Role of Tris-CaEDTA as an adjuvant with nebulised tobramycin in cystic fibrosis patients with Pseudomonas aeruginosa lung infections: A randomised controlled trial

BackgroundWe tested if disrupting iron utilisation by P. aeruginosa by adding the Tris-buffered chelating agent CaEDTA to nebulised tobramycin would enhance bacterial clearance and improve lung function in CF patients.MethodsIn this double-blind, randomised controlled trial, 26 episodes (25 patients) with P. aeruginosa infection admitted to two CF centres for treatment of an acute pulmonary exacerbation were randomly assigned to receive either 75 mg CaEDTA in Tris-buffered saline or placebo (Tris-buffered saline) nebulised in combination with 250 mg tobramycin twice daily for six weeks followed with four week safety follow-up. Primary endpoints were safety, tolerability, and bacterial density of P. aeruginosa. A secondary endpoint was lung function.ResultsThe study drug was well tolerated with adverse events comparable in both groups. The mean (SD) reduction in sputum P. aeruginosa count (log₁₀ CFU/g) in the CaEDTA vs placebo group was 2·05 (2·57) vs 0·82 (2·71) at two weeks relative to admission (p = 0·39). The mean improvement in ppFEV₁ was 16 vs 5 (p = 0·16); 11 vs 2 (p = 0·28); and 6 vs 2 percentage points (p = 0·47) at two, six, and ten weeks in CaEDTA and placebo groups, respectively.ConclusionsIn this pilot study in CF patients, an increase in the reduction of sputum density of P. aeruginosa and an increase in ppFEV₁ was observed in the group of patients who received Tris-CaEDTA added to inhaled tobramycin compared to the group who received inhaled tobramycin alone, although these differences were not statistically significant. The treatment was also shown to be safe.     

Physician Response to Prenatal Substance Exposure

Objectives: To examine physician responses to suspected prenatal substance exposure and the reasons underlying these responses. Methods: National mail survey of practicing obstetricians and pediatricians who see neonates. Response rate: 63%. Results: More than 70% of physicians reported having ever suspected prenatal substance exposure. Response rates did not vary by specialty. Twenty-seven percent reported that they had never suspected prenatal substance exposure. The most common lifetime pattern (60%) was some response whenever prenatal substance exposure was suspected; next most common was no suspicion (27%). Just over 10% had a discretionary response: acting in some cases of suspected prenatal substance exposure but ignoring others. Two percent consistently ignored their suspicions. Getting help for the patient and protecting the fetus were the most common reasons to act. Among those who had ignored their suspicions, lack of sufficient evidence of substance use was the most often cited reason. There were some important specialty differences in reasons for response and non-response and in specific responses likely to be taken. Obstetricians are far more likely to provide the patient with information and get a substance use history; pediatricians are more inclined to involve outsiders. Conclusions: Obstetricians and pediatricians seem quite willing to act on their suspicions of prenatal substance exposure, and generally respond by taking positive actions. Specialty differences are few and reflect practice differences.     

Contaminant Assimilation Within the Water Column of Two Newly Created Prairie Wetlands

This research examined the influence of abiotic factors on contaminant assimilation within the water column of two wetlands (RMA3 and RMA4) located on Rocky Mountain Arsenal National Wildlife Area, north of Denver, Colorado, USA. We define contaminant assimilation as the ability of a wetland system to reduce negative impacts of contaminants on aquatic organisms. To examine the influence of abiotic factors (i.e., alkalinity, suspended solids), chronic toxicity tests were performed from February 1992 through November 1993. Ceriodaphnia dubia were exposed to water from the wetlands, which was spiked with Zn. These tests indicated higher assimilative capacity in wetland RMA4 relative to RMA3. Dissolved organic carbon (DOC) was significantly greater in RMA4 than in RMA3, suggesting that it may have influenced differences in bioavailability of Zn in wetland water. Suspended solids were also consistently higher in RMA4 than in RMA3. To test the influence of suspended solids on contaminant assimilation, C. dubia were exposed to filtered and unfiltered Zn-spiked water from RMA4. The greater toxicity of Zn to C. dubia in filtered water indicated that suspended solids were important in ameliorating impacts of Zn in RMA4. Results from this study suggest that from the suite of variables assessed, DOC and suspended solids were the most important physiochemical influences on Zn toxicity within the water column of these two wetlands. Differences in habitat characteristics of RMA3 and RMA4 demonstrated the importance of site-selection toward functional design of wetlands. Received: 24 November 1997/Accepted: 14 September 1998     

What determines geographical variation in rates of acceptance onto renal replacement therapy in England?

OBJECTIVE: To determine the independent effects of need and supply factors on the known geographical variation in acceptance rates onto renal replacement therapy (RRT) in England. METHODS: Data were obtained from all renal units in England on the characteristics of all cases aged 16 years and over, resident in England, who were accepted onto RRT in 1991 and 1992. Of these, 5715 (94.5%) had a valid postcode that could be matched to a census ward. Multilevel modelling using Poisson regression was used. The number of acceptances in each census ward within age bands 16-34, 35-64 and 65+ was the dependent variable. Independent effects modelled were: (1) individual factors (age, sex); (2) census ward need factors--ethnicity (expressed as the percentage of the ward population that was Asian or African-Caribbean), socio-economic deprivation--and supply factors--'access' to the nearest renal unit using crowfly and road travel time and distance, and services available to each ward expressed as number of haemodialysis stations per 100,000 catchment population of the nearest renal unit; (3) district health authority level effects. RESULTS: Age was a major determinant of acceptance, with a 7-fold higher rate in males aged over 64 years compared with younger men. Acceptance rates were lower in females, with a negative age-sex interaction in females aged over 64 years. The percentage of both Asian and African-Caribbean populations per ward was a highly significant positive determinant. Deprivation was also a significant determinant, best represented by a customised index. There was an inverse relation of acceptance with distance, especially road travel time. Other supply side variables had a significant effect though there was no independent district effect. There was some variation in the strength of these relationships by type of area (Greater London, urban and non-urban). CONCLUSIONS: Need and supply factors influence service use as expressed as acceptance onto RRT. Pressure to expand RRT services needs to be aimed at areas with large minority ethnic populations and those living far from existing units.     

Detecting hepatic lesions: the added utility of CT liver window settings

PURPOSE: To prospectively evaluate the utility of adding computed tomographic (CT) liver windows to conventional soft-tissue windows for the detection of hepatic disease. MATERIALS AND METHODS: One of four radiologists experienced in abdominal imaging interpreted 1,175 consecutive abdominal CT scans from one institution. Hepatic images were first interpreted by using standard soft-tissue windows. The number of lesions and confidence in lesion detection were recorded. The liver-window images were then interpreted in conjunction with the soft-tissue-window images, and the number of lesions and confidence in detection were recorded again. The proportion of patients in whom additional lesions were found by using liver windows was determined. RESULTS: On soft-tissue-window and liver-window scans interpreted together, 869 (74%) patients had no hepatic lesions. Thirty-six (3.1%) patients had new lesions seen with the addition of liver windows. Twelve of these 36 patients had no lesions seen on soft-tissue-window scans. Twenty-six of the 36 patients with additional lesions seen had a history of neoplasm. There was a change in diagnosis in 1.7% of the patients with the addition of liver windows and a change in recommendation for follow-up in 0.85%. CONCLUSION: Routine interpretation of liver-window scans for all abdominal CT scans has limited added utility in detecting hepatic disease.     

Effects of cis-diamminedichloroplatinum (CDDP) on HeLa cell non-histone nuclear proteins

Summary Two-dimensional isoelectric focusing and sodium dodecyl sulfate (SDS) gel electrophoretic analyses of successive salt extracts of purified HeLa cell nuclei were used to study the effects of cis-diamminedichloroplatinum (CDDP) (cisplatin) on the synthesis and extractability of nuclear non-histone proteins. Nuclei were extracted sequentially with 0.025 M NaCl-0.075 M EDTA, 0.01 M Tris, and 0.6 M NaCl. Each fraction contained 100–400 polypeptide spots, only a few of which were affected by a 3.5-h CDDP pretreatment of the cells. The biosynthesis and/or metabolism of four polypeptide spots was significantly affected by the CDDP treatment. These polypeptides included: (a) 36K/5.8 (designated by MW/PI) in the 0.025 M NaCl-0.075 M EDTA extract, which decreased in intensity with treatment at 10 g CDDP/ml; (b) polypeptide spots 50K/6.0 and 45 K/5.3 in the Tris extract, which increased in intensity over a range of CDDP concentrations of 0–5 g CDDP/ml; and (c) a polypeptide complex at 110K/7.7 in the 0.6 M Na Cl extract, which decreased in intensity at CDDP concentrations of 0–5 g CDDP/ml. Scanning densitometry of the protein spots of the 0.6 M NaCl extract demonstrated that the 110K/7.7 complex decreased to half its intensity compared with non-drug-treated controls at a CDDP concentration of 0.9 g CDDP/ml. We have found that high-resolution two-dimensional gel electrophoretic analysis of nuclear proteins is a valuable technique for studying the effects of cytotoxic agents on the synthesis and/or extractability of specific cellular proteins.Abbreviations used in this paper are CDDP cis-diamminedichloroplatinum (II) - SDS sodium dodecyl sulfate     

Coping with Domestic Violence: Control Attributions,Dysphoria, and Hopelessness

We investigated the influence of control judgments and coping style on emotional reactions to domestic violence utilizing the framework of hopelessness theory. We assessed abuse severity, control attributions, coping, dysphoric symptoms, and hopelessness in 70 battered women recruited from 12 domestic violence agencies. Respondents reported dysphoria but not hopelessness. Increased reports of dysphoria were associated with higher levels of self-blame and avoidance coping and lower levels of problem-focused coping. Increased problem-focused coping was associated with decreased hopelessness. Perceived control over current abuse was not related to dysphoria. High expectations for control over future events were associated with decreased dysphoria. We discuss our results in terms of their application to attributional accounts of emotional reactions to battering.     

Critical decisions in the management of endoscopic perforations of the colon

The ideal management of suspected colon perforation following colonoscopy remains elusive because the incidence is only 0.1 to 2.0 per cent. The patient with obvious perforation deserves immediate exploration, but the patient with equivocal findings poses a diagnostic dilemma. We propose an algorithm based on the results of water-soluble contrast enema that allows for rapid, definitive surgical decision-making. If perforation is confirmed, early operation allows for primary repair without resection or colostomy, or if no perforation is identified, medical management can be undertaken with confidence. This algorithm should ensure that the surgical management of this potentially lethal complication is not unnecessarily delayed.     

Bioterrorism risk perceptions and educational needs of public health professionals before and after September 11, 2001: a national needs assessment survey.

The study objectives were to compare local public health professionals' bioterrorism risk perceptions, the extent of bioterrorism preparedness training, and to describe preferred methods for delivery of preparedness education in the United States. National needs assessments were conducted via a mailed survey to 3,074 local public health departments in October 2000 and November 2001. Compared to a survey conducted in October 2000, the perceived risk of a bioterrorism attack in the United States increased dramatically after September 11 (p < 0.0001); however, 57% of respondents believed one was unlikely to occur within their own community. Public health professionals perceive their own communities to be at low risk for a bioterrorism event. Ongoing, updated, standardized bioterrorism preparedness education is needed.