Intravenous colistin sulphomethate in acute respiratory exacerbations in adult patients with cystic fibrosis

BACKGROUND: Patients with cystic fibrosis have received more intravenous antibiotic courses as median survival has steadily increased. A number of centres have adopted a policy of regular (three monthly) rather than on demand intravenous antipseudomonal antibiotics. More widespread bacterial antibiotic resistance has resulted from this increased antibiotic use. Most Pseudomonas aeruginosa strains remain fully sensitive to colistin but its use has been resisted owing to concerns about neurotoxicity and nephrotoxicity. A study was carried out to assess the safety and efficacy of intravenous colistin in the treatment of acute respiratory exacerbations in adult patients with cystic fibrosis. METHODS: Patients with chronic Pseudomonas aeruginosa colonisation who presented with protocol defined respiratory tract exacerbations were randomised to receive treatment for 12 days with either colistin (2 MU tds intravenously) alone or with a second anti- pseudomonal antibiotic. Comparisons of the absolute values of respiratory function tests on days 1, 5, and 12 and of overnight oxygen saturation on days 1 and 12 were the primary outcome measures. Patient's weight, clinical and chest radiographic scores, and peripheral blood markers of inflammation were also documented. The effect of each treatment regimen individually was assessed by the change in clinical measurements from baseline values. Adverse renal effects were monitored by measurement of serum levels of urea and electrolytes, creatinine clearance, and ward urine testing. Neurotoxicity was monitored by direct questioning for symptoms. RESULTS: Fifty three patients, 18 of whom entered the study twice, were enrolled. The mean forced expiratory volume in one second (FEV1) increased significantly in both groups, mean forced vital capacity (FVC) only with dual therapy. Both groups showed a non-significant increase in overnight oxygen saturation. All patients showed clinical improvement. Thirty seven adverse neurological events (two severe) were reported in 33 patients in the monotherapy group and 37 (none severe) in 36 patients in the dual therapy group. One patient withdrew because of severe weakness and dizziness. All other adverse neurological events were well tolerated and resolved during or shortly after treatment. Significant changes were seen in mean serum urea levels in both groups, but in only four patients to a level above the normal range, and in creatinine clearance in the dual therapy group. At 24 month follow up no long term adverse consequences from intravenous colistin were found in patients who completed the study. CONCLUSIONS: Intravenous colistin is an effective treatment for Pseudomonas aeruginosa associated pulmonary exacerbations in patients with cystic fibrosis. Assessment of the individual effect of each treatment regimen suggests a greater efficacy when colistin is combined with a second antibiotic to which the pseudomonas shows in vitro sensitivity. Changes in renal function should be monitored.


     

Favorable outcome of neonatal aortic thrombosis and renovascular hypertension

Fifteen children with renovascular hypertension as a result of aortic thrombosis were followed for a mean of 26 months (range 5 to 58 months) to determine outcome. As neonates, all patients had hypertension and elevated plasma renin activity. Of 11 patients studied with radionuclide renography and scintigraphy, 10 had abnormal renal blood flow; three had complete absence of unilateral perfusion. On follow-up examination all children were normotensive; five children ages 5 to 24 months required antihypertensive medication. Of 15 children, 14 had normal statural growth; all had normal serum creatinine, plasma renin activity, and calculated glomerular filtration rate values. Patients with complete absence of renal perfusion unilaterally remained functionally anephric; children with less severe perfusion deficits had improved perfusion as shown by radionuclide renography and scintigraphy. We believe that many patients with aortic thrombosis and renovascular hypertension who have had aggressive antihypertensive therapy in the neonatal period will have good renal function and increased perfusion to the affected kidney 2 years later.     

Neuropsychological Performance and Treatment Outcome in Male Alcoholics

Commonly used neuropsychological tests were administered to 91 detoxified alcoholics at the beginning of treatment. Statistically significant relationships were observed between test scores and post treatment consumption determined 8 months after completing treatment for 72 patients. The results varied depending upon the particular measure of posttreatment consumption evaluated and the type of statistical analysis used. The most consistent relationships were often counter to the notion that increased neuropsychological performance is correlated with a more favorable treatment outcome. Neuropsychological evaluation is of limited clinical utility in predicting posttreatment alcohol consumption.     

Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

Voltage-dependent priming of rat vanilloid receptor: effects of agonist and protein kinase C activation

The responses of vanilloid receptor (VR) channels to changing membrane potential were studied in Xenopus oocytes and rat dorsal root ganglion (DRG) neurons. In oocytes, capsaicin-evoked VR currents increased instantaneously upon a step depolarization and thereafter rose biexponentially with time constants of ≈20 and 1000 ms. Similarly, upon repolarization the current abruptly decreased, followed by a biexponential decay with time constants of ≈4 and 200 ms. Qualitatively similar effects were observed in single channel recordings of native VR channels from DRG neurons and with endogenous VR activators, including heat (43 °C), H⁺, anandamide and protein kinase C (PKC). The magnitude of the time-dependent current rise increased with membrane depolarization. This effect was accompanied by an increase in the relative proportion of the fast kinetic component, A ₁. In contrast, the time constants of the activation and deactivation processes were not strongly voltage dependent. Increasing the agonist concentration both reduced the magnitude of the current rise and increased its overall rate, without significantly altering the deactivation rate. In contrast, PKC both speeded the current rise and slowed its decay. These results suggest that voltage interacts with agonists in a synergistic manner to augment VR current and this mechanism will be enhanced under conditions of inflammation when VRs are likely to be phosphorylated.     

Treatment of resistant distal intestinal obstruction syndrome with a modified antegrade continence enema procedure

We report a case of a patient with CF who had a long history of recurrent distal intestinal obstruction syndrome. She had been treated with conventional treatment including gastrografin, n-acetyl cysteine, Klean prep and Picolax. She underwent a modified antegrade continence enema procedure. She currently irrigates her conduit every 2-3 days. She has had no further symptoms of distal intestinal obstruction syndrome.     

Indoor nitrogen dioxide and childhood respiratory illness

Abstract: Nitrogen dioxide is produced from the combustion of fossil fuels and as an emission from gas-fired appliances, and is also a component of tobacco smoke. Nitrogen dioxide has been shown in experimental animals to be toxic to the respiratory tract. A number of recent studies have suggested that children exposed to significant levels of nitrogen dioxide in the home may be more susceptible to respiratory illness than children exposed to normal ambient levels. Respiratory illness is a major cause of morbidity in children everywhere. Here, we review the available evidence of this association and explore methodological issues in measurement of nitrogen dioxide exposure— misclassification of subjects, symptom bias and confounding. It has recently been shown that some New South Wales school rooms, where unflued gas heaters are often used as a source of warmth, have nitrogen dioxide levels which are above recommended ambient levels for outside air. This has underlined the need for setting standards for indoor levels of various pollutants, and cohort studies are suggested, to include personal monitoring and prospective data collection techniques.     

The "well tempered" diuretic renogram: a standard method to examine the asymptomatic neonate with hydronephrosis or hydroureteronephrosis. A report from combined meetings of The Society for Fetal Urology and members of The Pediatric Nuclear Medicine Council--The Society of Nuclear Medicine.

Perinatal hydronephrosis (HN) and hydroureteronephrosis (HUN) are recognized more frequently as the routine use of prenatal ultrasonography increases. The decision-making process for those instances of urinary tract dilatation that require surgical correction and those that do not is based in part on the findings of diuresis renography. The methodology for performing this test has differed among nuclear medicine practitioners and the surgical findings are occasionally discrepant from the diuretic renogram interpretation. Consequently, the Society of Fetal Urology (SFU) and the Pediatric Nuclear Medicine Council (PNMC) of the Society of Nuclear Medicine met to develop by consensus a more uniform methodology. A standard method has been agreed upon for the following facets of diuretic renography: patient preparation (hydration and bladder catheterization), diuresis renography technique (radiopharmaceutical used, patient position during examination, data acquisition parameters, diuretic pharmaceutical and dosage, time of injection and regions of interest to monitor diuretic effect), and data analysis (percent differential renal function, curve pattern analysis and methods of measuring diuretic response). Pooled diuresis renogram data are being collected for analysis for correlation with surgical results and clinical outcomes to determine the most appropriate information to be derived from the diuretic renogram in neonates with HN and HUN.