, myocardial infarction, congestive heart failure, and renal failure in whites and to a greater extent in African Americans. Large genetic-epidemiological studies of hypertension are needed to gain information that will improve future methods for diagnosis, treatment, and prevention of hypertension, a major contributor to cardiovascular morbidity and mortality. METHODS: We report successful implementation of a new structure of research collaboration involving four NHLBI "Networks," coordinated under the Family Blood Pressure Program. The Hypertension Genetic Epidemiology Network (HyperGEN) involves scientists from six universities and the NHLBI who seek to identify and characterize genes promoting hypertension. Blood samples and clinical data were projected to be collected from a sample of 2244 hypertensive siblings diagnosed before age 60 from 960 sibships (half African-American) with two or more affected persons. Nonparametric sibship linkage analysis of over one million genotype determinations (20 candidate loci and 387 anonymous marker loci) was projected to have sufficient power for detecting genetic loci promoting hypertension. For loci showing evidence for linkage in this study and for loci reported linked or associated with hypertension by other groups, genotypes are compared in hypertensive cases versus population-based controls to identify or confirm genetic variants associated with hypertension. For some of these genetic variants associated with hypertension, detailed physiological and biochemical characterization of untreated adult offspring carriers versus non-carriers may help elucidate the pathophysiological mechanisms that promote hypertension. RESULTS: The projected sample size of 2244 hypertensive participants was surpassed, as 2407 hypertensive individuals (1262 African-Americans and 1145 whites) from 917 sibships were examined. Detailed consent forms were designed to offer participants several options for DNA testing; 94% of participants gave permission for DNA testing now or in the future for any confidential medical research, with only 6% requesting restrictions for tests performed on their DNA. Since this is a family study, participants also are asked to list all first degree relatives (along with names, addresses, and phone numbers) and to indicate for each relative whether they were willing to allow study staff to make a contact. Seventy percent gave permission to contact some relatives; about 30% gave permission to contact all first degree relatives; and less than 1% asked that no relatives be contacted. Successes after the first four years of this study include: 1) productive collaboration of eight centers from six different locations; 2) early achievement of recruitment goals for study participants including African-Americans; 3) an encouraging rate of consent for DNA testing (including future testing) and relative contacting; 4) completed analyses of genetic linkage and association for several candidate gene markers and polymorphisms; 5) completed genotyping of random markers for over half of the full sample; and 6) early sharing of results among the four Family Blood Pressure Program networks for candidate and genome search analyses. CONCLUSIONS: Experience after four years of this five-year program (1995-2000) suggests that the newly initiated NHLBI Network Program mechanism is fulfilling many of the expectations for which it was designed. It may serve as a paradigm for future genetic research that can benefit from large sample sizes, frequent sharing of ideas among laboratories, and prompt independent confirmation of early findings, which are required in the search for common genes with relatively small effects such as those that predispose to human hypertension.

Adult↗

PubMed2000

The Family Risk Score for coronary heart disease: associations with lipids, lipoproteins, and body habitus in a middle-aged bi-racial cohort: The ARIC study.

PURPOSE: To examine the association between the Family Risk Score (FRS) for coronary heart disease (CHD) and body mass index (BMI), waist-to-hip ratio (WHR), high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein(a) protein [Lp(a)]. METHODS: FRS was computed from observed and expected CHD events using family data collected from 11467 black and white adults of the Atherosclerosis Risk in Communities Study (ARIC). BMI, WHR, and lipids adjusted for study center, race, education, BMI (except BMI), WHR (except for BMI and WHR), cigarette smoking, alcohol, and Keys' score were compared among low (FRS < -0.5), average (-0.5 to 0.5), and high (> 0.5) FRS using analysis of covariance. The association between FRS and these risk factors was compared to that for simpler estimates of family risk. RESULTS: Adjusted means of BMI, WHR, LDL, LP(a), and triglycerides were positively associated with FRS, whereas HDL cholesterol was inversely associated with FRS. Of demographic and behavioral factors, cigarette smoking was most strongly associated with FRS. Based on additional comparisons of adjusted means, high vs. low levels of FRS appear to correlate better with CHD risk factors than do the simpler family history assessments. CONCLUSIONS: In situations were genetic or clinical information is not available, FRS may be a favorable measure of familial burden for CHD.

Adult↗

PubMed2000

An economic evaluation of levofloxacin versus cefuroxime axetil in the outpatient treatment of adults with community-acquired pneumonia.

OBJECTIVE: To examine treatment costs of community-acquired pneumonia (CAP) in adult outpatients given oral (p.o.) levofloxacin or cefuroxime axetil as initial therapy. STUDY DESIGN: Patients with a primary diagnosis of CAP were enrolled in a multicenter, prospective, randomized, open-label, active-controlled Phase III clinical trial. Both inpatients and outpatients were assigned to 1 of 2 treatment groups: (1) intravenous (i.v.) or p.o. levofloxacin; or (2) i.v. ceftriaxone and/or p.o. cefuroxime axetil. METHODS: To make legitimate and meaningful cost comparisons between similar types of patients receiving drugs via the same route of administration (i.e., orally), this outpatient economic study examined the resource utilization of the 211 patients enrolled as outpatients who received oral formulations as initial treatment (levofloxacin, 103 patients; cefuroxime axetil, 108 patients). Resource utilization data and clinical trial data were collected concurrently. To generate cost estimates, Medicare cost estimates for resources were multiplied by the resource units used by patients in each treatment arm. RESULTS: Cost estimates indicated a total cost difference that favored the levofloxacin group (base case: $169; sensitivity analysis: $223 [P = .008]). The results for the base case were not significant (P = .094). In addition, within the cost categories, there was a statistically significant study drug cost differential favoring levofloxacin ($86; P = .0001 for both the base case and sensitivity analysis). CONCLUSION: Oral levofloxacin is less costly than oral cefuroxime axetil in the outpatient treatment of adults with CAP.

Adult↗

PubMed1999

Rods and cones project to the inner plexiform layer during development.

Mature rod and cone photoreceptor cells extend terminals to the outer plexiform layer (OPL), where they form characteristic spherules or pedicles, synapsing with the second-order neurons of the inner nuclear layer (INL). The present study demonstrates that, prior to the formation of this connectivity, immature rods and cones in the ferret extend processes beyond the level of the horizontal cells and future OPL, reaching the inner plexiform layer (IPL). The number of processes extending to the IPL increases steadily as the population of photoreceptor cells expands postnatally, reaching a maximum 2 weeks after birth. These processes are immunopositive for synaptophysin, and they terminate in two strata occupied by the dendrites of amacrine cells and ganglion cells. The frequency of these processes declines rapidly during the third postnatal week, and they are no longer detectable by the fourth postnatal week. Their loss is neither a consequence of photoreceptor cell death nor is it due to selective protein trafficking mechanisms that render them immunonegative. Rather, these processes retract to the level of the OPL during this period, coincident with the maturation of bipolar and horizontal cell processes. These results demonstrate that, despite the clear presence of environmental signals presaging the formation of the OPL, photoreceptor terminals initially ignore them to grow beyond this level of the retina. Rather, they detect and respond to signals within the IPL during this period, terminating in proximity to the processes of other cells in the inner retina, where they may contribute to transient retinal circuitry during early development.

Animals↗

PubMed1999

Effects of similarities in lifestyle habits on familial aggregation of high density lipoprotein and low density lipoprotein cholesterol: the NHLBI Family Heart Study.

It is generally assumed that familial aggregation of lipids relates to both genetic and shared environmental factors. To determine the degree to which familial similarities in lifestyle habits explain familial aggregation of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, the authors analyzed 1994-1996 data from 2,284 US adult participants in the National Heart, Lung, and Blood Institute Family Heart Study. For men and women, respectively, HDL cholesterol correlated with alcohol consumption (r = 0.27, p < 0.001; r = 0.21, p < 0.001), exercise (r = 0.06, p = 0.05; r = 0.10, p = 0.002), and smoking (r = -0.09, p = 0.005; r = -0.13, p < 0.001). There was strong familial aggregation of HDL cholesterol (parent-child, r = 0.32; sibling-sibling, r = 0.29), but less than 10% was explained by lifestyle habits. For LDL cholesterol, weak correlations were found for intake of total fat (r = 0.06, p = 0.07) and fruits/vegetables (r = -0.09, p = 0.005) among men and for smoking (r = 0.10, p = 0.002) among women. LDL cholesterol correlated strongly among family members (parent-child, r = 0.24; sibling-sibling, r = 0.31), but essentially none of this aggregation related to the lifestyle factors studied. This study suggests that lifestyle factors have little effect on the familial aggregation of HDL and LDL cholesterol.

Adult↗