Biomedical subjects

R R Williams

Publications and source records attributed to R R Williams.

241 records · Page 14Linked to original sources

PubMedDate not supplied

Aztreonam plus clindamycin versus tobramycin plus clindamycin in the treatment of intraabdominal infections.

In a multicenter, randomized clinical trial, aztreonam and tobramycin were compared for efficacy and safety in the treatment of intraabdominal infections. Patients were randomly assigned to one of the drug regimens, and all but two patients were treated concomitantly with clindamycin. Efficacy of treatment could not be evaluated for 107 of the 316 patients enrolled in the study. Among the 209 patients who could be evaluated (104 treated with aztreonam and 105 with tobramycin), microbiologic cure was achieved in 93% and 86%, respectively, and a favorable clinical response was noted in 85% of the patients in both groups. The frequency of adverse drug reactions in the two groups was similar. In this study, the efficacy and safety profiles of aztreonam plus clindamycin were comparable to those of tobramycin plus clindamycin.

Abdomen↗

PubMedDate not supplied

Efficacy of aztreonam in the treatment of skeletal infections due to Pseudomonas aeruginosa.

Twenty-eight patients with skeletal infections due to Pseudomonas aeruginosa were treated with aztreonam during two open, noncomparative, multicenter clinical trials. Ten patients with septic arthritis received 2 g of aztreonam three times a day (modal) for 30 days (mean). The mean follow-up period was 4 weeks. Microbiologic cure was achieved in all 10 patients; complete clinical cure, in eight; and partial clinical cure, in two. Eighteen cases of osteomyelitis were treated with 2 g of aztreonam three times a day (modal) for 40 days (mean), with a mean follow-up period of 6 months. Microbiologic cure was achieved in 17 patients. Relapse occurred 1 month after therapy in one patient. Complete clinical cure was achieved in 13 and partial clinical cure was achieved in five patients. The most common adverse reactions to aztreonam were a transient elevation in levels of hepatic enzymes and transient eosinophilia. Three superinfections and one subsequent infection occurred. These results support use of aztreonam for the treatment of skeletal infections due to P. aeruginosa.

Adolescent↗

PubMedDate not supplied

Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction.

In four large pedigrees with heterozygous familial hypercholesterolemia (FH) genetically linked to the low density lipoprotein receptor locus, we have observed a strong interaction between the presence of FH and a single apolipoprotein (apo) E2 allele, resulting in a markedly increased prevalence of type III dyslipoproteinemia (DLPIII). DLPIII was defined by chemical criteria. None of the patients with DLPIII had tuberous or palmar xanthomas characteristic of classically defined type III hyperlipoproteinemia. After exclusion of four persons with apo E 2-2 phenotype, there were 89 FH patients and 110 non-FH subjects. Definite DLPIII (defined as a very low density lipoprotein [VLDL] cholesterol to plasma triglyceride ratio greater than 0.30 with plasma triglycerides greater than or equal to 150 mg/dl) was present in 26% of 43 FH patients with a single E2 allele compared with only 3.4% of 29 non-FH subjects with an E2 allele (p = 0.003). To further characterize this interaction we performed a two-way analysis of covariance, after adjustment for age, sex, and body mass index, to test for any interaction between FH and the apo E loci. There was a statistically significant interaction between FH and the presence of a single E2 allele for the ratio of VLDL cholesterol to plasma triglycerides and for a newly derived estimate of beta-VLDL cholesterol concentration. Estimated beta-VLDL cholesterol level was strongly correlated with age in the subgroup with FH and an E2 allele but not in other subgroups. There was no difference in estimated beta-VLDL cholesterol between sexes. Correlation between estimated beta-VLDL cholesterol level and body mass index in persons older than 18 years was of only marginal significance and of similar magnitude in persons with or without an apo E2 allele. Present knowledge suggests that beta-VLDLs are highly atherogenic; if so, then a sizable subset of FH patients having at least one apo E2 allele and DLPIII may be at increased risk for premature coronary heart disease.

Adolescent↗

PubMedDate not supplied

Effects of three genetic loci in a pedigree with multiple lipoprotein phenotypes.

In the course of familial investigations of coronary artery disease, we identified an extended kinship in which several members were affected with type IIa hyperlipoproteinemia (HLPIIa), type III dyslipoproteinemia (DLPIII), or hypobetalipoproteinemia (HBLP). To study the genetic defects responsible for plasma lipoprotein abnormalities in this pedigree and to investigate the phenotypic effect of different genotypic combinations, we used molecular markers for apolipoprotein (apo) B, apo E, and the low density lipoprotein (LDL) receptor to characterize segregation at each locus. Linkage analysis showed that elevated LDL cholesterol levels and the HBLP phenotype were due to defects at the LDL receptor and the apo B loci, respectively. One pedigree member, who inherited both an LDL receptor allele linked with elevated LDL cholesterol levels and an apo B allele linked with HBLP, had a normal lipoprotein phenotype. Seven patients who simultaneously inherited the defective LDL receptor allele and one or two apo E2 alleles manifested DLPIII. The E2 alleles in this pedigree were shown by DNA sequence analysis to be the common E2 158 (arginine----cysteine) allele. These findings suggested a possible interaction between the abnormal LDL receptor and apo E2 alleles, resulting in the expression of DLPIII in the presence of a single copy of ago E2.

Adolescent↗

PubMedDate not supplied

Apolipoprotein, low density lipoprotein subfraction, and insulin associations with familial combined hyperlipidemia. Study of Utah patients with familial dyslipidemic hypertension.

Familial dyslipidemic hypertension (FDH) is a syndrome recently described from sibships selected for early familial hypertension and found to have one or more of three fasting lipid abnormalities [high triglycerides, low high density lipoprotein (HDL) cholesterol, high low density lipoprotein (LDL) cholesterol]. In further analyses of these same 131 hypertensive subjects, apolipoprotein A-I and B, fasting plasma insulin (adjusted for body mass index), and detailed anthropometrics were different in two subgroups of FDH. Of 63 FDH patients, 19 met the criteria for familial combined hyperlipidemia (FCHL); 44 did not, but still had high triglyceride and/or low HDL cholesterol levels. When compared to 20 normolipidemic hypertensive patients, the 19 hypertensive patients with FCHL had 196% higher very low density lipoprotein cholesterol (p = 0.0001), 33% higher apolipoprotein B (p = 0.0002), smaller LDL particles (p = 0.007), and 73% higher fasting insulin (p = 0.003), but no significant differences in body mass index or skinfold thicknesses. The other 44 FDH patients without FCHL had 33% lower HDL (p = 0.0001), with only 8% lower apolipoprotein A-I levels (p = 0.20); significantly higher subscapular skinfolds (p = 0.02), weights (p = 0.002), body mass index (p = 0.006), knee widths (p = 0.0007), and wrist circumferences (p = 0.0009); smaller, denser LDL subfractions (p = 0.001); and increased apolipoprotein B levels (p = 0.01) compared to the normolipidemic hypertensive group. Increased fasting insulin levels were similar to the normolipidemic group and significantly lower than the FCHL group after adjustment for body mass index, suggesting a relationship between obesity and fasting insulin levels only in the non-FCHL group. We conclude that FDH consists of at least two subgroups: 1) FCHL with high apolipoprotein B, small LDL particles, and increased fasting plasma insulin levels, and 2) a less well-defined residual having upper central obesity with low HDL cholesterol and high triglyceride levels. Elevated insulin levels found in both groups, but possibly originating through different physiological mechanisms, may provide the pathophysiological connections between dyslipidemia, obesity, and hypertension.

Apolipoprotein A-I↗

PubMedDate not supplied

Circulatory indirect calorimetry in the critically ill.

Circulatory indirect calorimetry (CIC) is a potentially useful method to assess the energy requirements of critically ill patients. Unlike respiratory indirect calorimetry (RIC), which measures oxygen utilization from inhaled and exhaled gases, CIC measures oxygen utilization from arterial and mixed venous blood. Twenty-two measurements in eight critically ill patients comparing RIC, CIC, and commonly used estimates of energy expenditure were performed. A significant correlation between RIC and CIC was identified (r = 0.831, p less than 0.001). Poor correlation was noted with either method and the commonly used estimates. CIC may be a useful tool in estimating energy expenditures in the critically ill.

Aged↗

PubMedDate not supplied

Three red cell sodium transport systems in hypertensive and normotensive Utah adults.

Sodium-lithium countertransport (SLC), sodium-potassium cotransport (CoT), and ouabain binding to sodium-potassium adenosine triphosphatase (Na, K-ATPase) sites were measured on fresh erythrocytes from hypertensive and normotensive Utah subjects with and without a first-degree relative with hypertension. SLC was measured as Li+ efflux into NaCl and MgCl2 media from Li+-loaded cells (5-7 mM). CoT was measured by monitoring Na+ and K+ efflux from cells loaded to 20-30 mM Na+ and 20-30 mMK+. Ouabain binding was determined for fresh cells using 3H-ouabain. Subjects were selected from pedigrees that showed a prevalence of hypertension. SLC was significantly elevated in 26.5% of the hypertensive subjects (p less than 0.001) as well as in 12.8% of the normotensives with a hypertensive first-degree relative (p less than 0.05). Although elevated SLC and decreased CoT have previously been associated with hypertension, no hypertensive subject in this study exhibited both abnormalities. All subjects with elevated SLC had normal CoT. A positive correlation between SLC and CoT was observed. Few hypertensive subjects (11.8%) had decreased CoT. In the majority of subjects studied, both SLC and CoT were normal: hypertensives 61.8%, normotensives with a hypertensive first-degree relative 61.7%, and other normotensives 58.7%. The number of ouabain-binding sites was not significantly altered among hypertensives, or their relatives, even though there was a positive correlation between SLC and the number of ouabain-binding sites.

Adult↗