Structural investigations of cross-linked hyaluronan.

Structural properties of several cross-linked hyaluronan derivatives, obtained by scanning electron microscopy, monodimensional NMR microscopy and small angle X-ray scattering of synchrotron radiation, are presented and compared with those observed for non-modified hyaluronic acid, used as a reference material. The experimental results, obtained in different media, showed a consistent picture of the synthesized matrices. In particular, the presence of zones of denser polymeric material observed by electron microscopy resulted in a higher transversal relaxation rate of the bulk water protons as well as in a decrease of the diffusion coefficient obtained by NMR microscopy. Moreover, the presence of polymer junction zones gave rise to the appearance of a well-defined correlation peak in the pattern of intensity of the scattered X-radiation.     

Epidemiology of Chronic Kidney Disease,With Special Emphasis on Chronic Kidney Disease of Uncertain Etiology,in the North Central Region of Sri Lanka

Background

The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka.

Methods

A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology.

Results

The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30–40 years; 7% in those aged 41–50 years, 20% in those aged 51–60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%.

Conclusions

Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.Key words: chronic kidney disease, uncertain etiology, epidemiology, North Central Province, male farmers, natural spring water     

What is the optimal approach for using a direct amplification test in the routine diagnosis of pulmonary tuberculosis? A preliminary assessment

OBJECTIVE: The aim of this study was to determine the most appropriate strategy for the rapid diagnosis of pulmonary tuberculosis (PTB) using a nucleic acid amplification (NAA) test. METHODOLOGY: This was a prospective study of 128 adult patients in whom respiratory secretions were tested for Mycobacterium tuberculosis by the AMPLICOR assay. The basis for starting PTB treatment was noted for each patient. The optimal approach was determined by using Bayes' theorem to compare different combinations of pretest probability, smear results with the AMPLICOR test. RESULTS: The incidence of PTB was 15.6%. In only one patient was treatment for PTB commenced because of a positive AMPLICOR result. The rest were managed according to the conventional approach which relied upon clinical judgment and direct smear. The optimal approach was to treat patients with high or intermediate pretest risk for PTB who returned positive AMPLICOR tests. The overall accuracies of the conventional approach, AMPLICOR test and optimal approach were 89.8, 95.3 and 96.1%, respectively. CONCLUSION: This small study suggests that NAA testing be limited to patients with high or intermediate pretest risk of PTB. In this group, positive results demand treatment while the management of those with negative results still relies on clinical judgment.     

ATPases and phosphate exchange activities in magnesium chelatase subunits of Rhodobacter sphaeroides

Three separate proteins, BchD, BchH, and BchI, together with ATP, insert magnesium into protoporphyrin IX. An analysis of ATP utilization by the subunits revealed the following: BchH catalyzed ATP hydrolysis at the rate of 0.9 nmol per min per mg of protein. BchI and BchD, tested individually, had no ATPase activity but, when combined, hydrolyzed ATP at the rate of 117.9 nmol/min per mg of protein. Magnesium ions were required for the ATPase activities of both BchH and BchI+D, and these activities were inhibited 50% by 2 mM o-phenanthroline. BchI additionally catalyzed a phosphate exchange reaction from ATP and ADP. We conclude that ATP hydrolysis by BchI+D is required for an activation step in the magnesium chelatase reaction, whereas ATPase activity of BchH and the phosphate exchange activity of BchI participate in subsequent reactions leading to the insertion of Mg²⁺ into protoporphyrin IX.     

Addition of ipratropium to nebulized albuterol in children with acute asthma presenting to a pediatric office

A prospective, randomized, double-blind study was conducted to determine whether there was any benefit to the addition of ipratropium to a single nebulized albuterol treatment in infants and children with mild to moderate acute asthma presenting to a pediatric office. There were no significant differences between the albuterol group and the combined albuterol-ipratropium group in the relief of the respiratory distress, disposition of the patients from the office, or in the incidence of relapse. The addition of ipratropium to nebulized albuterol is of no added benefit in the treatment of infants and children with mild-to-moderate acute asthma presenting to a pediatric office.     

Pattern of pesticide storage before pesticide self-poisoning in rural Sri Lanka

Background  

Deliberate self-poisoning with agricultural pesticides is the commonest means of suicide in rural Asia. It is mostly impulsive and facilitated by easy access to pesticides. The aim of this large observational study was to investigate the immediate source of pesticides used for self-harm to help inform suicide prevention strategies such as reducing domestic access to pesticides.     

High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study)

A total of 685 clinical Streptococcus pneumoniae isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs >/= 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC(90)s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC(90)s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan(19F) clone and the Spain(23F) clone could be one of the major reasons for the rapid increases in antimicrobial resistance among S. pneumoniae isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among S. pneumoniae isolates in many Asian countries, which are among the highest in the world published to date.     

A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a putative mediator of the cancer anorexia/weight loss syndrome. The current study was designed to determine whether etanercept (a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75-kilodalton TNF receptor linked to the Fc portion of human immunoglobulin [Ig] G1) could palliate this syndrome. METHODS: A total of 63 evaluable patients were randomly assigned to receive either etanercept at a dose of 25 mg subcutaneously twice weekly versus a comparably administered placebo. All patients had an incurable malignancy, acknowledged loss of weight and/or appetite as a concern, and reported a weight loss of >2.27 kg over 2 months and/or a daily intake of <20 calories/kg body weight. RESULTS: Over time, weight gain was found to be minimal in both treatment arms; no patient gained >or=10% of their baseline weight. Previously validated appetite questionnaires revealed negligible improvements in both treatment arms. The median survival was also comparable (175 days vs 148 days in etanercept-treated and placebo-exposed patients, respectively; P = .82). Finally, preliminary data regarding adverse events demonstrated that patients treated with etanercept had higher rates of neurotoxicity (29% vs 0%) but lower rates of anemia (0% vs 19%) and thrombocytopenia (0% vs 14%). Infection rates were negligible in both groups. Genotyping for TNF-alpha-238 and TNF-alpha-308 polymorphisms revealed no clinical significance for these genotypes, except for a preliminary association between presence of the -238 G/A genotype and relatively less favorable survival. CONCLUSIONS: Etanercept, as prescribed in the current trial, does not appear to palliate the cancer anorexia/weight loss syndrome in patients with advanced disease.     

Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3)

BACKGROUND: The antiepileptic agent, gabapentin, has been demonstrated to relieve symptoms of peripheral neuropathy due to various etiologies. On the basis of these data, a multicenter, double-blind, placebo-controlled, crossover, randomized trial was conducted to evaluate the effect of gabapentin on symptoms of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Patients with symptomatic CIPN who complained of 'average' daily pain scores of either 1) >/=4 on a 0-10 numerical rating scale (NRS); or 2) >/=1 on the 0-3 Eastern Cooperative Oncology Group neuropathy scale (ENS) were eligible (higher numbers indicate greater severity of symptoms in both scales). Patients were randomized to receive gabapentin (target dose, 2700 mg) or placebo for 6 weeks. Crossover occurred after a 2-week washout period. CIPN-related symptoms were evaluated weekly by questionnaires. Statistical methods followed established methods for crossover designs, including Student t tests to compare average intrapatient differences between treatments and linear models to adjust for potential concomitant covariates. RESULTS: There were 115 patients who were randomly assigned to the treatment or control arm. Both groups were well matched by symptoms at study entry. Changes in symptom severity were statistically similar between the 2 groups during the study. Adverse events were mild and similar in both groups. CONCLUSIONS: This trial failed to demonstrate any benefit to using gabapentin to treat symptoms caused by CIPN.