Synergistic activity of the novel des-fluoro(6) quinolone,garenoxacin (BMS-284756), in combination with other antimicrobial agents against Pseudomonas aeruginosa and related species

Non-fermentative Gram-negative bacteria (Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia and Acinetobacter spp.) are intrinsically less susceptible to many antimicrobial agents. Two-drug combinations have been used to treat infections caused by less susceptible pathogens. In this study, the antibacterial activity of garenoxacin (GARX) with non-quinolones was examined. The non-quinolones evaluated were cefepime (CEPI), imipenem (IMIP), aztreonam (AZTR), piperacillin-tazobactam (PIPC/TZ), amikacin (AMK), ceftazidime (CTAZ), trimethoprim-sulphamethoxazole (TMP/SMX) and ticarcillin-clavulanate (TICC/CA). Synergism was determined by time-kill analysis using GARX (at 2 x its MIC, not to exceed 4 mg/l) and the second drug (at 1 x MIC, not to exceed its susceptible MIC breakpoint), and is defined as > or = 2 log(10) enhanced killing at 24 h with the combination. Partial synergy is defined as > or = 1.5 log(10) but < 2 log(10) enhanced killing with the drug combination. Synergy/partial synergy was observed most often with GARX plus: CEPI, AZTR, PIPC/TZ, IMIP (five strains each) or AMK (four strains) vs. eight P. aeruginosa; CTAZ, AZTR (five strains each) vs. six B. cepacia; TICC/CA (six strains), CEPI, CTAZ or AMK (five strains each) vs. eight S. maltophilia; and CEPI, AMK (three strains each) or CTAZ, TICC/CA (two strains each) vs. four Acinetobacter spp. In conclusion, synergistic killing was observed frequently with GARX plus a non-quinolone bactericidal agents against non-fermentative Gram-negative bacteria, including strains intermediately susceptible/resistant to one or both agents.     

Mapping of the distribution of significant proteins and proteoglycans in small intestinal submucosa by fluorescence microscopy

Because small intestine submucosa (SIS) is a bioscaffold for tissue regeneration, we describe a method to analyze the material for growth peptides and for structural molecules. Immunofluorescence methods are described for relative quantification of abundant structural proteins. Additionally, a quantitative technique for comparison of the content of less abundant proteins in SIS was developed using the tyramide signal amplification (TSA) system that is applicable to paraffin-preserved tissue blocks. Frozen sections generally shredded when cut thinly enough to permit entry and washout of reagents. Five micrometer sections cut from paraffin blocks were immunolabeled for collagen, heparan sulfate proteoglycans (HSPG), FGF2, TGFbeta, and VEGF. Images of tissue sections were acquired by a linear image camera and quantified by densitometry after thresholding the signal to minimize nonspecific fluorescence. Immunohistochemistry was used to confirm the immunofluorescence methods. HSPG was widely distributed but concentrated in vessels. FGF2 was distributed diffusely and was associated with fibrous structures. VEGF was distributed mainly around vessels. TGFbeta was barely detectable above background. Collagen fibrils were distinctly present, and with a two-color fluorescence system, the distribution of components relative to collagen can be assessed. The anatomic structure of SIS is likely to play an important role in the regeneration of tissues, and factors in remnant vessels may facilitate penetration of the matrix along these avenues.     

The prevention and treatment of deep vein thrombosis

Deep vein thrombosis can have serious long-term consequences and can result in fatal complications. Many patients are at increased risk of DVT, but knowledge of common risk factors and an awareness of appropriate prophylactic measures can help prevent its occurrence. An ability to recognise common clinical signs and symptoms, together with an understanding of diagnosis and treatment, benefits the nursing management of DVT.     

Decision making for health care professionals: use of decision trees within the community mental health setting

AIM OF THE PAPER: To examine the application of the decision tree approach to collaborative clinical decision-making in mental health care in the United Kingdom (UK). BACKGROUND: While this approach to decision-making has been examined in the acute care setting, there is little published evidence of its use in clinical decision-making within the mental health setting. The complexities of dual diagnosis (schizophrenia and substance misuse in this case example) and the varied viewpoints of different professionals often hamper the decision-making process. This paper highlights how the approach was used successfully as a multiprofessional collaborative approach to decision-making in the context of British community mental health care. DESIGN: A selective review of the relevant literature and a case study application of the decision tree framework. CONCLUSIONS: The process of applying the decision tree framework to clinical decision-making in mental health practice can be time consuming and client inclusion within the process is not always appropriate. The approach offers a method of assigning numerical values to support complex multiprofessional decision-making as well as considering underpinning literature to inform the final decision. Use of the decision tree offers a common framework that can assist professionals to examine the options available to them in depth, while considering the complex variables that influence decision-making in collaborative mental health practice. Use of the decision tree warrants further consideration in mental health care in terms of practice and education.     

Smoking behavior of 226 patients with diagnosis of stage IIIA/IIIB non-small cell lung cancer

There is limited research of smoking cessation following diagnosis of lung cancer. This prospective study assessed cigarette smoking behavior among 226 patients (142 males, 84 females) prior to, at the time of, and after the diagnosis of unresectable stage IIIA/IIIB non-small cell lung cancer and entry into a phase III trial examining combined thoracic radiation therapy and chemotherapy. Their mean +/-S.D. age was 62.7+/-9.4 years and 95.6% were Caucasian. Of 215 patients with a history of cigarette smoking, 69% (148/215) stopped smoking prior to entry in the trial, 9% (20/215) stopped smoking at some point during the course of the trial, 11% (24/215) continued smoking throughout the trial, 7% (16/215) were smoking at baseline but did not report subsequent smoking status, and smoking status at study entry was missing for the remaining patients. The majority of lung cancer patients were able to stop smoking. A notable subset of patients continued smoking despite diagnosis of lung cancer, enrollment in a clinical trial, treatment-related toxicity, and encouragement from clinicians to stop smoking. Smoking cessation interventions are needed for lung cancer patients who continue to smoke.