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[The effect of lovastatin in the treatment of primary hypercholesterolemia].

The effect of Lovastatin, an HMG. CoA reductase inhibitor, on serum lipids and apolipoproteins was studied in 40 cases of primary hypercholesterolemia in a 4-month period of treatment. The level of serum lipids did not change significantly after a 35-day period of placebo treatment as compared with that of the baseline (P greater than 0.5). The patients then took Lovastatin with the evening meal in a daily dose from 20 to 80 mg for 3 months. The results were as follows: Lovastatin reduced significantly the mean serum level of total cholesterol (TC) by 31.5% (P less than 0.001), LDL-C by 39.8% (P less than 0.001), Apo-B by 27.3% (P less than 0.002), and the ratio TC/HDL-C by 35.9% (P less than 0.01). It also reduced the mean serum level of triglycerides (TG) by 22.1% (P greater than 0.05) and increased that of HDL-C by 6.3% (P greater than 0.2) and Apo-AI by 1.6% (P greater than 0.5), but without much significance. The drug was well tolerated by all the patients. Transient elevation of CPK was noticed in 2 patients and AKP in one patient. 7 patients complained of gastrointestinal discomfort. All these side effects did not necessitate stop of the medication. We are, therefore, of the opinion that Lovastatin is an effective agent for lowering the serum level of TC, LDL-C and Apo-B.

Adult↗

High sensitivity and specificity of a laboratory-based serological test, pylori DTect ELISA, for detection of Helicobacter pylori infection.

A number of commercial ELISA kits are now available for detection of Helicobacter pylori infection. Generally, whereas the manufacturers have claimed high sensitivity and specificity, independent studies have often failed to confirm the results. The aim of this study was to independently evaluate the pylori DTect ELISA, a commercial kit for detection of H. pylori infection, in Australian patients with dyspepsia and reflux symptoms. Two hundred and nine consecutive patients (102 males and 107 females, mean age 52.8 years) who were referred for endoscopy due to upper gastrointestinal symptoms, but had not received anti-H. pylori therapy were enrolled. A 10 mL blood sample was obtained from each subject and used to evaluate the kit. The absorbance index (AI) was calculated from the mean of two readings of optical density (OD) of each serum sample. Eight biopsies from the gastric antrum (x3), body (x2), fundus (x2), and incisura (x1) were obtained from each patient for CLO-testing (x1), culture (x3), and histological examination (x4) for H. pylori. Overall, 84 (40.2%) patients were infected with H. pylori as determined by the biopsy-based "gold standard." The AIs ranged from 0 to 1.86; 0.12 to 1.86 in H. pylori positive patients and 0 to 1.49 in negative patients. The pylori DTect ELISA obtained an accuracy of 94 to 95% under AI ranges between 0.20 to 0.40, with the highest accuracy being 95% under AIs of 0.25 and 0.35. An AI of 0.25 was recommended as the best cut-off AI, with a sensitivity of 96.4%, specificity of 93.6%, positive predictive value of 91% and negative predictive value of 97.5%. It is concluded that the pylori DTect ELISA is accurate for detecting H. pylori infection in patients with dyspepsia and reflux symptoms in Australia, when an AI of 0.25 is taken as the cut-off value.

Adolescent↗

Use of asthma medication dispensing patterns to predict risk of adverse health outcomes: a study of Medicaid-insured children in managed care programs.

BACKGROUND: Regular use of inhaled anti-inflammatory (AI) medication improves outcomes for children with persistent asthma. OBJECTIVE: To relate 3 measures of asthma medication dispensing to physical health and hospital-based events among children with asthma who were enrolled in 1 of 5 managed care health plans. METHODS: Parents of Medicaid-insured children with asthma were interviewed at baseline and 1-year follow-up. Utilization data were collected from the health plans in which the children were enrolled. Subjects were stratified into 3 subgroups according to asthma severity: intermittent asthma; persistent asthma for which beta-agonist (BA) medication was dispensed infrequently (< or = 3 times per year); and persistent asthma for which BA medication was dispensed frequently (> or = 4 times per year). RESULTS: Baseline interviews were completed by 1,663 parents (63% response rate), 1,504 of whom were enrolled in their health plan for at least 11 months during the baseline year. Follow-up interviews were completed by 1,287 (86%) of the 1,504 parents. Among the subgroup of children with persistent asthma for whom BA was dispensed frequently, those who had 1 to 3 AI dispensings had a greater risk for hospital-based events than those with 6 or more AI dispensings. Baseline-year AI medication utilization patterns were not associated with follow-up-year outcomes. No clinically meaningful association was found in subgroups with less severe asthma; however, few AI medications were dispensed to these children. CONCLUSIONS: Policymakers and clinicians who wish to use medication-based measures to evaluate quality of asthma care should consider counting the number of times AI medication is dispensed among children with more severe asthma.

Administration, Inhalation↗

Targeting anti-apoptotic genes upregulated by androgen withdrawal using antisense oligonucleotides to enhance androgen- and chemo-sensitivity in prostate cancer.

The main obstacle to improved survival of advanced prostate cancer is our failure to prevent its progression to its lethal and untreatable stage of androgen independence. New therapeutic strategies designed to prevent androgen-independent (AI) progression must be developed before significant impact on survival can be achieved. Characterization of changes in gene expression profiles after androgen ablation and during progression to androgen-independence suggest that the various therapies used to kill neoplastic cells may precipitate changes in gene expression that lead to the resistant phenotype. Castration-induced increases in antiapoptosis genes, Bcl-2 and clusterin, help create a resistant phenotype, while antisense oligonucleotides can inhibit these adaptive cell survival mechanisms and enhance both hormone and chemotherapy. Ongoing efforts are necessary to identify additional molecular pathways mediating AI progression and chemoresistance, since complexities of tumor heterogeneity and adaptability dictate that optimal control over tumor progression will require multi-target systemic therapies.

Adenocarcinoma↗

Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00).

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of fulvestrant, an estrogen receptor antagonist, in postmenopausal women with hormone-responsive tumors progressing after aromatase inhibitor (AI) treatment. PATIENTS AND METHODS: This is a phase II, open, multicenter, noncomparative study. Two patient groups were prospectively considered: group A (n=70) with AI-responsive disease and group B (n=20) with AI-resistant disease. Fulvestrant 250 mg was administered as intramuscular injection every 28 (+/-3) days. RESULTS: All patients were pretreated with AI and 84% also with tamoxifen or toremifene; 67% had bone metastases and 45% liver metastases. Fulvestrant administration was well tolerated and yielded a clinical benefit (CB; defined as objective response or stable disease [SD] for >or=24 weeks) in 28% (90% confidence interval [CI] 19% to 39%) of patients in group A and 37% (90% CI 19% to 58%) of patients in group B. Median time to progression (TTP) was 3.6 (95% CI 3.0 to 4.8) months in group A and 3.4 (95% CI 2.5 to 6.7) months in group B. CONCLUSIONS: Overall, 30% of patients who had progressed following prior AI treatment gained CB with fulvestrant, thereby delaying indication to start chemotherapy. Prior response to an AI did not appear to be predictive for benefit with fulvestrant.

Adult↗

Effect of aluminum concentration on dental caries formation in the rat.

OBJECTIVE: Topically applied aluminum (AI) reduced fissure caries in rats with indigenous microflora, but neither therapeutic activity nor concentration effects have been studied in animals infected with caries-inducing bacteria. This study investigated the effects of solutions containing various AI concentrations on formation of smooth surface and sulcal caries in cariogenically challenged rats infected with Streptococcus sobrinus. METHODS: Weanling rats, inoculated with S. sobrinus, were randomly assigned to six groups which were topically treated twice daily with water (treatment control), a NaF solution of 100 parts/10(6) F (positive control), or AIK(SO4)2 solutions containing 100, 1000, 2000, or 4000 parts/10(6) AI. Rats were fed a high-sucrose diet and distilled water ad libitum for 10 weeks, then the molars were scored for enamel and dentin caries. RESULTS: Relative to the water control, NaF and all AI solutions significantly reduced prevalence of both smooth-surface and fissure caries. Protection by AI solutions was greater on smooth surfaces than sulcal areas. AI treatments reduced smooth surface scores by 49-71% and sulcal scores by 27-53%. For all comparisons the protective effect of the 100 parts/10(6) AI solution was less than solutions containing 1000 parts/10(6) AI or more. NaF and all AI solutions also significantly reduced the extent of lesions penetration into dentin. CONCLUSIONS: Topically applied AI reduced the formation and progression of both smooth surface and sulcal caries and showed evidence of a dose response in a rat model infected with S. sobrinus.

Administration, Topical↗

Prognostic factors in diffuse proliferative lupus nephritis.

BACKGROUND: Patients with diffuse proliferative lupus nephritis (DPLN) can have variable clinical course. Identification of the predictors of outcome would help to improve the management. We have studied the prognostic significance of clinical, laboratory and histological parameters in patients with DPLN. METHODS: Twenty nine patients diagnosed to be having DPLN seen between 1987 and 1991 were followed up for over 57 months. Parameters assessed for prognostic significance included serum creatinine, urine protein at the time of biopsy, blood pressure, type of immunosuppression, composite scores and individual components of activity index (AI) and chronicity index (CI). Kaplan-Meier survival curves were plotted and the results were compared using log rank test. Fishers' exact test was used to study the risk factors. RESULTS: End stage renal failure developed in 7/29 (24.1%) patients; 7/19 (36.8%) who had hypertension and 7/16 (43.8%) who had nephrotic proteinuria developed renal failure, while none who had normal blood pressure or nonnephrotic proteinuria, developed renal failure (p < 0.01). Three patients had high activity index (> 12) and all three developed renal failure. Other parameters such as age, gender, serum creatinine, type of immunosuppression, CI and individual components of AI failed to predict the outcome (p > 0.05). CONCLUSION: Hypertension, nephrotic proteinuria and high AI were predictive of progression to end stage renal failure in patients with diffuse proliferative lupus nephritis.

Adolescent↗

[Metabolic consequences of long-term antihypertensive treatment with co-dergocrine mesylate/nifedipine in high age groups].

Possible metabolic changes during chronic treatment is of specific importance for the development of antihypertensive drugs. The impact of a combination treatment with co-dergocrine mesilate/nifedipine (Pontuc; CAS 8067-24-1 resp. CAS 21829-25-4) on the lipid metabolism as well as hematological and biochemical values was evaluated in a group of hypertensive patients. HDL-cholesterol remained unchanged, whereas total cholesterol and LDL-cholesterol slightly decreased, apoprotein AI increased and apoprotein B decreased. In conclusion the results of this study indicate that co-dergocrine mesilate/nifedipine has no negative impact on the lipid metabolism in patients with essential hypertension.

Aged↗

Biosurfactants from Bacillus licheniformis: structural analysis and characterization.

The surface-active compounds of the strain Bacillus licheniformis were isolated and their structure was elucidated. The high surface-active capacity of the crude extract was basically due to traces of long-chain saturated fatty acids, especially of palmitic and stearic acids, to a mixture of small amounts of hydrocarbons with chain lengths of 20 and 22 carbons, and mainly to appreciable amounts of four slightly different lipopeptides. The lipopeptides were found to be a mixture of four closely related compounds. The lipophilic part consisting of i-, n-C14 or i-, ai-C15 beta-OH fatty acids was linked to the hydrophilic peptide moiety, which contained seven amino acids (Glu, Asp, Val, three Leu and Ile) by a lactone linkage. Fifteen milligrams per litre of the purified lipopeptide product decreased the surface tension of water from 72 mN m-1 to 27 mN m-1, characterizing the product as a powerful surface-active agent that compares favourably to other (bio)surfactants. Antibiotic activity was demonstrated against bacteria and yeasts.

Amino Acid Sequence↗

Quorum sensing and swarming migration in bacteria.

Bacterial cells can produce and sense signal molecules, allowing the whole population to initiate a concerted action once a critical concentration (corresponding to a particular population density) of the signal has been reached, a phenomenon known as quorum sensing. One of the possible quorum sensing-regulated phenotypes is swarming, a flagella-driven movement of differentiated swarmer cells (hyperflagellated, elongated, multinucleated) by which bacteria can spread as a biofilm over a surface. The glycolipid or lipopeptide biosurfactants thereby produced function as wetting agent by reducing the surface tension. Quorum sensing systems are almost always integrated into other regulatory circuits. This effectively expands the range of environmental signals that influence target gene expression beyond population density. In this review, we first discuss the regulation of AHL-mediated surface migration and the involvement of other low-molecular-mass signal molecules (such as the furanosyl borate diester AI-2) in biosurfactant production of different bacteria. In addition, population density-dependent regulation of swarmer cell differentiation is reviewed. Also, several examples of interspecies signalling are reported. Different signal molecules either produced by bacteria (such as other AHLs and diketopiperazines) or excreted by plants (such as furanones, plant signal mimics) might influence the quorum sensing-regulated swarming behaviour in bacteria different from the producer. On the other hand, specific bacteria can reduce the local available concentration of signal molecules produced by others. In the last part, the role and regulation of a surface-associated movement in biofilm formation is discussed. Here we also describe how quorum sensing may disperse existing biofilms and control the interaction between bacteria and higher organisms (such as the Rhizobium-bean symbiosis).

4-Butyrolactone↗

Antibiotic effects of WP-0405, a thermo-setting ofloxacin gel, on methicillin-resistant Staphylococcus aureus keratitis in rabbits.

PURPOSE: The chemotherapeutic effects and pharmacokinetics properties of WP-0405 (a thermo-setting in situ 0.3% ofloxacin-containing ophthalmic gel) and ofloxacin (a conventional 0.3% ofloxacin solution) on methicillin-resistant Staphylococcus aureus (MRSA) keratitis were compared in a rabbit model. METHOD: The single-instillation pharmacokinetics of WP-0405 and ofloxacin in the cornea, aqueous humor, conjunctiva, and iris-ciliary body were determined in normal rabbit eyes. To compare the duration of antimicrobial action, WP-0405 or ofloxacin was instilled oncedaily in an early-treatment model of keratitis, and corneas were either removed immediately or 4 or 8 h postinstillation. In another experiment, WP-0405 was instilled two or three times daily to compare its antibiotic efficacy with three-times daily instillation of ofloxacin in the same early-treatment model of keratitis; corneas were then removed after determining the extent of the abscess area. In another experiment, WP-0405 was instilled four or eight times daily to compare its effects with eight-times daily instillation of ofloxacin in a late-treatment model of keratitis, and corneas were removed. The number of viable bacteria in the corneas was determined in all experiments. RESULTS: Cmax and AUC0- in tissues treated with WP-0405 were 1.5-3.4-fold and 1.8-2.9-fold greater than those treated with ofloxacin, respectively. WP-0405 significantly reduced the number of viable bacteria for up to 8 h after a single instillation. WP-0405 not only significantly reduced the number of viable bacteria, but also the size of the abscess area at the same frequency of instillation. When compared to ofloxacin, WP-0405 exhibited an approximately equivalent antibiotic effect, with fewer administrations. CONCLUSIONS: As a result of its pharmacokinetics, WP-0405 had a more potent, longer-acting antibiotic effect than did ofloxacin. Furthermore, because of its lower required instillation frequency, which would improve patient compliance, WP-0405 has great potential therapeutic benefits.

Administration, Topical↗

Synthesis of autoinducer 2 by the lyme disease spirochete, Borrelia burgdorferi.

Defining the metabolic capabilities and regulatory mechanisms controlling gene expression is a valuable step in understanding the pathogenic properties of infectious agents such as Borrelia burgdorferi. The present studies demonstrated that B. burgdorferi encodes functional Pfs and LuxS enzymes for the breakdown of toxic products of methylation reactions. Consistent with those observations, B. burgdorferi was shown to synthesize the end product 4,5-dihydroxy-2,3-pentanedione (DPD) during laboratory cultivation. DPD undergoes spontaneous rearrangements to produce a class of pheromones collectively named autoinducer 2 (AI-2). Addition of in vitro-synthesized DPD to cultured B. burgdorferi resulted in differential expression of a distinct subset of proteins, including the outer surface lipoprotein VlsE. Although many bacteria can utilize the other LuxS product, homocysteine, for regeneration of methionine, B. burgdorferi was found to lack such ability. It is hypothesized that B. burgdorferi produces LuxS for the express purpose of synthesizing DPD and utilizes a form of that molecule as an AI-2 pheromone to control gene expression.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability.

This study assessed whether the improper use of pressurized metered-dose inhalers (pMDIs) is associated with decreased asthma control in asthmatics treated by inhaled corticosteroids (ICS). General practitioners (GPs) included consecutive asthmatic outpatients treated by pMDI-administered ICS and on-demand, short-acting beta2-agonists. They measured an asthma instability score (AIS) based on daytime and nocturnal symptoms, exercise-induced dyspnoea, beta2-agonist usage, emergency-care visits and global perception of asthma control within the preceding month; the inhalation technique of the patient also was assessed. GPs (n=915) included 4,078 adult asthmatics; 3,955 questionnaires were evaluable. pMDI was misused by 71% of patients, of which 47% was due to poor coordination. Asthma was less stable in pMDI misusers than in good users (AIS: 3.93 versus 2.86, p<0.001). Among misusers, asthma was less stable in poor coordinators (AIS: 4.38 versus 3.56 in good coordinators, p<0.001). To conclude, misuse of pressurized metered-dose inhalers, which is mainly due to poor coordination, is frequent and associated with poorer asthma control in inhaled corticosteroid-treated asthmatics. This study highlights the importance of evaluating inhalation technique and providing appropriate education in all patients, especially before increasing inhaled corticosteroid dosage or adding other agents. The use of devices which alleviate coordination problems should be reinforced in pressurized metered-dose inhaler misusers.

Administration, Inhalation↗

[Digestive salmonellosis in South Vietnam].

During the period January 1969 through October 1973, rectal swabs from 13,947 diarrhea patients of all ages at infectious disease hospital and children hospital in Saigon were examined. From these specimens 610 strains of Salmonella of all group were isolated. A total of 46 serologic types were encounted. The most commonly encounted were S. paratyphi B, S. java and S. typhimurium (group B). Most of Salmonella isolated were obtained from adult gastroenteritis. We have also studied the possible relation between human and animal salmonellosis. The rodents trapped from different aera in Saigon, fish and clams collected from different markets were examined by bacteriological surveys. From these specimens, 42 strains of Salmonella were isolated for a 2,2 percent isolation rate. Our study showed that Salmonella types which were isolated frequently from animal were encounted in man.

Adolescent↗

15N NMR spin relaxation dispersion study of the molecular crowding effects on protein folding under native conditions.

The effects of macromolecular crowding on protein stability and folding kinetics have been studied using the recently developed 15N spin relaxation dispersion technique. By applying this method to a redesigned apocytochrome b562, the kinetics and thermodynamics of the protein folding processes in both the presence and the absence of crowding agents have been characterized. The result indicates that, even under the mild crowded environments (in the presence of 85 mg/mL of PEG 20K), the folding rate of the protein can speed up significantly while the unfolded rate remains unchanged within experimental error.

Cytochrome b Group↗

Acquired ichthyosis associated with chronic graft-versus-host disease following allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia.

Acquired ichthyosis (AI) has rarely been described following bone marrow transplantation (BMT). We report a 29-year-old male, who underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) for chronic myelogenous leukemia, and who developed AI associated with chronic graft-versus-host disease (cGVHD). Both of these disorders were treated successfully with cyclosporin A. We conclude that AI may be related to an autoimmune process on the basis of cGVHD, and dermathopathologic evaluation must be performed in patients with skin changes suggesting AI following allogeneic bone marrow transplantation.

Adult↗

Phototoxicity of some bromine-substituted rhodamine dyes: synthesis, photophysical properties and application as photosensitizers.

The synthesis of some bromine-substituted rhodamine derivatives viz., 4,5-dibromorhodamine methyl ester (dye 2) and 4,5-dibromorhodamine n-butyl ester (dye 3) are reported. These dyes were synthesized to promote a more efficient cancer cell photosensitizer for potential use in in vitro bone marrow purging in preparation for autologous bone marrow transplantation. Spectroscopic and photophysical characterization of these dyes together with rhodamine 123 (dye 1) are reported in water, methanol, ethanol and also in a microheterogeneous system, sodium dodecyl sulfate. The possible mechanism of photosensitization is characterized in terms of singlet oxygen efficiency of these dyes. Singlet oxygen quantum yields for bromine-substituted dyes are in the range of 0.3-0.5 depending on the solvent. For dye 1 no singlet oxygen production is found. The photodynamic actions of these dyes in different cell lines are tested. It was found that dye 2 and dye 3 are efficient photosensitizers and mediate eradication of K562, EM2, myeloid cell lines (CML) and the SMF-AI rhabdomyosarcoma line.

Animals↗