Dimensions and disorder specificity of impulsivity in pathological gambling

Impulsivity is a core characteristic of pathological gambling (PG), even though the underlying structure and disorder specificity is unclear. This study aimed to explore different dimensions of impulsivity in a clinical sample including PG. Furthermore, we aimed to test which alterations of the impulsivity-related dimensions are disorder specific for PG. Participants were individuals diagnosed with PG (n = 51) and two groups also characterized by various impulsive behaviors: an alcohol dependence (AD; n = 45) and a Gilles de la Tourette syndrome (GTS; n = 49) group. A healthy control (HC; n = 53) group was recruited as comparison group. A comprehensive assessment was used including impulsivity-related and antipodal parameters of the Stop Signal Task, Stroop Task, Tower of London Task, Card Playing Task, Iowa Gambling Task and the Barratt Impulsiveness Scale-11. Principal axis factor analysis revealed four impulsivity-related dimensions that were labeled ‘self-reported impulsivity’, ‘prepotent response impulsivity’, ‘choice impulsivity’ and ‘motor impulsivity’. The PG group scored significantly higher on all four dimensions compared to the HC group. In contrast, the PG group did not differ on any of the dimensions from the AD or the GTS group, except for ‘choice impulsivity’ where the PG group exhibited higher factor scores compared to the GTS group. Altogether, PG is associated with generally heightened impulsivity profiles compared to a HC group, which may be further used for intervention strategies. However, heightened scores in the impulsivity dimensions are not disorder specific for PG. Further research on shared or different underlying mechanisms of these overlapping impulsivity impairments is necessary.     

Risk factors for tuberculosis in older children and adolescents: a matched case–control study in Recife,Brazil

Background

Tuberculosis is a major disease worldwide and most research focus on risk factors for adults, although there is a marked adolescent peak in incidence. The objective of this study was to identify risk factors for tuberculosis in children aged 7 to 19.

Methods

A case control study matched by age with 169 cases and 477 controls. The study population consisted of adolescents and older children from Recife, Brazil. Cases were individuals diagnosed with tuberculosis in the control programme and controls were selected in the neighborhood of cases. Conditional logistic regression was used to identify risk factors.

Results

Cigarette smoking increased by 50% the risk of tuberculosis but that this was not statistically significant (OR?=?1.6). Other risk factors were sleeping in the same house as a case of tuberculosis (OR?=?31.6), living in a house with no piped water (OR?=?7.7) (probably as a proxy for bad living conditions), illiteracy (OR?=?3.7) and male sex (OR?=?1.8). The increase in risk with living in houses with no piped water was much more marked in males. The proportion of cases of tuberculosis attributed to contact with someone with TB was 38% and to illiteracy, lack of piped water and smoking, 20%.

Conclusion

Household contact with tuberculosis, social factors and male sex play the biggest role in determining risk of TB disease among children and adolescents in the study. We recommend further research on the relationship of cigarette smoking on tuberculosis in adolescents, and on whether the sex differentials are more marked in bad living conditions. Separate studies should be conducted in older children and in adolescents.

     

Differential coupling of CC chemokine receptors to multiple heterotrimeric G proteins in human interleukin-2-activated natural killer cells

Using two different approaches, we have investigated the types of G proteins coupled to CC chemokine receptors. First, permeabilization of interleukin-2-activated natural killer (IANK) cells with streptolysin-O and introduction of anti-G protein antibodies inside these cells resulted in the following. (1) Anti-G(s), anti-G(o), and anti-G(z) inhibited the migration of IANK cells in response to macrophage- inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), or regulated on activation normal T cell expressed and secreted (RANTES). (2) Anti-Gi inhibited their migration in response to MCP-1 or RANTES but not in response to MIP-1 alpha. Second, incubation of IANK cell membranes with anti-G protein antibodies before incubating with (gamma-35S) GTP or (gamma-32P) GTP, resulted in the following. (1) Anti-G(s), anti-G(o), or anti-G(z) inhibited GTP binding and GTPase activity in the presence of MIP-1 alpha, or RANTES. (2) Anti- G(i) inhibited GTP binding and GTPase activity in the presence of MCP-1 or RANTES but not in the presence of MIP-1 alpha. The inhibitory effect of anti-G protein antibodies was reversed upon incubating these antibodies with their respective synthetic peptides before addition to IANK cell membranes. These results suggest that MCP-1 and RANTES receptors are promiscuously coupled to multiple G proteins in IANK cell membranes and that this coupling is different from MIP-1 alpha receptors, which seem to be coupled to G(s), G(o), and G(z) but not to G(i).     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Kinetic characterization of human hydroxyacid–oxoacid transhydrogenase: Relevance toD-2-hydroxyglutaric and γ-hydroxybutyric acidurias

Summary We investigated the presence of hydroxyacid–oxoacid transhydrogenase (HOT), which catalyses the cofactor-independent conversion of γ-hydroxybutyrate (GHB) to succinic semialdehyde coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG), in human liver extracts employing [²H₆]GHB and 2-KG as substrates. We measured incorporation of ²H in D-[²H]2-HG using GC-MS analyses, providing evidence for HOT activity in humans. Kinetic characterization of HOT was undertaken in forward and reverse directions. We employed [²H₆]GHB and [²H₄]2-KG as cosubstrates in order to develop a HOT activity assay in cultured human fibroblasts derived from patients with D-2-hydroxyglutaric aciduria. HOT activity was quantified in this system by the measurement of D-[²H₅]2-HG production. Fibroblasts derived from patients with D-2-hydroxyglutaric aciduria showed normal HOT activities. Our results provide the first demonstration and preliminary kinetic characterization of HOT activity in human tissues.     

Treatment of bile duct lesions after laparoscopic cholecystectomy.

From January 1990 to June 1994, 53 patients who sustained bile duct injuries during laparoscopic cholecystectomy were treated at the Amsterdam Academic Medical Centre. There were 16 men and 37 women with a mean age of 47 years. Follow up was established in all patients for a median of 17 months. Four types of ductal injury were identified. Type A (18 patients) had leakage from cystic ducts or peripheral hepatic radicles, type B (11 patients) had major bile duct leakage, type C (nine patients) had an isolated ductal stricture, and type D (15 patients) had complete transection of the bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) established the diagnosis in all type A, B, and C lesions. In type D lesions percutaneous cholangiography was required to delineate the proximal extent of the injury. Initial treatment (until resolution of symptoms and discharge from hospital) comprised endoscopy in 36 patients and surgery in 26 patients. Endoscopic treatment was possible and successful in 16 of 18 of type A lesions, five of seven of type B lesions, and three of nine of type C lesions. Most failures resulted from inability to pass strictures or leaks at the initial endoscopy. During initial treatment additional surgery was required in seven patients. Fourteen patients underwent percutaneous or surgical drainage of bile collections, or both. After endoscopic treatment early complications occurred in three patients, with a fatal outcome in two (not related to the endoscopic therapy). During follow up six patients developed late complications. All 15 patients with complete transection and four patients with major bile duct leakage were initially treated surgically. During initial treatment additional endoscopy was required in two patients. Early complications occurred in eight patients. During follow up seven patients developed stenosis of the anastomosis or bile duct. Reconstructive surgery in the early postoperative phase was associated with more complications than elective reconstructive surgery. Most type A and B bile duct injuries after laparoscopic cholecystectomy (80%) can be treated endoscopically. In patients with more severe ductal injury (type C and D) reconstructive surgery is eventually required in 70%. Multidisciplinary approach to these lesions is advocated and algorithms for treatment are proposed.     

IgG Against Dengue Virus in Healthy Blood Donors,Zanzibar, Tanzania

We conducted a seroprevalence survey among 500 healthy adult donors at Zanzibar National Blood Transfusion Services. Dengue virus IgG seroprevalence was 50.6% and independently associated with age and urban residence. These data will aid in building a surveillance, preparedness, and response plan for dengue virus infections in the Zanzibar Archipelago.Key words: dengue, seroprevalence, Zanzibar, viruses, vector-borne infections