Antiproliferative and apoptotic potencies of glucocorticoids: nonconcordance with their antiinflammatory and immunosuppressive properties

Relative antiinflammatory and immunosuppressive potencies of glucocorticoids (GC) were previously well defined. Nonetheless, GC also regulate cell proliferation and programmed death (apoptosis). The aim of this study was to determine the relative potency of different GC on the modulation of cell survival. The GC-sensitive lymphoblast cell line CEM-c7/14 was submitted to 48 h-exposure to GC (dose-response curve from 10(-8) to 10(-5) M). Cell survival was analyzed employing the DimethylTiazol-Tetrazolium (MTT) test. For each GC at least 4 experiments were performed in quadruplicate. Responses to different GC at the same molarity were analyzed by ANOVA on Ranks. Cell responses to the same GC in different concentrations were tested by repeated measures ANOVA. The EC50 for each GC was calculated with the GraphPad Prism 3.0 software. The use of low concentrations (10(-8) and 10(-7) M) of hydrocortisone and methylprednisolone determined a similar effects on cell survival, which was less prominent than that observed with betamethasone, budesonide or momethasone. Momethasone was the most potent GC, inducing the most intense dexamethasone reduction on cell survival at the lowest concentration (10(-8) M). Momethasone and methylprednisolone were the two GC with the strongest impact on cell survival. Our findings suggest that antiproliferative and apoptotic potencies of GC are different from those previously reported antiinflammatory and immunosuppressive actions.     

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Post-hypoxic myoclonus induces Fos expression in the reticular thalamic nucleus and neurons in the brainstem

Post-hypoxic myoclonus is a movement disorder characterized by brief, sudden involuntary muscle jerks. Although the mechanism underlying this disorder remains unclear, earlier pharmacological studies indicated that aberrant activity of specific neuronal circuitry in the central nervous system causes this disorder. In the present study, Fos protein, an immediate-early gene product, was used as a marker of neuronal activity to identify the brain nuclei possibly involved in post-hypoxic myoclonus. We found that Fos protein was immunologically detected in the reticular thalamic nucleus (RT), the medial longitudinal fasciculus (MLF) as well as in the locus coeruleus (LC) and the periventricular gray substance (PVG) in post-hypoxic rats that developed myoclonus in response to auditory stimuli. Fos was not detected in these nuclei from rats that underwent 4 min of cardiac arrest without myoclonus. Electrolytic lesions of the RT or MLF but not the LC/PVG significantly reduced auditory stimulated myoclonus in the post-hypoxic rats. The results suggest that neuronal activity in the RT and the MLF plays a contributing role in post-hypoxic myoclonus.     

Renal scintigraphy unraveled the diagnostic dilemma of antenatal hydronephrotic solitary kidney-crossed renal ectopia

On antenatal ultrasound assessment, an apparently solitary hydronephrotic kidney was identified, confirmed on postnatal ultrasound examination. More detailed postnatal investigations revealed the diagnosis of crossed renal ectopia.     

Focal FDG uptake in mediastinal brown fat mimicking malignancy: a potential pitfall resolved on PET/CT

OBJECTIVE: A potential source of false-positive FDG PET interpretations in oncologic imaging is FDG uptake in brown fat. The purpose of this study was to determine the prevalence, location, and appearance of hypermetabolic brown fat in the mediastinum. MATERIALS AND METHODS: All PET/CT scans obtained at our cancer institution from August to October 2003 were retrospectively reviewed for increased FDG uptake in the mediastinum localized to fat on CT. The following features were recorded: location, appearance, maximal standard uptake value (SUV(max)) of hypermetabolic mediastinal brown fat, and presence of extramediastinal brown fat. RESULTS: PET/CT scans were obtained in 845 oncologic patients. Fifteen patients (1.8%) with focal hypermetabolic mediastinal brown fat were identified: nine women and two men (age range, 27-79; mean, 55.1 years) and four children (age range, 5-16 years; mean, 10 years). Hypermetabolic mediastinal brown fat (mean SUV(max), 5.7) was more common in children (4/8) than in adults (11/837) and more common in women (9/372) than in men (2/465). Foci of hypermetabolic brown fat were localized to the paratracheal, paraesophageal, prevascular, and pericardial regions; interatrial septum; and azygoesophageal recess. Five patients had focal hypermetabolic brown fat isolated to the mediastinum. Ten patients also had extramediastinal hypermetabolic brown fat in the neck, thorax, and abdomen. There was no difference in the body weight (p = 0.876) or body mass index (p = 0.538) of patients with hypermetabolic brown fat compared with age- and sex-matched control subjects. CONCLUSION: Hypermetabolic brown fat can be localized to the mediastinum and manifests as focal increased FDG uptake. Knowledge of this potential pitfall and precise localization with fusion PET/CT are important in preventing misinterpretation as malignancy.     

Short-term in vivo wear of cross-linked polyethylene

BACKGROUND: Cross-linked polyethylene was developed to reduce volumetric wear in prosthetic joints. Hip simulator studies have shown promising results with regard to wear reduction. This study evaluated the short-term in vivo wear of a moderately cross-linked polyethylene. METHODS: Linear head penetration, as an assessment of in vivo polyethylene wear, was measured in two groups of patients after total hip replacement. Twenty-four hips received a conventional polyethylene insert and thirty-four, a cross-linked polyethylene liner; both inserts were manufactured by the same company. Linear and volumetric wear rates were measured on radiographs with use of a validated computer-assisted technique and were adjusted for patient-related factors. Patient activity was assessed by a computerized two-dimensional accelerometer worn on the ankle. RESULTS: Patients with a conventional polyethylene insert showed a mean linear wear rate of 0.13 mm per year and a mean volumetric wear rate of 87.6 mm(3) per year. The group with a cross-linked polyethylene liner showed a mean linear wear rate of 0.02 mm per year and a mean volumetric wear rate of 17.0 mm(3) per year. Wear in the group with cross-linked polyethylene was 81% lower than that in the group with conventional polyethylene (p < 0.00001). Accounting for differences in patient activity, the adjusted wear rates per million cycles for a patient weight of 70 kg were 53 mm(3) per million cycles for conventional polyethylene and 15 mm(3) per million cycles for cross-linked polyethylene, a 72% reduction (p = 0.0002). No factor, other than the type of polyethylene, was found to influence the difference in wear rates between the two groups. CONCLUSIONS: The results of this study are promising. The in vivo wear reduction with this cross-linked polyethylene is consistent with the predictions of hip simulator studies.     

Results after endoscopic treatment of postoperative upper gastrointestinal fistulas and leaks using combined Vicryl plug and fibrin glue

Background The incidence of clinically relevant anastomotic leaks after upper gastrointestinal surgery is approximately 4% to 20%, and the associated mortality is up to 80%. Depending on the clinical presentation, the treatment options include surgery, conservative treatment with or without external drainage or endoscopic treatment.Methods This report presents nine cases of anastomotic leaks or fistulae after surgery for upper gastrointestinal cancers that were treated by insertion of a Vicryl plug and sealing with fibrin glue. Under sedation, all nine patients underwent endoscopic lavage of the cavity at the site of anastomotic leakage. The entrance to the cavity then was filled with Vicryl mesh and sealed off with fibrin glue. After the procedure, the patients underwent endoscopy and a water-soluble contrast study for assessment of the result.Results Seven of the nine patients had complete healing of the anastomotic leak or fistula after one to two endoscopic treatments. In one case, the treatment failed immediately because of a large and direct tracheoesophageal fistula. Another patient experienced recurrent intrathoracic abscesses after initial technical success.Conclusions Postoperative upper gastrointestinal fistulas or anastomotic leaks can be managed successfully with little morbidity by means of endoscopic insertion of Vicryl mesh with fibrin glue, thereby avoiding repetitive major surgery and its associated risks.     

Chorea and related disorders

Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham's chorea is the most common form of childhood chorea, whereas Huntington's disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.