Obstructive biliary ascariasis with cholangitis and hepatic abscesses in Laos: a case report with gall bladder ultrasound video

A 12-year-old Lao boy with obstructive biliary Ascaris infection is described and video of the gallbladder ultrasound presented. The patient developed severe complications of obstructive cholangitis, a large right pleural effusion and hepatic abscesses requiring prolonged antibiotic therapy. The differential diagnosis of worms in the gall-bladder is discussed.     

Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia

Primary infection with herpes simplex virus 1 (HSV-1) and varicella zoster virus (VZV) results in lifelong latent infections of neurons in sensory ganglia such as the trigeminal ganglia (TG). It has been postulated that T cells retained in TG inhibit reactivation of latent virus. The acquisition of TG specimens of individuals within hours after death offered the unique opportunity to characterize the phenotype and specificity of TG-resident T cells in humans. High numbers of activated CD8(+) T cells expressing a late effector memory phenotype were found to reside in latently infected TG. The T cell infiltrate was oligoclonal, and T cells selectively clustered around HSV-1 but not VZV latently infected neurons. Neuronal damage was not observed despite granzyme B expression by the neuron-interacting CD8(+) T cells. The TG-resident T cells, mainly CD8(+) T cells, were directed against HSV-1 and not to VZV, despite neuronal expression of VZV proteins. The results implicate that herpesvirus latency in human TG is associated with a local, persistent T cell response, comprising activated late effector memory CD8(+) T cells that appear to control HSV-1 latency by noncytolytic pathways. In contrast, T cells do not seem to be directly involved in controlling VZV latency in human TG.     

Profiling signaling polarity in chemotactic cells

Cell movement requires morphological polarization characterized by formation of a leading pseudopodium (PD) at the front and a trailing rear at the back. However, little is known about how protein networks are spatially integrated to regulate this process at the system level. Here, we apply global proteome profiling in combination with newly developed quantitative phosphoproteomics approaches for comparative analysis of the cell body (CB) and PD proteome of chemotactic cells. The spatial relationship of 3,509 proteins and 228 distinct sites of phosphorylation were mapped revealing networks of signaling proteins that partition to the PD and/or the CB compartments. The major network represented in the PD includes integrin signaling, actin regulatory, and axon guidance proteins, whereas the CB consists of DNA/RNA metabolism, cell cycle regulation, and structural maintenance. Our findings provide insight into the spatial organization of signaling networks that control cell movement and provide a comprehensive system-wide profile of proteins and phosphorylation sites that control cell polarization.     

Quantification of reduced health-related quality of life in patients with rheumatoid arthritis compared to the general population

OBJECTIVE: To compare levels of health-related quality of life (HRQOL) among patients with rheumatoid arthritis (RA) to those of the general population. METHODS: Disease burden was assessed using a generic health status instrument (Medical Outcome Study Short Form-36) for measurements of HRQOL and SF-6D to calculate utility scores in representative patients aged 20 to 79 years from the Oslo RA Register (n = 1052), and in individuals in the general population (n = 2323). Comparisons were performed with respect to sex and age, and standardized difference scores (s-scores) were calculated for comparisons with the norm. RESULTS: HRQOL in patients with RA was reduced compared to the general population on all scales of the SF-36 for both males and females and for all age groups. s-scores adjusted for age and education ranged from -1.39 for physical functioning to -0.27 for mental health. The overall difference in utility was 0.16 and ranged from 0.13 (in female patients below 50 yrs) to 0.20 (patients 50-60 years). This implies that RA of 1 year duration entails a disease burden of 14-20 quality-adjusted life-years in 100 RA patients. CONCLUSION: RA inflicts a substantial disease burden, and the disease affects all HRQOL dimensions as measured by the SF-36 in both sexes and in all age groups. Physical functioning is predominantly affected, but RA has social and mental consequences.     

Clinical Characteristics and Outcomes in Patients with Advanced Rectal Cancer: A National Prospective Cohort Study

Purpose At the time of diagnosis, approximately one third of patients with rectal cancer present with advanced disease. In this study we focus on a group of patients with primary advanced rectal cancer considered as not operable. We address various clinical aspects relevant for decision-making in a group of patients in need of palliative care. Methods Between January 1997 and December 2001, 4831 consecutive patients with rectal cancer were prospectively registered in the Norwegian Rectal Cancer Registry. In this national population-based cohort, 386 patients (8 percent) without surgical interventions were identified. These patients comprise the study population. Clinical characteristics and survivals were addressed. Results Patients not surgically treated were significantly older compared with other treatment groups (median age, 80 years; interquartile range, 72–86 vs. median age, 71 years; interquartile range, 62–79 years) (P<0.001). Median survival time was 4.5 (range, 3.5–5.4) months, regardless of age, gender, or hospital category. Patients who received radiotherapy had a significantly increased survival (P<0.001) compared with patients not treated with radiation, with a median survival time of 10.2 (range, 7.3–12.1) months vs. 2.8 (range, 2.1–3.6) months, respectively. Use of chemotherapy was not associated with improved survival. In multivariate analysis, only stage of disease and radiotherapy were independent predictors of better survival. Conclusion Higher age and comorbidity seem to influence choice of treatment in this subgroup of patients with advanced rectal cancer disease. In nonsurgically treated patients, radiotherapy was associated with an improved survival. Our prospective, population-based cohort study emphasizes the dismal prognosis of these patients, which also should challenge our efforts and clinical approaches in palliative care. Dr. H. K. Sigurdsson, M.D., is a Reseach Fellow sponsored by the Western Norwegian Regional Health Authorities (Project No. 911158). Reprints are not available.     

The effect of vagal cooling on canine hepatic glucose metabolism in the presence of hyperglycemia of peripheral origin

We examined the role of vagus nerves in the transmission of the portal glucose signal in conscious dogs. At time 0, somatostatin infusion was started along with intraportal insulin and glucagon at 4-fold basal and basal rates, respectively. Glucose was infused via a peripheral vein to create hyperglycemia ( approximately 2 fold basal). At t = 90, hollow coils around the vagus nerves were perfused with -10 degrees C or 37 degrees C solution in the vagally cooled (COOL) and sham-cooled (SHAM) groups, respectively (n = 6 per group). Effectiveness of vagal blockade was demonstrated by increase in heart rate during perfusion in the COOL vs SHAM groups (183 +/- 3 vs 102 +/- 5 beats per minute, respectively) and by prolapse of the third eyelid in the COOL group. Arterial plasma insulin (22 +/- 2 and 24 +/- 3 micro U/mL) and glucagon (37 +/- 5 and 40 +/- 4 pg/mL) concentrations did not change significantly between the first experimental period and the coil perfusion period in either the SHAM or COOL group, respectively. The hepatic glucose load throughout the entire experiment was 46 +/- 1 and 50 +/- 2 mg . kg(-1) . min(-1) in the SHAM and COOL groups, respectively. Net hepatic glucose uptake (NHGU) did not differ in the SHAM and COOL groups before (2.2 +/- 0.5 and 2.9 +/- 0.8 mg . kg(-1) . min(-1), respectively) or during the cooling period (3.0 +/- 0.5 and 3.4 +/- 0.6 mg . kg(-1) . min(-1), respectively). Likewise, net hepatic glucose fractional extraction and nonhepatic glucose uptake and clearance were not different between groups during coil perfusion. Interruption of vagal signaling in the presence of hyperinsulinemia and hyperglycemia resulting from peripheral glucose infusion did not affect NHGU, further supporting our previous suggestion that vagal input to the liver is not a primary determinant of NHGU.     

Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children

OBJECTIVE: The study aimed to determine the cognitive effect of the Val108/158Met polymorphism in the catechol-O-methyltransferase (COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. METHOD: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children (ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function--including working memory, verbal and motor inhibition, attentional control, and IQ--were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. RESULTS: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. CONCLUSIONS: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia.