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.     

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.     

Tissue disposition of 2'-O-(2-methoxy) ethyl modified antisense oligonucleotides in monkeys

This study examined the plasma pharmacokinetics, tissue distribution, and metabolism of three second generation antisense oligonucleotides in monkeys. Three groups of monkeys were treated with 10 mg/kg of each test compound by a single 2-h intravenous infusion. Oligonucleotide concentrations were measured in plasma, tissues, and urine using capillary gel electrophoresis (CGE). HPLC-MS was used to identify the metabolite(s) of the study compounds. Plasma-concentration-time profiles after infusion for the two phosphorothioate oligonucleotides were mono-exponential, but was bi- exponential for the phosphodiester oligonucleotide. Plasma clearance for the phosphodiester oligonucleotide was four- to sevenfold higher than the two phosphorothioate oligonucleotides, which was attributed to the plasma protein binding and reduced nuclease resistance. 2'-O-(2-methoxy) ethyl (MOE) modification at both 3' and 5' ends of a phosphorothioate oligonucleotide greatly enhanced the resistance to nucleases in plasma and tissue. MOE modification only at the 3' end enhanced the resistance to nucleases in plasma, but only moderately enhanced the resistance to nucleases in tissues. Urinary excretion was a minor elimination pathway for the phosphorothioate oligonucleotide, but was a major elimination pathway for the phosphodiester oligonucleotide. The results characterize the relationships between structure and disposition and will direct future modifications for therapeutic use.     

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer

OBJECTIVE: Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. METHODS: Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and overall survival rates were compared between women who were treated with (n = 41) and without (n = 53) PMRT. RESULTS: Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4% vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences (p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer-specific and overall survival rates. CONCLUSION: This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age <==50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.