SIFT IT: A feasibility and preliminary efficacy randomized controlled trial of a social cognition group treatment programme for people with acquired brain injury.

Making sense of social situations requires social cognitive skills, which can be impaired after acquired brain injury (ABI), yet few evidence-based treatment options are available. This study aimed to evaluate the feasibility of a multi-faceted social cognition group treatment programme, SIFT IT, for people after ABI using an RCT design. Twenty-eight participants were recruited, and 23 were randomized into either Treatment or Waitlist. SIFT IT consisted of 14 weekly 90-minute small group sessions facilitated by a Clinical Psychologist. Topics included: emotion self-awareness, emotion perception, perspective taking, and choosing adaptive social responses. Preliminary efficacy outcomes were assessed at baseline, post-treatment, and three-month follow-up. Demand for treatment was evident with 61% recruitment and 91% post-treatment retention rates, with 63% attending at least 13/14 sessions. Large between-group treatment effects (with non-zero 95% confidence intervals) were observed for emotion perception, detecting hints, and informant ratings of social cognitive deficits. Implementation challenges recruiting to groups and maintaining group allocation fidelity, with a small sample size does, however, raise questions about the appropriateness of an RCT design in a future efficacy trial. Overall, this study showed there is demand for social cognitive interventions after ABI and the SIFT IT programme was practicable and acceptable to participants.Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12617000405314.

Establishing 'proof of concept' for a social cognition group treatment program (SIFT IT) after traumatic brain injury: two case studies.

OBJECTIVE: Social cognitive deficits are prevalent after traumatic brain injury (TBI). Despite this, few remediation studies exist. This study aimed to demonstrate 'proof of concept' for a novel group treatment that comprehensively targeted the core processes of social cognition. DESIGN: Pre-post case study with two participants, "Greg" and "Aaron", living with severe TBI, with three assessment time points. METHOD: Participants were screened at baseline to confirm social cognitive deficits: Greg exhibited difficulties with emotion perception and detecting hints; Aaron with detecting sarcasm and hints. Both reported everyday social problems. Participants then completed the 14-week group treatment program (SIFT IT). Feasibility and outcome measures were repeated post-group and at three-month follow-up. RESULTS: The study procedure was implemented with 100% assessment and 89% SIFT IT session attendance, albeit with a lack of proxy-report measures. Both participants described procedures as acceptable, although suggested more group participants could be beneficial. They both demonstrated reliable improvements (RCI > 1.96) on relevant social cognitive measures. Qualitative feedback corroborated findings: Greg reported generalization of therapeutic gains, Aaron reported increased self-awareness but nominal generalization. CONCLUSION: Feasibility and limited efficacy outcomes established 'proof of concept' of SIFT IT. Findings will inform the study protocol for a larger randomized-controlled trial.

High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia.

The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 +/- 18.8 vs. 9.4 +/- 3.2 mumol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.1-8.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.

[An epidemic risk of yellow fever in Burkina Faso despite a rapid immunisation riposte: role of a multidisciplinary investigation team]. / Riposte vaccinale et persistance d'un risque épidémique de fièvre jaune dans la région de Gaoua au sud-ouest du Burkina Faso: intérêt d'une équipe pluridisciplinaire.

UNLABELLED: On October 8, 1999, one yellow fever (YF) case is confirmed in the South West of Burkina Faso by the Centre Muraz' virology unit. Epidemic extension is suspected as large movements of population are occurring due to troubles in Côte d'Ivoire nearby and as the Aedes vector is endemic in the region. On October 23, the Gaoua's Health Regional Head immunizes 1,000 people around the detected YF case, i.e. 70% of the estimated population and requests an epidemiological investigation. A multidisciplinary team (epidemiologist, entomologist, virologist) from the Centre Muraz, a medical research centre based in Bobo Dioulasso investigate in order to answer the following questions: are there any other or asymptomatic cases of YF? How far is the epidemic risk? Is a paper filter a valuable method for collecting blood samples? What benefit can be gained from a multidisciplinary team? METHOD: An epidemiological analysis of the patient, a research of asymptomatic or ignored patient is performed (Health Centre registers, interview of the population). This includes the research of people missing the immunisation campaign. Blood samples are collected through 5 ml EDTA glass tubes or through filter paper in order to measure immunoglobuline M. A classical entomological prospecting completes the investigation. RESULTS: Two possible cases are suspected in the patient's home. History of the patient's is in agreement with a local contamination. In the village 110 people missed the immunisation campaign and samples were collected in 58 people including 26 children. Among them, four (15.3%) were positive with immunoglobuline M, while there were none in the adults. Aedes Luteocephalus, a potential vector is collected through night-captures but is absent of home-water collection. Paper filter assays shows a 100% concordance with classical method. CONCLUSION: The team could determine the persistency of a yellow fever epidemic risk in the region despite a rapid and adequate immunisation riposte. Due to iterative sporadic cases and due to population movement, a routine survey of YF has to be promoted as the immune status of the population, particularly in the youth, do not protect them. Collection of blood through paper filter will greatly help the routine survey and shall be confirmed during the following investigations.

Telomerase activity and cytokeratin 20 as markers for the detection and followup of transitional cell carcinoma: an unfulfilled promise.

PURPOSE: Telomerase activity compensates for the erosion of chromosomes and it has been detected in a wide variety of human tumors. Cytokeratin 20, an intermediate filament of epithelial cells, is expressed particularly in the urinary tract. These 2 molecules are candidates to become markers for the detection and followup of bladder carcinoma. We evaluate whether each molecule may serve as a potential marker and whether the 2 combined would improve the detection or followup of bladder carcinoma in a noninvasive manner. MATERIALS AND METHODS: We obtained 44 morning urine samples from patients with transitional cell carcinoma patients and 26 from age matched patients with a wide variety of clinical disorders but no malignancy of any kind. A telomerase polymerase chain reaction-enzyme-linked immunosorbent assay kit was used to determine telomerase activity and cytokeratin 20 expression was determined by nested reverse transcriptase-polymerase chain reaction. RESULTS: All samples tested positive for cytokeratin 8 expression, which verified epithelial cells in the urine samples. Of the 44 transitional cell carcinoma cases of all stages and grades 37 (84.1%) were positive for telomerase activity, 36 (81.8%) were positive for cytokeratin 20 expression and 65.9% were double positive. Of the 29 controls with various clinical conditions other that malignancy 22 (75.9%) were positive for telomerase activity, 13 (44.83%) were positive for cytokeratin 20 expression and 34.6% were double positive. CONCLUSIONS: Telomerase activity and cytokeratin 20 expression are not specific for malignancy and may be detected in many nonmalignant pathological conditions. Therefore, their use as potential markers of bladder carcinoma should be carefully reevaluated.

Urinary cytokeratin 20 as a marker for transitional cell carcinoma.

OBJECTIVES: To determine if detection of cytokeratin 20 (CK20) gene expression, by reverse transcriptase-polymerase chain reaction (RT-PCR) in urine from transitional cell carcinoma (TCC) patients, can provide a new noninvasive tool for the follow-up of patients with urothelial carcinoma of the bladder. METHODS: Urine was collected from 95 patients previously diagnosed as TCC during their follow-up, and from 27 healthy volunteers. All patients had a transurethal resection of tumor or biopsies obtained from 'suspicious' areas in the bladder. RNA was extracted from cells collected from the urine and RT-PCR was performed with specific primers for the amplification of cytokeratin 8, a general marker for epithelial cells, and of CK 20, a marker for TCC urothelium. RESULTS: CK20 expression was detected in 86.7% of TCC patients, and only in 3.3% of healthy volunteers (specificity 96.7%). Strong correlation was found between tumor grade and expression of CK20 in urine. All grade III and IV tumors demonstrated positive CK20 expression (100% sensitivity), whereas the sensitivity for lower grades was between 71 and 80%. Among 11 patients with a previous biopsy-proven diagnosis of TCC and a current negative biopsy, in 9 patients CK20 expression was detected. Further follow-up of these patients for a period of 6 months revealed recurrence of TCC in 4 patients. CONCLUSION: CK20 detection in urine cells is a simple, noninvasive method with a high potential to become the marker of choice for monitoring and follow-up of TCC patients. More information is needed regarding CK20 expression in nonmalignant urological disease, to evaluate its use for routine screening purposes.

Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy.

OBJECTIVE: Our purpose was to evaluate activated protein C resistance phenotype and genotype among patients with thrombosis during pregnancy and the puerperium. STUDY DESIGN: This observational study was conducted prospectively during a 2-year period (July 1993 to June 1995) in a preselected population. All patients admitted to our high-risk pregnancy unit with a diagnosis of deep vein thrombosis, pulmonary emboli, transient ischemic attack, and cerebrovascular accident during pregnancy and the puerperium were included. Prothrombin time, partial thromboplastin time, fibrinogen levels, protein C, protein S, antithrombin III, functional test for activated protein C resistance, and factor V Leiden mutation by polymerase chain reaction were performed on each patient. RESULTS: Fifteen patients were included. Seven (46.6%) patients were positive for activated protein C resistance (factor V Leiden). All other coagulation studies were negative for all patients. All patients with activated protein C resistance had a venous thrombotic event, deep vein thrombosis, or pulmonary emboli, and only one had a cerebrovascular accident on the basis of sagittal sinus thrombosis. Only two of the activated protein C resistance-negative patients had venous thrombosis (pulmonary emboli). The remaining six patients had transient ischemic attacks or cerebrovascular accidents. For the subgroup with venous thrombosis during pregnancy and the puerperium, the incidence of activated protein C resistance (factor V Leiden) was 78%. CONCLUSION: This study demonstrates the incidence of factor V Leiden in a selected population in whom thrombotic events developed during pregnancy and the puerperium. This small-scale study provides justification for a large cohort study that will identify women with factor V Leiden and determine their risk for thrombosis during pregnancy and the puerperium. We believe that factor V Leiden should be evaluated in conjunction with thrombotic events in the pregnant woman.

Erythropoietin-independent colonies of red blood cells and leukocytosis in a worker exposed to low levels of benzene.

BACKGROUND: Exposure to high levels of benzene commonly results in the suppression of hemopoiesis, although cases of leukocytosis and leukocytosis with thrombocytosis have been reported. No hematologic abnormalities have generally been found with exposure to low levels of benzene. METHODS: A pipe fitter exposed to low levels of benzene (time-weighted average 0.9 ppm) developed leukocytosis. His blood counts and growth of erythroid burst forming units (BFU-E) was followed with and without the addition of erythropoietin. RESULTS: Erythropoietin-independent BFU-E colonies were increased to 40 per 4 x 10(4) cells (normal < 3 per 4 x 10(4) cells). Both the leukocyte count and the number of erythropoietin-independent BFU-E colonies decreased when exposure to benzene was terminated. On reexposure the white blood count again increased. After the work was terminated, the white blood count returned to normal, as did the number of erythropoietin-independent BFU-E colonies, over a period of 12 months. CONCLUSIONS: Our findings suggest that even low levels of benzene can result in perturbations of the hemopoietic system. Further studies are warranted to determine whether these findings are idiosyncratic, coincidental, or a more general phenomenon.

Soluble factors from peripheral blood T-cells of patients with polycythemia vera stimulate normal BFU-E.

T cells and monocytes from patients with polycythemia vera (PV) were isolated and grown in culture. The conditioned medium was tested for the presence of soluble factors that promote proliferation of erythroid colonies from the blood of healthy donors. We show that T cells from all 14 PV patients that were examined secrete factor/s that stimulate the proliferation of erythroid burst-forming units (BFU-E) in the absence of an external source of erythropoietin and BPA. Addition of cyclosporin A to the culture did not inhibit the production of this activity. The conditioned medium from monocytes of PV patients can also stimulate normal BFU-E but to a much lesser extent than T-cell conditioned medium. Such stimulation was not observed with control T cells or monocytes. We observed that the fraction of DR-positive T cells was significantly higher in PV patients comparing to normal. These results suggest that PV patients possess an abnormally high level of circulating activated T cells which may in turn be the source of the putative factor that facilitates uncontrolled erythroid differentiation.

Retroviral-mediated gene transfer into CD34-enriched human peripheral blood stem cells.

Retroviral-mediated gene transfer has been shown to be a feasible method for the introduction of new genes into bone marrow hematopoietic stem cells. We have investigated the application of this technology to primitive CD34-enriched human peripheral blood cells as a potential alternative stem cell source. Bone marrow (BM) and peripheral blood (PB) CD34-enriched cells from normal volunteers and patients with multiple myeloma were exposed to retroviral vectors containing the neomycin-resistance gene and gene transfer efficiency into colony-forming unit colonies (CFU-C) and CD34+ cells was assessed by polymerase chain reaction (PCR). Peripheral blood was a target equally efficient to BM, and PB cells mobilized with chemotherapy and growth factors were also shown to take up retroviral vectors readily. Conditions favoring gene transfer were investigated, and exposure of cells to interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor (SCF) during a 72-hour transduction was found to be most effective. The use of PB stem cells as targets for gene transfer could allow repeated collections and transductions, with obvious advantages over a single BM collection.

Evidence for the existence of circulating monoclonal B-lymphocytes in multiple myeloma patients.

Multiple myeloma is characterized by the proliferation of a single clone of plasma cells producing a homogeneous immunoglobulin fraction. In this disease, plasma cells home essentially in the bone marrow. However, controversy exists whether peripheral blood B-lymphocytes in patients with multiple myeloma (MM) are part of the malignant clone. We investigated clonal immunoglobulin gene rearrangement (IgGR) in T-cell-depleted peripheral blood mononuclear cells as well as in bone marrow of these patients. Seven out of 17 MM patients demonstrated an identical IgGR in bone marrow and peripheral mononuclear cells, these patients were in an active stage of the disease. In nine patients in plateau phase, clonal IgGR could not be detected in peripheral blood. Peripheral mononuclear cells from ten patients with monoclonal gammopathies of undetermined significance (MGUS) were also examined and no IgGR was detected. The existence of monoclonal B-lymphocytes in the circulation of patients with MM suggests a mechanism whereby the malignant clone homes in the bone marrow through peripheral blood. These findings may also be used for the evaluation of patients with active myeloma and the determination of plateau phase.

Effect of adherent cells on the regulation of BFU-E in patients with myeloproliferative disease.

The interaction between adherent cells and red cell progenitors from peripheral blood of patients with polycythemia vera (PV), essential thrombocytosis (ET), and healthy controls was studied. Various combinations of adherent and nonadherent cells were co-cultured in a semisolid system. Adherent cells from controls, when added at low concentrations, stimulated BFU-E proliferation, whereas high concentrations (40% of total cells in the culture) caused a significant decrease in the number of BFU-E colonies in 6/8 PV patients, 4/4 ET patients, and 8/12 controls. On the other hand, low and high concentrations of adherent cells from both patients with PV and ET caused a significant increase in BFU-E from either patients or controls. Moreover, adherent cells from these patients induced endogenous BFU-E proliferation (independent of erythropoietin) in nonadherent cells of 12/12 normal controls. The results show that BFU-E from patients with PV and ET are sensitive to suppression by normal adherent cells. On the other hand, adherent cells from these patients possess stimulatory activity on BFU-E from peripheral blood at all concentrations and are devoid of the inhibitory activity. This suggests a possible defect in the functioning of adherent cells in PV and ET patients which may contribute to the abnormal regulation of hematopoiesis in these disorders.

Prospective longitudinal study of rotavirus infections in children from birth to two years of age in Central Africa.

A cohort of 111 children born in Bangui (Central African Republic) was followed from birth to two years of age for rotavirus infections by biweekly stool investigations until six months of age, as well as at each diarrhoeic episode. Thirty-eight children (34.2%) exhibited at least one rotavirus infection by the age of 6 months. Thirty children (27%) presented with rotavirus-associated diarrhoea before 2 years of age. Until the children reached the age of 12 months, rotavirus was identified significantly more frequently in diarrhoeic stools than in non-diarrhoeic stools (p less than 0.001). A low diversity of characterized rotavirus strains was found; only two electrophoretypes were identified, and 91% of the strains belonged to subgroup II, serotype 1, with no special strain identified in newborns. A total of 38 children had a rotavirus infection before the age of six months, while 73 did not: only 2.6% of the first group had diarrhoea associated with rotavirus between 6 and 24 months, versus 20.5% in the second group (p less than 0.05). In two-thirds of the cases of infection, the presence of rotavirus in stools was detected only once; repetitive isolations were more frequent in diarrhoeic than in asymptomatic infections. The isolation rate of rotavirus in the general populations was found to be very low (0.2%).

Prospective study of enteric Campylobacter infections in children from birth to 6 months in the Central African Republic.

A survey of enteric Campylobacter infections was performed in Bangui, Central African Republic, with a cohort of 127 children from birth to 6 months of age by biweekly culture of stools; 82 infections were observed, and 41.7% of the children presented at least 1 infection before 6 months of age. Only 15.9% of the infected children had a diarrheic syndrome; moreover, 61.5% of these diarrheic children had another enteropathogen associated with Campylobacter species. In about half the cases, Campylobacter spp. were excreted for more than 4 days. More than half of the children had at least one diarrheic episode, for which an enteropathogen was identified in one third of the cases, before 6 months of age.

PIP: Prospective surveillance of enteric Campylobacter infection from birth to 6 months of age was carried out in a cohort of infants delivered in a maternity ward in the Central African Republic city of Bangui. The purpose of the study was to define the factors explaining the existence of a large number of healthy carriers of enteric Campylobacter species in this region. 82 infections were observed in the cohort of 127 infants; 42% of the children presented with at least 1 infection before 6 months of age. Only 16% of the infected children had a diarrheic syndrome; moreover, 62% of these diarrheic children had another enteropathogen associated with Campylobacter infection. The median duration of prolonged elimination of the Campylobacter germ was 7-8 days in both asymptomatic and diarrheic infants. Isolation rates of Campylobacter were highest among children who were exclusively breastfed. 4 infants were infected with Campylobacter by the 3rd day of life and 11 were infected by 1 month of age. The number of observed infections was significantly higher in the 3-6 month age group than between 4-6 months of age. The early age and frequency of contact of children with Campylobacter species may explain the large number of healthy carriers observed among children 6-24 months of age in a previous etiologic investigation.

pHG165: a pBR322 copy number derivative of pUC8 for cloning and expression.

During the construction of the Messing pUC plasmid series, the rop(rom) gene of pBR322 which mediates the activity of RNAI was deleted. This has resulted in an elevated copy number for the pUC plasmids which makes the expression of beta-galactosidase activity constitutive in a host containing the Iqtss lac repressor. We describe the construction of a new series of vectors which retain the pUC multiple cloning site (MCS) but in which copy number control has been recovered. In addition, the lac alpha/lac promoter expression region has been inserted into a HpaI cassette. This facilitates the movement of recombinant DNA clones within the MCS. It also increases the complementation activity of the lac alpha peptide by an order of magnitude, allowing selection of recombinants by their Lac- phenotype on MacConkey agar.

Specific DNA sequences associated with the nuclear matrix in synchronized mouse 3T3 cells.

Eukaryotic chromatin appears to be organized into arrays of supercoiled loops anchored to the scaffolding structure of the mitotic chromosome core or to the nuclear matrix of interphase nuclei. To reveal whether specific DNA sequences are involved in this level of chromatin organization, we isolated and cloned a population of DNA molecules [average length of 150 base pairs (bp)] closely associated with the nuclear matrix after exhaustive DNase digestion and subsequent extensive protease digestion. The nuclear matrix was obtained from murine BALB/c 3T3 cells synchronized at the G1/S border of the cell cycle. We report the structure of two sequences, designated G4 and G5, which are highly enriched in the matrix DNA. Sequence G4, of 152 bp, contains three 31-bp direct head-to-tail repeats. An 11-bp sequence at the end of each repeat is homologous to the first large tumor antigen recognition site of human papova virus. Sequence G5, of 135 bp, consists of two well-defined domains, in which the first domain is a fragment of the B1 repetitive sequence. The results suggest the possibility that the loops of histone-depleted chromatin are connected to the scaffold of the nuclear matrix, with specific DNA sequences at the anchorage sites.