Bactericidal activity of moxifloxacin against multidrug-resistant Streptoccocus pneumoniae at clinically achievable serum and epithelial lining fluid concentrations compared with three other antimicrobials

Time-kill studies compared the activities of moxifloxacin with those of levofloxacin, azithromycin and amoxicillin-clavulanate against 10 pneumococcal strains with various drug susceptibilities. Three Streptococcus pneumoniae strains were resistant to moxifloxacin: 6, 7 and 2 strains were resistant to levofloxacin, azithromycin and amoxicillin-clavulanate, respectively. Of these, 1 strain was resistant to all antimicrobial agents studied. Moxifloxacin and amoxicillin-clavulanate were bactericidal after 24h at serum Cmax levels against 9 and 8 strains, respectively, while levofloxacin and azithromycin were bactericidal against 3 and 2 strains, respectively. A higher activity was only observed for amoxicillin-clavulanate for logarithmic phase cultures at 1, 4 and 8h compared with stationary phase organisms. Amoxicillin-clavulanate and moxifloxacin were bactericidal at free serum levels (protein unbound) after 24h against 8 and 3 strains, respectively. Moxifloxacin was bactericidal at epithelial lining fluid levels against all strains at 24h, including one moxifloxacin, amoxicillin-clavulanate and azithromycin-resistant strain; lower levels of bactericidal activity was observed for levofloxacin, azithromycin and amoxicillin-clavulanate against 7, 2 and 4 strains, respectively. This demonstrated the importance of moxifloxacin tissue levels.     

Penile arteries and erection

Alterations in the flow of blood to and from the penis are thought to be the most frequent causes of male erectile dysfunction and, therefore, the present review focuses on the penile vasculature. In the flaccid state, tonic noradrenaline release from the sympathetic nerves contracts penile arterial and corporal smooth muscle through activation of postjunctional alpha(1)-adrenoceptors, both by increasing intracellular calcium and by enhancing the sensitivity of the contractile apparatus for calcium. In addition, noradrenaline inhibits vasodilatatory neurotransmitter release by prejunctional alpha(2)-adrenoceptors. The exact role of the sympathetic neurotransmitters, neuropeptide Y and adenosine 5'-triphosphate, in erection is largely unknown. Penile vasodilatation during erection is mediated by nitric oxide (NO) through activation of guanylyl cyclase in the smooth muscle layer, followed by increases in cyclic guanosine monophosphate lowering of intracellular calcium and desensitisation of the contractile apparatus for calcium. Acetylcholine, vasoactive intestinal peptide as well as peptides in sensory nerves probably also play a role in penile vasodilation. Increased flow through the penile arteries stimulates the endothelium leading to release of NO, prostanoids and a non-NO non-prostanoid factor, and as such enhances the vasodilatation, while the role of endothelium-derived contractile factors in penile vasoconstriction is not clear. Erectile dysfunction shares arterial risk factors with ischaemic heart disease, and diabetes, age, and hypercholesterolaemia are associated with impairment of both neurogenic and endothelium-dependent vasodilator mechanisms in corpus cavernosum. Only few studies have investigated the impact of these risk factors on the penile vasculature, although recent evidence suggests that arterial insufficiency precedes changes in corpus cavernosum leading to erectile dysfunction.     

Clinical and laboratory aspects of acute bacterial meningitis in infants

OBJECTIVE: to describe clinical and laboratorial characteristics of acute bacterial meningitis in infants. METHOD: data from the prospective follow-up of infants with acute bacterial meningitis, admitted at the Hospital Couto Maia between March and December 1997, were analyzed with specific statistical software. RESULTS: acute bacterial meningitis was more prevalent in infants with ages varying from 6 months to 1 year. The most frequent etiologic agent was Haemophilus influenzae. The global lethality was 25.9% and among the survivors 39.3% left the hospital with some abnormality in the neurological exam compatible with the brain involvement. CONCLUSION: acute bacterial meningitis in infants is a high lethality disease that in the majority of cases can be prevented. We consider of great relevance the adoption of health prevention strategies in order to reduce the incidence of this disease.     

Effect of salmeterol on seasonal changes in airway responsiveness and exhaled nitric oxide in pollen-sensitive asthmatic subjects

OBJECTIVE: Using a model of natural allergen exposure, we examined the effect of regular treatment with salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO). DESIGN: Double-blind, randomized, parallel-group study. SETTING: Specialist allergy unit in a university hospital. PATIENTS: Asthmatic patients sensitized to pollen allergens were randomly allocated to monotherapy with salmeterol (n = 14) or placebo (n = 13). INTERVENTIONS: Salmeterol, 25 micro g, and placebo inhalers, two puffs bid, for 6 weeks. MEASUREMENTS: Spirometry, the level of a provocative concentration of a substance (methacholine) causing a 20% fall in FEV(1) (PC(20)), the PC(20) level for adenosine 5'-monophosphate (AMP), and ENO were measured before the pollen season and were repeated at the height of the pollen season after 6 weeks of treatment with salmeterol or placebo. RESULTS: The decrease in FEV(1) during the pollen season was significantly larger in the placebo group than in the salmeterol group, the mean difference in the change between the groups being 0.20 L (95% confidence interval, 0.03 to 0.35; p = 0.047). Changes in PC(20) for methacholine, PC(20) for AMP, and ENO levels were not significantly different between treatment groups. However, a mean (+/- SEM) decrease in the PC(20) for methacholine of -1.0 +/- 0.4 doubling concentrations was observed within the placebo group (p = 0.03), whereas no significant changes were observed within the salmeterol group. A significant decrease in PC(20) for AMP (doubling concentrations) was observed within the placebo group (-2.1 +/- 0.6; p = 0.003) and the salmeterol group (-1.5 +/- 0.4; p = 0.003). ENO concentrations increased significantly among the placebo and the salmeterol groups during natural pollen exposure. CONCLUSION: These observations indicate that natural allergen exposure and the regular use of salmeterol are not associated with a greater increase in ENO and airway responsiveness than allergen exposure alone.     

Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?

To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly. Fifteen dermatopathologists examined the cases separately. Margin status was categorized as positive, negative, or indeterminate. Kappa statistics were calculated per dermatopathologist and per case. One case from each group was excluded because epidermis was not available in the routine sections. Of 330 evaluations (22 cases, 15 dermatopathologists), there were 132 diagnostic discrepancies (40.0%): 66 each for MM and NML (mean per case for both diagnoses, 6). In 9 instances (6.8%), the change was from positive (frozen) to negative (permanent) and in 43 (32.6%), from negative (frozen) to positive (permanent). There was poor agreement between frozen and permanent sections (kappa range per dermatopathologist, -0.1282 to 0.6615). If permanent histology is considered the "gold standard" for histologic evaluation, en face frozen sections are not suitable for accurate surgical margin assessment of melanocytic lesions.     

Heterotopic gastric mucosa involving the gallbladder and biliary tree

A case of heterotopic gastric mucosa in the common bile duct, cystic duct and gallbladder is reported in a 3-year-old girl with abdominal pain and jaundice. Abdominal US and CT showed dilatation of the biliary tree and a well-defined mass in the common bile duct that narrowed its lumen. The gallbladder was contracted in both examinations. The common bile duct and the gallbladder were resected and a choledochojejunostomy was performed. Although gastric heterotopy has been described throughout the entire length of the gastrointestinal tract, it is a very uncommon finding in the gallbladder and extremely rare in the biliary tree. A firm diagnosis of gastric heterotopia is based on the presence of fundal mucosa replete with parietal and chief cells. To our knowledge, this is the fifth reported case of heterotopic gastric tissue within the common bile duct, and the first to describe the US and CT findings. A relevant literature review and brief outline of the histological and radiological features are included in the discussion.     

The clinical use of gabapentin in bipolar spectrum disorders

BACKGROUND: with increasing awareness of lithium's limitations, several new anticonvulsants had been tested for their mood stabilisation during recent years. Among the innovative third generation mood stabilizing anticonvulsants, gabapentin (GBP) seems to have a broad spectrum of efficacy, although no certain data are available as to its efficacy and use in clinical practice. Accordingly, an extensive review on this subject has been carried out. METHODS: A computer-generated search of the biomedical literature and abstract books of the more important scientific psychiatric congresses until June 2000 was undertaken to identify all pertinent case reports, case series and studies of GBP as monotherapy or adjunctive therapy in mood disorders. We identified 40 open-label studies on the use of GBP in at least 600 patients with bipolar disorder (BP), manic, depressed, or mixed episodes and unipolar depression and four controlled studies. RESULTS: The 40 open-label studies and two of the controlled trials suggested that GBP may have a role as adjunctive agent in the treatment of patients with bipolar disorders particularly when complicated by co-morbid anxiety disorder or substance abuse. GBP is usually very well tolerated and has no pharmacological interference with other mood stabilisers. However, in the other two double-blind studies GBP has not been found to be efficacious in the treatment of refractory mania or refractory bipolar depression. CONCLUSIONS: Although failing to show clear antimanic efficacy in randomized trials, gabapentin still remains a clinically useful agent when it comes to combination treatment in refractory and co-morbid patients.