Biomedical subjects

R B Johnson

Publications and source records attributed to R B Johnson.

At least 19 recordsLinked to original sources

PubMed2003

Sensitivity, specificity and accuracy of stress SPECT myocardial perfusion imaging for detection of coronary artery disease in the distribution of first-order branch vessels, using an anatomical matching of angiographic and perfusion data.

We sought to investigate the utility of stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the identification of coronary artery disease (CAD) in the distribution of first-order branch vessels. We evaluated 135 consecutive patients with coronary angiography and stress SPECT MPI. We anatomically matched angiography and SPECT to assess the sensitivity, specificity and accuracy of SPECT MPI for the detection of CAD in the distribution of first-order branches. Subgroup analysis for stress test performance and previous coronary artery bypass grafting (CABG) was also performed. The sensitivity, specificity and accuracy of stress SPECT MPI for the detection of CAD in the distribution of first-order branch vessels were all 67%. For isolated branch vessel CAD, stress SPECT MPI had a sensitivity of 44%. In patients without CABG, the sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order branch vessels were 71%, 67% and 68%, compared with 60%, 67% and 64% for patients with CABG. The sensitivity for isolated branch vessel CAD was 50% for patients without CABG, but only 29% for patients with CABG. The sensitivity and specificity for CAD in the distribution of branch vessels were similar for all patients for all stress test modalities and heart rate response (sensitivity, 64-69%; specificity, 61-69%). Stress SPECT MPI offers intermediate sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order coronary artery branch vessels. However, for isolated branch vessel CAD, stress SPECT has a lower sensitivity, particularly in patients with previous CABG.

Coronary Angiography↗

PubMed2002

Effect of estrogen deficiency on skeletal and alveolar bone density in sheep.

BACKGROUND: This study provides a longitudinal assessment of changes in alveolar and skeletal bone mineral density (BMD) in ovariectomized animals. METHODS: Following ovariectomy (OVX) (n = 6) or sham-operation (n = 6) intraoral radiographs were made at 4-month intervals and serum 17-beta-estradiol, osteocalcin, and interleukin (IL)-6, urinary deoxypyridinium, and salivary IL-6, deoxypyridinium, and osteocalcin concentrations were evaluated. Twelve months after surgery, animals were sacrificed and the mandible and radius/ulna removed. Bones were sectioned and radiographed. Mean BMD and cortical thicknesses were calculated from each region. RESULTS: OVX animals had a progressive decrease in serum 17-beta-estradiol, increased serum osteocalcin and IL-6, urinary deoxypyridinium and salivary IL-6, osteocalcin and deoxypyridinium (P < 0.001), suggesting that they were becoming osteoporotic. The BMD of the radius/ulna and mandibular alveolar bone was significantly reduced in OVX animals (P < 0.05 and P < 0.001, respectively). Reduced alveolar bone BMD became evident in OVX animals 6 months after surgery and became more severe during the subsequent 6 months. Alveolar crestal height was also significantly reduced in OVX animals (P < 0.001). These biochemical and density changes preceded a significant reduction in serum 17-beta-estradiol, which occurred between 4 and 8 months following surgery. CONCLUSIONS: Serial measurements of alveolar BMD predicts loss of skeletal BMD in OVX sheep. Changes in alveolar BMD precede estrogen deficiency, suggesting that early signs of reduced BMD may be detected in peri-menopausal women. The presence of biomarkers of bone metabolism within saliva and their correlation with reduced BMD suggests that saliva could be used as an adjunct screening method for assessment of skeletal bone density.

Alveolar Process↗

PubMed2001

Activation of human rhinovirus-14 3C protease.

The catalytic efficiency of human rhinovirus-14 (HRV14) 3C protease as a function of solvents and other regulators has been investigated using synthetic peptides as substrates. The proteolytic activity of HRV14 3C was found to be strongly stimulated by a series of anions in vitro and the activation was accompanied by changed Km, kcat, and increased kcat/Km values. A more than 72-fold increase in the 3C catalytic efficiency toward peptide substrates was observed in the presence of 0.8 M sodium sulfate. Several approaches, including size-exclusion chromatography and chemical cross-linking experiments, suggested that no oligomerization of the 3C enzyme occurred in the presence of activating anions. However, the anions did induce a significant conformational change of HRV14 3C protease, as revealed by circular dichroism spectrometry and tyrosine fluorescence analyses, which might contribute to 3C enzyme activation. Finally, the results obtained from 3C protease inhibitor studies suggested that the S1 specificity pocket of HRV14 3C was mainly affected by the activating anions. An induced-fit catalysis mechanism for viral proteases is discussed.

3C Viral Proteases↗

PubMed2001

Validation of a model of left ventricular segmentation for interpretation of SPET myocardial perfusion images.

Several models of left ventricular segmentation have been developed that assume a standard coronary artery distribution, and are currently used for interpretation of single-photon emission tomography (SPET) myocardial perfusion imaging. This approach has the potential for incorrect assignment of myocardial segments to vascular territories, possibly over- or underestimating the number of vessels with significant coronary artery disease (CAD). We therefore sought to validate a 17-segment model of myocardial perfusion by comparing the predefined coronary territory assignment with the actual angiographically derived coronary distribution. We examined 135 patients who underwent both coronary angiography and stress SPET imaging within 30 days. Individualized coronary distribution was determined by review of the coronary angiograms and used to identify the coronary artery supplying each of the 17 myocardial segments of the model. The actual coronary distribution was used to assess the accuracy of the assumed coronary distribution of the model. The sensitivities and specificities of stress SPET for detection of CAD in individual coronary arteries and the classification regarding perceived number of diseased coronary arteries were also compared between the two coronary distributions (actual and assumed). The assumed coronary distribution corresponded to the actual coronary anatomy in all but one segment (#3). The majority of patients (80%) had 14 or more concordant segments. Sensitivities and specificities of stress SPET for detection of CAD in the coronary territories were similar, with the exception of the RCA territory, for which specificity for detection of CAD was better for the angiographically derived coronary artery distribution than for the model. There was 95% agreement between assumed and angiographically derived coronary distributions in classification to single- versus multi-vessel CAD. Reassignment of a single segment (segment #3) from the LCX to the LAD territory further improved the model's fit with the anatomic data. It is concluded that left ventricular segmentation using a model with assumed coronary artery distribution is valid for interpretation of SPET myocardial perfusion imaging.

Coronary Angiography↗

PubMed2001

Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia.

OBJECTIVES: We sought to optimize vascular endothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens. BACKGROUND: Although VEGF165 is one of the most potent pro-angiogenic growth factors, VEGF165 treatment for myocardial ischemia has been hampered by low efficacy and dose-limiting hypotension after systemic or intracoronary delivery. METHODS: This study evaluated the effect of intravenous or intracoronary rhVEGF165 in the presence or absence of nitric oxide (NO) synthase inhibition in a porcine model of chronic myocardial ischemia. Forty-two Yorkshire pigs with chronically occluded left circumflex coronary arteries were randomly assigned to receive 10 microg/kg of VEGF165: 1) rapid (40 min) intravenous VEGF165 0.25 microg/kg/min, 2) slow (200 min) intravenous VEGF165 0.05 microg/kg/min, 3) rapid intracoronary VEGF165 0.25 microg/kg/min, 4) rapid intracoronary VEGF165 0.25 microg/kg/min + nitro-L-arginine methyl ester hydrochloride (L-NAME) or 5) rapid vehicle infusion. RESULTS: Intracoronary and intravenous VEGF165 induced hypotension. Intracoronary VEGF-induced hypotension was blocked by L-NAME. Coronary angiography three weeks after treatment showed improvement in collateral index in both intracoronary groups but not the intravenous VEGF165 groups. Likewise, myocardial blood flow and microvascular function in the ischemic territory improved in both intracoronary groups but not in the intravenous groups. Global and regional myocardial function showed no significant improvements in any groups. CONCLUSIONS: Intracoronary infusion of VEGF165 significantly improves blood flow to the ischemic myocardium. Concomitant administration of L-NAME inhibits VEGF-induced hypotension while most likely preserving VEGF-induced angiogenesis. Intravenous infusion of VEGF165 was not effective in augmenting either myocardial flow or function in this model.

Animals↗

PubMed2001

In vitro effects of azithromycin on Salmonella typhi: early inhibition by concentrations less than the MIC and reduction of MIC by alkaline pH and small inocula.

To explain good clinical results of azithromycin in patients with typhoid fever, 10 strains of Salmonella typhi were grown in cation-adjusted Mueller-Hinton broth. MICs of azithromycin were 4-16 mg/L. At a sub-MIC of 2 mg/L, early inhibition of growth was shown at 2, 4 and 8 h of incubation, but at 24 and 48 h growth to turbidity occurred. At 4 mg/L, inhibition occurred up to 8 h, after which growth towards turbidity followed. Elongated curved bacilli formed in broth containing 4 mg/L after 24-48 h. Adjusting the pH of the broth with phosphate-citrate buffer to 7.5 and 8.0 caused reductions in MICs to 0.25-0.5 mg/L. Large inocula of 10(6) cfu/mL resulted in median MICs four- to six-fold greater than with inocula of 10(1)-10(3) cfu/mL. An inoculum of 10 bacteria per mL in broth at pH 7.5 resulted in an MIC of 0.13 mg/L. Clinical benefits in patients may occur because of early inhibition by sub-MIC concentrations of azithromycin, and due to lower MICs at alkaline pH and lower MICs with small inocula that may correspond to the low-grade bacteraemia in typhoid fever.

Anti-Bacterial Agents↗

PubMed2001

Survival of rotavirus antibody activity derived from bovine colostrum after passage through the human gastrointestinal tract.

BACKGROUND: Rotavirus is a major cause of infectious diarrhea in infants and young children. Several studies have shown that hyperimmune bovine colostrum, derived from cows immunized with rotavirus, can prevent rotavirus diarrhea when given passively. The objective of this study was to determine whether colostral antibody activity survived transit through the gut by measuring the level of rotavirus antibody activity in the feces. METHODS: Hyperimmune colostrum containing different levels of rotavirus antibody was administered to 105 children attending nine Adelaide childcare centres. Subjects were asked to drink 100 ml of whole milk supplemented with colostrum 3 times a day, for a period of 6 days. Stool samples were collected from the subjects before, during, and after consumption of the study product. Rotavirus activity was determined using a novel virus reduction enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay. RESULTS: Rotavirus antibody activity was detected in 521 (86%) of 602 fecal specimens obtained during the study using the virus reduction ELISA. The antibody activity was detected as early as 8 hours after ingestion of hyperimmune colostrum and up to 72 hours after consumption had ceased. There was a strong relation (r = 0.81) between the titer of rotavirus antibody administered to subjects and the level of antibody activity detected in the feces. CONCLUSIONS: The results show that antirotavirus activity survived passage through the gut. Therefore, passive immunotherapy may be used to prevent or treat infectious diseases that affect the entire length of the gastrointestinal tract.

Antibodies, Viral↗

PubMed2001

Identification and characterization of a monofunctional glycosyltransferase from Staphylococcus aureus.

A gene (mgt) encoding a monofunctional glycosyltransferase (MGT) from Staphylococcus aureus has been identified. This first reported gram-positive MGT shared significant homology with several MGTs from gram-negative bacteria and the N-terminal glycosyltransferase domain of class A high-molecular-mass penicillin-binding proteins from different species. S. aureus MGT contained an N-terminal hydrophobic domain perhaps involved with membrane association. It was expressed in Escherichia coli cells as a truncated protein lacking the hydrophobic domain and purified to homogeneity. Analysis by circular dichroism revealed that secondary structural elements of purified truncated S. aureus MGT were consistent with predicted structural elements, indicating that the protein might exhibit the expected folding. In addition, purified S. aureus MGT catalyzed incorporation of UDP-N-acetylglucosamine into peptidoglycan, proving that it was enzymatically active. MGT activity was inhibited by moenomycin A, and the reaction product was sensitive to lysozyme treatment. Moreover, a protein matching the calculated molecular weight of S. aureus MGT was identified from an S. aureus cell lysate using antibodies developed against purified MGT. Taken together, our results suggest that this enzyme is natively present in S. aureus cells and that it may play a role in bacterial cell wall biosynthesis.

Bacterial Proteins↗

PubMed2001

Biochemical characterization of signal peptidase I from gram-positive Streptococcus pneumoniae.

Bacterial signal peptidase I is responsible for proteolytic processing of the precursors of secreted proteins. The enzymes from gram-negative and -positive bacteria are different in structure and specificity. In this study, we have cloned, expressed, and purified the signal peptidase I of gram-positive Streptococcus pneumoniae. The precursor of streptokinase, an extracellular protein produced in pathogenic streptococci, was identified as a substrate of S. pneumoniae signal peptidase I. Phospholipids were found to stimulate the enzymatic activity. Mutagenetic analysis demonstrated that residues serine 38 and lysine 76 of S. pneumoniae signal peptidase I are critical for enzyme activity and involved in the active site to form a serine-lysine catalytic dyad, which is similar to LexA-like proteases and Escherichia coli signal peptidase I. Similar to LexA-like proteases, S. pneumoniae signal peptidase I catalyzes an intermolecular self-cleavage in vitro, and an internal cleavage site has been identified between glycine 36 and histidine 37. Sequence analysis revealed that the signal peptidase I and LexA-like proteases show sequence homology around the active sites and some common properties around the self-cleavage sites. All these data suggest that signal peptidase I and LexA-like proteases are closely related and belong to a novel class of serine proteases.

Amino Acid Sequence↗

PubMed2001

Leptin within healthy and diseased human gingiva.

BACKGROUND: Plasma leptin concentrations are reported to be elevated in patients with inflammatory diseases. There is no consensus concerning the biological mechanism for this phenomenon. To date, tissue leptin concentrations have not been assessed within normal or inflamed gingiva. The purpose of this study was to assess concentrations of human leptin within healthy and diseased gingiva to define its possible role in periodontal disease progression. METHODS: Healthy (non-hemorrhagic gingiva adjacent to a < or =3 mm gingival sulcus) and inflamed gingiva (hemorrhagic gingiva adjacent to a > or =3 mm periodontal pocket) were studied. Leptin, vascular endothelial growth factor (VEGF; to assess potential vascular expansion), and interleukin-6 (IL-6; to assess periodontal disease activity and severity) concentrations were assessed within solubilized gingival biopsies by enzyme-linked immunosorbent assay. Data were grouped by sulcular depth and compared by factorial analysis of variance, regression analysis, and Scheffé comparisons. RESULTS: Leptin concentrations were highest within gingiva adjacent to a < or =3 mm sulcus and progressively declined within gingiva adjacent to a > or =3 mm sulcus. VEGF concentrations were highest within gingiva adjacent to 4 to 6 mm pockets and nearly equivalent in healthy (< or =3 mm sulcus) and severely diseased gingiva (>6 mm sulcus). IL-6 was positively correlated and leptin negatively correlated with adjacent probing depth; IL-6 concentration was significantly higher and leptin significantly lower in gingiva adjacent to >6 mm pockets compared to sites adjacent to <6 mm pockets (P<0.001). CONCLUSIONS: Human leptin is present within healthy and marginally inflamed gingiva and decreases in concentration as the adjacent probing depth increases. When leptin concentrations decreased (> or =3 mm sulcus), VEGF concentrations increased, suggesting that leptin could be released from gingiva coincident to vascular expansion. Thus, gingiva, in addition to adipose tissue, could be a source of circulating leptin in patients with periodontal disease. This possibility requires further investigation.

Adolescent↗

PubMed2000

Specificity and mechanism analysis of hepatitis C virus RNA-dependent RNA polymerase.

The RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene has been expressed as a nonfusion protein in bacterial cells and purified to homogeneity using sequential chromatographic columns. The purified NS5B protein exhibited RNA-dependent RNA polymerase activity using poly(A) template and the K(m) and V(max) were determined as 8.4 microM and 1976 pmol/mg-min, respectively. This full-length NS5B protein exhibited much stronger binding affinity toward the 30-mer poly(G) than other homopolymeric RNAs of the same size. For the first time, we demonstrate that the HCV NS5B was able to bind various ribonucleotides. Using a panel of oligonucleotides varying in length, we studied the NS5B catalytic efficiency and proposed the size of the NS5B active site to be 8-10 nucleotides. The multifunctional nature of NS5B protein is also discussed and compared with other viral RNA polymerases.

Binding Sites↗

PubMed2000

De novo RNA synthesis catalyzed by HCV RNA-dependent RNA polymerase.

The 65 kDa RNA-dependent RNA polymerase (NS5B), encoded by the hepatitis C virus (HCV) genome, is a key component involved in viral replication. Here we provide the direct evidence that purified HCV polymerase catalyzed de novo RNA synthesis in a primer-independent manner using homopolymers and HCV RNA as templates. The enzyme could utilize both polyC and polyU as templates for de novo RNA synthesis, suggesting that NS5B specifically recognized pyrimidine bases for initiation. More importantly, NS5B also catalyzed de novo RNA synthesis with an HCV RNA template; the resulting nascent RNA products, smaller than the template used, contained ATP as the first nucleotide. These results indicate that the newly synthesized RNAs did not result from template self-priming and suggest that a replication initiation site in the HCV RNA genome is a uridylate.

3' Untranslated Regions↗

PubMed2000

Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and interleukin-1-beta in vitro.

Gingival overgrowth commonly occurs coincident to therapy with calcium channel blockers. The biologic mechanism for this condition is unknown; however, many clinicians suggest that poor oral hygiene may contribute to development of the overgrowth. This study tests the hypothesis that collagenous protein synthesis by gingival fibroblasts is synergistically enhanced when they are exposed to both nifedipine (N) and the pro-inflammatory cytokine, interleukin-1-beta, a cytokine expressed in inflamed gingiva. Human gingival fibroblasts were isolated from biopsies of normal gingiva and cells separated into two groups. Group 1 was exposed to media containing 0, 5, 50, or 500 pg/ml IL-1-beta, or 10(-7) M N for 7 days; Group 2 was exposed to those concentrations of IL-1-beta +10(-7) M N. [3H]-proline was added to the medium for the final 24 h. Cells and matrix were harvested and radioactivity determined by liquid scintillation analysis. Means (d.p.m./10(3) cells) were compared by factorial ANOVA and Scheffé comparisons. Collagenous protein synthesis was significantly reduced by 5 pg/ml IL-1-beta +10(-7) M N and enhanced by 500 pg/ml IL-1-beta +10(-7) M N as compared to N or IL-1-beta alone. Thus, patients may be more susceptible to gingival overgrowth coincident to nifedipine therapy as a result of the synergistic enhancement of connective tissue synthesis by these agents.

Analysis of Variance↗

PubMed1999

Identification and characterization of human rhinovirus-14 3C protease deamidation isoform.

A purified recombinant human rhinovirus-14 3C protease preparation contained only approximately 50% active enzyme as titrated using specifically designed irreversible 3C protease inhibitors. Analysis of the purified 3C protein by isoelectric focusing showed differently charged 3C isoforms that had isoelectric points (pI) of 8.3 (55%) and 9.0 (45%), with the latter one being consistent with the predicted pI of the human rhinovirus-14 3C protein. Further analysis indicated that the pI 8.3 protein was the deamidated form of 3C, and it displayed approximately 10-fold reduced cleavage activity relative to the original 3C protease sample. Peptide mapping followed by sequence analysis revealed that a single asparagine, Asn-164, was deamidated to aspartic acid in the pI 8.3 isoform. Converting Asn-164 to Asp by site-directed mutagenesis resulted in a mutated 3C protease with extremely low activity, as seen with the pI 8.3 isoform, indicating a role of Asn-164 in substrate recognition and binding. In addition, the deamidated 3C protease was found to be present in vivo, and its abundance was related to the viral replication cycle. Moreover, mutant virus carrying Asp-164 showed reduced viability in infected cells. Taken together, our data suggest that 3C protein deamidation plays a role in the regulation of its enzymatic activity.

3C Viral Proteases↗

PubMed1999

The effectiveness of two sterilization methods when different precleaning techniques are employed.

The effectiveness was investigated of methods for the preparation of dental handpieces prior to sterilization procedures utilizing ethylene oxide (ETO) gas. The handpieces were cleaned using either a forced-air purging unit (group 1) or by flushing with air and water from the dental unit (group 2). They were inoculated with either Bacillus subtilis or Streptococcus mutans. After exposure to either steam or ETO gas, the handpieces were flushed with saline and the viability of recovered bacteria assessed. No viable bacteria were recovered from group 1 handpieces treated with either ETO gas or steam. However, viable S. mutans were recovered from group 2 handpieces following exposure to ETO gas. Thus, the use of a high-pressure forced-air purging unit may be required for the reliable sterilization of dental handpieces by ETO gas, as viable S. mutans could be recovered from untreated handpieces exposed to ETO gas.

Air Pressure↗

PubMed1999

Three-dimensional echocardiography improves accuracy and compensates for sonographer inexperience in assessment of left ventricular ejection fraction.

This study was performed to determine whether 3-dimensional echocardiography (3DE) with a magnetic tracking system for image plane localization, which unlike standard 2-dimensional echocardiography (2DE), does not require acquisition of specific image planes or "standard views" for quantitative measurement of left ventricular volume and ejection fraction (EF), could compensate for sonographer inexperience. Eight adults underwent magnetic resonance imaging (MRI) scanning; they also had 2DE and 3DE performed by 2 experienced and 3 novice sonographers. Data were analyzed by a single expert reader blinded to patient and sonographer identity. Linear regression of MRI EF (reference standard) against echocardiographic EF yielded the following results, where RD indicates the residual difference between measured MRI values and those predicted using echocardiographic results: expert 3DE: r = 0.97, RD = 2.4%, and r = 0.96, RD = 2.8%; novice 3DE: r = 0. 83, RD = 5.1%, to r = 0.95, RD = 4.8%; expert 2DE: r = 0.85, RD = 4. 8%, and r = 0.86, RD = 4.9%; and novice 2DE: r = 0.34, RD = 11.7%, to r = 0.69, RD = 6.6%. Comparison of error variances indicated that novices who used 3DE equaled the performance of experts who used 2DE, although experts were always more accurate than novices when both used the same echocardiographic method (3DE vs 3DE, 2DE vs 2DE). In a comparison of methods, 3DE was always superior to 2DE, regardless of sonographer experience. Three-dimensional echocardiography allows even novice sonographers to obtain diagnostic-quality data sets, which they were unable to accomplish with 2DE. These results suggest that scanning with 3DE, combined with remote expert interpretation, may be useful in providing echocardiographic services in regions where they are presently unavailable.

Adult↗

PubMed1999

Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate.

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four-hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (+/-SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: -11.9/-7.4 +/- 0.6/0.5 v -11.6/-6.5 +/- 0.6/0.5 mm Hg) and heart rate (1.0/1.7 +/- 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: -12.6/-8.1 +/- 0.7/0.4 v -11.3/-6.4 +/- 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 +/- 0.4 v 0.4 +/- 0.4 beats/min; P < .001; early morning, 3.5 +/- 0.7 v 0.5 +/- 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.

Antihypertensive Agents↗

PubMed1999

Treatment of typhoid fever with azithromycin versus chloramphenicol in a randomized multicentre trial in India.

To compare the clinical and bacteriological efficacies of azithromycin and chloramphenicol for treatment of typhoid fever, 77 bacteriologically evaluable adults, with blood cultures positive for Salmonella typhi or Salmonella paratyphi A susceptible to their assigned drugs, were entered into a randomized open trial at four hospitals in India. Forty-two patients were randomized to receive azithromycin 500 mg p.o. od for 7 days and 35 to receive chloramphenicol 2-3 g p.o. od in four divided doses for 14 days. Thirty-seven patients (88%) in the azithromycin group responded with clinical cure or improvement within 8 days and 30 patients (86%) in the chloramphenicol group responded with cure or improvement. By day 14 after the start of treatment, all patients treated with azithromycin and all except two of the patients treated with chloramphenicol (94%) were cured or improved. Blood cultures repeated on day 8 after start of therapy showed eradication of organisms in 100% of patients in the azithromycin group and 94% of patients in the chloramphenicol group. By day 14 the eradication rate in the chloramphenicol group had increased to 97%. Stool cultures on days 21 and 35 after start of treatment showed no prolonged faecal carriage of Salmonella spp. in either group. These results indicate that azithromycin given once daily for 7 days was effective therapy for typhoid fever in a region endemic with chloramphenicol-resistant S. typhi infection and was equivalent in effectiveness to chloramphenicol given to patients with chloramphenicol-susceptible infections.

Adolescent↗