CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long-lived inhibition of expression of peri-infarction depolarizing waves, possibly by altering potassium-channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.     

A rapid method for harvesting autologous red cells from patients with hemoglobin S disease

Red cells from patients with sickle cell disease (HbSS and HbSC) are more resistant to lysis in hypotonic NaCl solutions than normal (HbAA) red cells. Taking advantage of this inherent resistance to osmotic stress, patient red cells (HbSS or HbSC) were rapidly isolated from donor red cells (HbAA or HbAS) by washing with hypotonic (0.3%) NaCl. The hypotonic method of washing provides a previously unavailable means for obtaining autologous HbSS or HbSC red cells from samples containing transfused donor red cells. Once isolated, these red cells can be used for phenotyping, autoadsorption, or evaluation of positive direct antiglobulin tests.     

Van der Woude syndrome: dentofacial features and implications for clinical practice

Background:  Van der Woude syndrome (VWS) is the most common clefting syndrome in humans. It is characterized by the association of congenital lower lip fistulae with cleft lip and/or cleft palate. VWS individuals have a high prevalence of hypodontia. Although caused by a single gene mutation, VWS has variable phenotypic expression. This study aimed to describe the range of clinical presentations in 22 individuals with VWS to facilitate its diagnosis.
Methods:  A retrospective study of 22 patients with a diagnosis of VWS was undertaken at the Australian Craniofacial Unit (ACFU) in Adelaide. Three extended families with affected members were included in the study cohort.
Results:  The overall prevalence of lip pits in this study cohort was 86%. Cleft phenotypes included bilateral cleft lip and palate (32%); unilateral cleft lip and palate (32%); submucous cleft palate (23%); and isolated cleft hard and soft palate (9%). Missing permanent teeth were reported in 86% of affected individuals.
Conclusions:  Submucous cleft palate in VWS may go undiagnosed if the lower lip pits are not detected. Associated hypodontia and resultant malocclusions will also require management by a dental team.     

The impact of cytokines on the expression of drug transporters,cytochrome P450 enzymes and chemokine receptors in human PBMC

Background and purpose:

The function of transporters in peripheral blood mononuclear cells (PBMC) has been characterized, but less is known about cytochrome P450 (CYP) enzyme function in these cells. Given that cytokines are dysregulated in many diseases, the purpose of this work was to assess the impact of cytokines on the expression of CYPs, transporters and chemokine receptors in PBMC.

Experimental approach:

Human PBMC were incubated with cytokines for 48 h. ATP-binding cassette (ABC)B1, ABCC1, ABCC2, CYP2B6, CYP3A4, CXCR4 and CCR5 expression were measured by quantitative polymerase chain reaction and flow cytometry at 0, 4, 8, 24 and 48 h. Enzyme activity was assessed using fluorescent probes.

Key results:

We show here functional activity of CYP3A4 and CYP2B6 in PBMC. Furthermore, cytokines had a significant impact on the mRNA and protein expression of all proteins. For example, interleukin-2 (IL-2) had a marked impact on ABCB1 mRNA (% control 4745 ± 11961) and protein (% control 200 ± 57). Increases in drug efflux transporter expression, in response to cytokines, resulted in reduced cellular accumulation of digoxin [decrease of 17% and 26% for IL-2 and interferon-γ (IFNγ) respectively] and saquinavir (decrease of 28% and 30% for IL-2 and IFNγ respectively). The degree to which drug transporter and chemokine receptor expression changed in response to cytokines was positively correlated (e.g. ABCB1 and CXCR4, r² = 0.545).

Conclusions and implications:

These data have important implications for diseases in which cytokines are dysregulated and for which pharmacological intervention targets immune cells.     

Adenocarcinoma of the gastroesophageal junction after bariatric surgery

BACKGROUND: The development of upper gastrointestinal malignancies after bariatric surgery has not been well characterized. Our objective was to review the experience of patients with distal esophageal cancer that was diagnosed after bariatric surgery. METHODS: A retrospective review was conducted to identify patients who had undergone bariatric surgery (1999 to 2006) and who later developed high-grade dysplasia or adenocarcinoma of the distal esophagus. RESULTS: Three patients (of 2,875 [0.1%]) developed esophageal cancer: 2 after Roux-en-Y gastric bypass and 1 after vertical banded gastroplasty. All three patients had complaints of reflux, and two were treated with esophagectomy. The third patient presented with invasive carcinoma and died 2 years after diagnosis. CONCLUSIONS: Our findings emphasize the importance of precise endoscopic evaluation before bariatric surgery in patients with gastroesophageal reflux disease (GERD), of the necessity for continuing postsurgical surveillance in patients with known Barrett's esophagitis, and of early evaluation in patients who develop new symptoms of GERD after bariatric surgery.     

Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis of 3851 patients

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) have a poorly defined natural history, and a staging system is not available. The objective of this study was to identify factors predicting survival after pancreatectomy for PNETs and to establish a postresection prognostic score. PATIENTS AND METHODS: From the National Cancer Data Base (1985-2004), patients were identified who underwent PNET resection. Multivariable Cox proportional hazards modeling was used to assess the impact of patient, tumor, treatment, and hospital factors on survival. A prognostic score based on the predictive factors from the Cox model was developed. RESULTS: Three thousand eight hundred fifty-one patients underwent resection for PNETs. Five-year overall survival was 59.3%, and the 10-year survival was 37.7%. On multivariable analysis, age, grade, distant metastases, tumor functionality, and type of resection were independent predictors of survival after resection of PNETs (P < 0.0001). Gender, race, socioeconomic status, tumor size, nodal status, margins, adjuvant chemotherapy, and hospital volume were not associated with survival. Age, grade, and distant metastases were the most significant predictors of survival and were incorporated into a PNET postresection prognostic score. The prognostic score correlated with outcomes and offered excellent survival discrimination by each of the 3 score subgroups: 76.7%, 50.9%, and 35.7% (P < 0.0001). The concordance index was 0.63 (95% CI 0.59-0.67), indicating reasonable agreement between actual outcomes and that predicted by the prognostic score. CONCLUSIONS: The prognostic score can be used to predict outcomes, guide adjuvant treatment, and stratify patients for clinical trials.     

STRESS FRACTURES OF THE FEMORAL SHAFT IN MILITARY RECRUITS

Stress fractures amongst military recruits are limited to the lower extremities; yet involvement of the shaft of the femur is unusual. Seven such cases in a series of 352 stress fractures are presented. The importance of early recognition and management is emphasized with a view to prevent bony disruption in an otherwise easily treatable condition.KEY WORDS: Fractures stress, Femoral fractures     

Biliary drainage of the common bile duct with an enteral metal stent

In this case report we present an elderly patient who was referred to our hospital with recurrent episodes of cholangitis that persisted after placement of five metal stents for a distal common bile duct （CBD） stenosis.All metal stents were endoscopically removed from the CBD by forceps after balloon dilatation of the papilla. A profoundly dilated CBD with sludge and concrements was seen. To ensure adequate bile drainage an enteral metal stent was inserted in the CBD. This case shows that proximally migrated uncovered metal stents in the CBD can be safely removed endoscopically under certain circumstances. We suggest that in the case of a CBD drainage problem due to an extremely dilated CBD, placement of an enteral metal stent in the CBD could be considered, especially in patients who are unfit for surgery.