Sustained brain activation supporting stop-signal task performance.

Stop-signal paradigms operationalize a basic test of goal-directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop-signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop-signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop-signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop-signal task.

One phase of the dormancy developmental pathway is critical for the evolution of insect seasonality.

Evolutionary change in the timing of dormancy enables animals and plants to adapt to changing seasonal environments and can result in ecological speciation. Despite its clear biological importance, the mechanisms underlying the evolution of dormancy timing in animals remain poorly understood because of a lack of anatomical landmarks to discern which phase of dormancy an individual is experiencing. Taking advantage of the nearly universal characteristic of metabolic suppression during insect dormancy (diapause), we use patterns of respiratory metabolism to document physiological landmarks of dormancy and test which of the distinct phases of the dormancy developmental pathway contribute to a month-long shift in diapause timing between a pair of incipient moth species. Here, we show that divergence in life cycle between the earlier-emerging E-strain and the later-emerging Z-strain of European corn borer (ECB) is clearly explained by a delay in the timing of the developmental transition from the diapause maintenance phase to the termination phase. Along with recent findings indicating that life-cycle differences between ECB strains stem from allelic variation at a single sex-linked locus, our results demonstrate how dramatic shifts in animal seasonality can result from simple developmental and genetic changes. Although characterizing the multiple phases of the diapause developmental programme in other locally adapted populations and species will undoubtedly yield surprises about the nature of animal dormancy, results in the ECB moth suggest that focusing on genetic variation in the timing of the dormancy termination phase may help explain how (or whether) organisms rapidly respond to global climate change, expand their ranges after accidental or managed introductions, undergo seasonal adaptation, or evolve into distinct species through allochronic isolation.

Characteristics of research-related HIV testing programmes contribute to detection of more HIV infections.

HIV prevalence estimates from bathhouse testing programmes differ widely, ranging from 3% to 11%. The observed difference may be a consequence of whether the programme was part of a research project or a community-based programme. A research-funded testing programme was offered at a bathhouse between May 2001 and December 2002. A local community-based organization began a testing programme in July 2006 at the same bathhouse; the data for this analysis cover the period July 2006 through December 2007. County-wide HIV prevalence estimates were available across the two time periods (i.e. 2001-2002 and 2006-2007). The research-funded testing programme recruited fewer men but identified more positive individuals (10.7% of those testing in the research programme) than were identified among men who tested in the area clinics (3.8% of those men who have sex with men [MSM] testing throughout the county in the same time period). However, the community-based testing programme identified about the same proportion of positive MSM (2.6%) as county clinics (2.7%) in the same time period. In conclusion, results confirmed that even in the same venue, a community-based HIV testing programme identified a similar proportion of positive MSM as the area clinics; however, the research-funded programme identified appreciably more. Incentives may contribute to the difference.

A meta-analysis comparing side to end with colonic J-pouch formation after anterior resection for rectal cancer.

BACKGROUND: A meta-analysis of published literature comparing J-pouch with side to end anastomosis after anterior resection (AR) for rectal cancer. METHODS: Electronic databases were searched from January 1980 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Four randomized controlled trials involving 273 patients were analysed. One hundred and thirty-eight patients were in the J-pouch and 135 in the side to end anastomosis (STEA) group. No significant difference in surgically related outcomes was established (hospital stay, operative time, estimated blood loss, overall morbidity and mortality). Resting pressures at 24 months post-operatively were lower in J-pouch group compared with STEA and approached statistical significance [random effects model: SMD = -1.23, 95% CI (-2.47, -0.01), z = -1.94, P = 0.053]. No statistical difference was found in volumetric parameters (Volume at which the patient first experiences a sensation to defaecate and maximal tolerable volume). No statistical difference except urgency at 6 months [P < 0.05] was elicited in functional outcomes (use of enemas, bowel medications, pads, incomplete defaecation and stool frequency) between J-pouch and STEA groups. CONCLUSIONS: J-pouch or STEA are acceptable and safe options after AR for rectal cancer. Either approach may be considered according to surgeon choice. A randomized controlled trial including a larger number of patients is required to strengthen the evidence.

Pyrilamine in the horse: detection and pharmacokinetics of pyrilamine and its major urinary metabolite O-desmethylpyrilamine.

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 microg/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 microg/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.

Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky.

Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injured and control horses. The possible role of anti-inflammatory agents in musculoskeletal injuries of Thoroughbred race horses was investigated by comparing the apparent concentrations of NSAIDs in injured horses to concentrations in control horses. The plasma concentrations of phenylbutazone and flunixin were higher in injured horses than in control horses. Most injured and control horses did not have a detectable level of naproxen in their plasma samples. Further studies must be carried out to determine whether horses with higher plasma concentrations of NSAIDs have an altered risk of musculoskeletal injuries compared with other horses.

An isolated lump in right groin: an unusual initial presentation of Crohn's disease.

BACKGROUND: Retroperitoneal abscess, extending to the groin as an isolated tender lump, is rare as the first manifestation of Crohn's disease. CASE PRESENTATION: This report describes a young, fit and healthy 22 year-old woman with no previous history of gastrointestinal disorder, who presented with an isolated, tender lump in her right groin as the initial presentation of Crohn's disease. The patient, after a conventional incision and drainage of the abscess, was readmitted with enterocutaneous fistula at the right groin. After radiological investigations, she underwent a laparotomy, which showed jejunal perforation through ileocaecal mesentery producing retrocaecal abscess. There was also a suspicious fistulous connection between jejunum and ileo-caecal junction. A segmental small bowel resection and a limited right hemicolectomy with primary anastomoses were performed. The patient made an uneventful post-operative recovery and was discharged home on the fifth post operative day. CONCLUSION: Crohn's disease could manifest as an isolated, tender groin lump which has not been described in the published literature so far. Since retroperitoneal abscess remains a rare but serious complication of Crohn's disease, aggressive operative therapy should be ensued without delay in order to remove the source of the abscess. Groin abscess could conceal surprises and should always be investigated radiologically before proceeding to incision and drainage.

Characterization of a novel protein regulated during the critical period for song learning in the zebra finch.

A male zebra finch learns a song by listening to a tutor, but song learning is normally restricted to a critical period in juvenile development. Here we identify an RNA whose expression in the song control circuit is altered during this critical period. The RNA encodes a soluble presynaptic protein that forms a predicted amphipathic alpha helix typical of the lipid-binding domain in apolipoproteins. We show this protein, which we call synelfin, to be the homolog of the human non-A beta component (and its precursor) recently purified from Alzheimer's disease amyloid. We suggest this highly conserved protein may serve a novel function critical to the regulation of vertebrate neural plasticity.

Internet information on colorectal cancer: commercialization and lack of quality control.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of the internet as a source of information for colorectal cancer (CRC). METHOD: Six of the most common search engines (Yahoo, Google, MSN search, Alta Vista, Excite and Lycos) were used for the search of the generic term 'CRC'. First 300 links were analysed and classified by information type, provider, readership and commercial orientation. RESULTS: The average time delay was 1.70 s before matches were located. A total of 3.2827 million matches on CRC were found using the six search engines ranging from 700 (Excite) to 1 417 000 (Lycos) websites. Approximately 50% of the links were based on information from textbooks or governmental websites. Commercial companies giving information about private hospitals and products provided over 50% of the websites on CRC. The distribution of target readers was uneven, although a majority of websites were delivering CRC information to public and patients. Readability of information was difficult to comprehend by the public. CONCLUSION: The internet is becoming an essential tool for disseminating information about CRC to consumers. Half of the links on CRC are commercially oriented, containing information on goods or private health services. Less than 1% information is being provided by professional societies. To provide relevant CRC information, key consensus criteria for evaluating healthcare-related websites have to be established. There is an urgent need for CRC information on the internet to be regulated through the establishment of government-funded organizations (e.g. NHS) or professional societies (e.g. ACPGBI).

Perforated caecal volvulus: an unusual complication after anterior resection for colorectal carcinoma.

AIM: To discuss an unusual and rare complication of perforated caecal volvulus (CV) following open anterior resection. METHODS: A retrospective review of the case notes of a patient. RESULTS: CV is a well known but rare cause of bowel obstruction. Chronic constipation, distal colonic obstruction and post-operative ileus are potentially aggravating factors for the development of CV in anatomically susceptible patients. The anatomical susceptibility for CV was noticed during the first operation but prophylactic caecopexy was not performed due to lack of evidence in the literature. This patient developed CV after anterior resection and subsequently underwent a second laparotmy for right hemicolectomy. CONCLUSION: CV is a known but rare case of postoperative bowel obstruction. The role of prophylactic caecopexy could be discussed in order to avoid the development of postoperative CV in anatomically susceptible patients.

Autologous bone marrow transplantation for children with AML in first remission.

In Children's cancer group (CCG) 2891, newly diagnosed patients with AML were randomized between standard and intensive timing induction therapies. Patients in first remission who lacked an HLA matched family donor were randomized between an autologous bone marrow transplantation (ABMT) where marrow was purged with 4 hydroperoxycyclophosphamide and consolidation chemotherapy. One hundred and thirty seven patients received an ABMT. Myeloid and platelet engraftment occurred at a median of 44 and 42 days, respectively. Disease-free survival (DFS), relapse-free survival and overall survival at 8 years post induction were 47% (95% confidence interval (CI): 38-55), 50% (CI: 42-59) and 55% (CI: 46-63), respectively. Multivariate analysis of DFS showed WBC <50 000/microl and having received intensively timed induction therapy were associated with improved DFS. Recipients who received intensive timed induction therapy and whose WBC was less than 50 000/microl had a DFS at 8 years of 62% (CI: 49-73). Conversely, recipients who received intensive timed induction therapy patients whose WBC was > or =50 000/microl had a DFS of 33% (CI: 17-50), P=0.003. The results confirm previous studies that ABMT is effective post remission therapy for pediatric patients with AML in first remission.

A constitutive model for muscle properties in a soft-bodied arthropod.

In this paper, we examine the mechanical properties of muscles in a soft-bodied arthropod under both passive and stimulated conditions. In particular, we examine the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta, and show that its response is qualitatively similar to the behaviour of particle-reinforced rubber. Both materials are capable of large nonlinear elastic deformations, show a hysteretic behaviour and display stress softening during the first few cycles of repeated loading. The Manduca muscle can therefore be considered as different elastic materials during loading and unloading and is best described using the theory of pseudo-elasticity. We summarize the basic equations for transversely isotropic pseudo-elastic materials, first for general deformations and then for the appropriate uniaxial specialization. The constitutive relation proposed is in good agreement with the experimental data for both the passive and the stimulated conditions.

Long-term results of children with acute myeloid leukemia: a report of three consecutive Phase III trials by the Children's Cancer Group: CCG 251, CCG 213 and CCG 2891.

The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77-78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65+/-9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.

Postremission therapy for children with acute myeloid leukemia: the children's cancer group experience in the transplant era.

We reviewed consolidation therapy results and analyzed postremission outcomes for 1464 children less than 21 years old at diagnosis in five consecutive Children's Cancer Group acute myeloid leukemia trials between 1979 and 1996. Children in remission were allocated to allogeneic bone marrow transplantation (BMT) (N=373) in first remission, if a matched family donor was available. Remaining children were assigned consolidation chemotherapy (N=688) or autologous purged BMT (N=217), or withdrew from study before assignment, or with unknown data (N=186). Overall and disease-free survival were superior for children assigned allogeneic transplants. High (>50,000/microl) diagnostic white blood cell (WBC) count was prognostic for inferior outcome, but French-American-British (FAB) subtypes were not. Inv(16) is a favorable karyotypic feature for children in first remission and t(8;21) is not. Allogeneic transplantation benefit was evident in most children, including those with high or low diagnostic WBC count, each FAB subtype, and t(8;21), but was not seen in children with inv(16). Therefore, these data suggest reserving matched related donor allogeneic transplantation for children with inv(16) for second remission, but not those with t(8;21).

Frequency of 13q abnormalities among 203 patients with retinoblastoma.

We studied peripheral blood lymphocyte karyotypes of 203 patients with retinoblastoma. Twelve (5.9%) had a constitutional chromosomal abnormality involving 13q, of whom six had unilateral and six had bilateral disease. Two patients had mosaic deletions, eight had nonmosaic deletions, one had a de novo translocation, and one had a 13q14 deletion and a de novo direct insertion (10;6). Of the total, 4.9% of unilateral and 7.5% of bilateral patients had 13q abnormalities. None of 19 familial retinoblastoma patients had a visible cytogenetic abnormality. The unilateral patients with 13q abnormalities represent prezygotically determined (potentially heritable) cases which would have been classified as postzygotic (sporadic) without cytogenetic analysis. The observed 1% frequency of mosaic deletions is lower than that previously reported.

In vitro sensitivity of normal and hereditary retinoblastoma fibroblasts to DNA-damaging agents.

We investigated the ability of nine fibroblast cell strains from patients with the hereditary form of retinoblastoma (RB) to handle various types of DNA-damaging agents and compared the results with those obtained in nine normal strains. Cell strains were exposed to gamma-radiation, which causes DNA scission; actinomycin D, a DNA-intercalating agent; and mitomycin C, a bifunctional alkylating agent leading to DNA-DNA cross-linking. Cell strains were studied for their ability to survive in a cytotoxicity assay. Nine normal strains exhibited a mean D0 (inverse of the slope of the straight line portion of the survival curve) of 134-178 cGy after radiation exposure, compared to a range of 119-186 cGy in the nine RB strains (P = 0.33). Similarly, exposure to actinomycin D led to D0 values of 0.024-0.069 microgram/ml in the nine normal strains and D0 values of 0.016-0.067 microgram/ml in the RB strains (P = 0.64). The nine RB strains did exhibit a small overall increase in sensitivity after exposure to mitomycin C, with D0 values ranging from 0.14-0.32 microgram/ml versus 0.19-0.66 microgram/ml in the nine normal strains (P = 0.002); however, when the two most resistant normal strains were excluded from analysis, results were similar. Three RB cell strains derived from individuals who had either developed second cancers or who had a family history of additional sarcomas consistently exhibited increases in sensitivity to all three DNA-damaging agents studied compared with other hereditary RB cell strains as well as normal strains. The results suggest that normal human fibroblast cell strains exhibit a wide response to DNA-damaging agents, especially chemical agents. Most hereditary RB strains exhibit sensitivity well within the normal range; however, strains from RB patients predisposed to second cancers exhibit increases in sensitivity to DNA-damaging agents. The heterogeneous ability to repair DNA damage may play a role in the development of second malignant neoplasms in hereditarily predisposed individuals.

Immune response of BALB/c X DBA/2F1 mice to a tumor allograft during pyran copolymer-induced tumor enhancement.

The immune response of BALB/c x DBA/2 F1 mice to a transplantable Moloney leukemia virus-induced tumor allograft (MBL-2) was studied to determine the mechanism of pyran copolymer-induced tumor enhancement. The relative levels of humoral, lymphocyte, and macrophage response were followed chronologically by in vitro cytotoxic microassays using 51Cr-labeled target cells. Although pyran increased the titer of humoral cytotoxic antibody, levels of humoral factors capable of abrogating lymphocytoxicity were not enhanced. Furthermore, splenic lymphocyte-mediated cytotoxicity, although slightly diminished in pyran-treated mice, was not significantly affected. Macrophages harvested from allograft-bearing animals exhibited marked tumoricidal activity, which was augmented by pyran treatment. This macrophage-associated activity was specific for MBL-2 cells and not attributable to cytotoxins elaborated into the culture medium. Pyran slightly activated macrophages from nonsensitized mice to become cytotoxic for MBL-2 cells; activation was not T-cell dependent. However, strikingly fewer macrophages infiltrated the allograft in pyran-treated animals as judged by both histopathology and direct measurement. The defect in the migration or deposit of macrophages at the allograft site may have contributed to tumor enhancement.

Occupations of parents of children with retinoblastoma: a report from the Children's Cancer Study Group.

A matched case-control study was conducted by the Children's Cancer Study Group to investigate the role of parental occupation in the etiology of sporadic heritable and nonheritable retinoblastoma. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the Children's Cancer Study Group member hospitals. Telephone interviews of 201 parents of cases and their pair-matched controls selected by random digit dialing were completed. Of the 201 cases, 19 were familial, 67 were sporadic heritable, and 115 were nonheritable. The 19 familial cases were excluded from the analysis. Paternal employment in the military [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.1-8.8, P = 0.04] and in the metal industry (OR infinity, 95% CI 1.4-infinity, P = 0.02) was associated with sporadic heritable retinoblastoma (N = 67). For nonheritable retinoblastoma (N = 115), a significant association was observed for a job cluster consisting mostly of welders and machinists (OR 4.0, 95% CI 1.1-22.1, P = 0.04). Occupations of maternal grandparents were also studied and an association was observed with farming and nonheritable retinoblastoma (OR 10.0, 95% CI 1.4-433, P = 0.02). Many comparisons were made and the number of significant findings did not exceed that expected by chance. Thus, the results need to be interpreted very cautiously. However, the findings related to metal exposure corroborate observations on other childhood cancers.

No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.

Pre- and postconception factors associated with sporadic heritable and nonheritable retinoblastoma.

A matched case-control study of retinoblastoma was conducted by the Children's Cancer Study Group (CCSG) to investigate the hypotheses that postconception exposures affect the risk of the nonheritable (post-zygotic origin) form of this disease and that preconception exposures affect the risk of the sporadic heritable (prezygotic origin) form. Eligible cases were those patients with retinoblastoma diagnosed in 1982-1985 at any of the CCSG member hospitals. Cases were classified as familial heritable, sporadic heritable, or nonheritable based on family history, tumor laterality, and cytogenetic analysis. Telephone interviews of parents of 201 cases and their pair-matched controls selected by random digit dialing were completed. Analysis of possible risk factors for the 67 sporadic heritable cases and the 115 nonheritable cases was performed. (The 19 familial cases were excluded). For the nonheritable group, gestational exposure to X-ray [odds ratio (OR) = 2.3, P = 0.08] and morning sickness medication (OR = 2.8, P = 0.02) and low maternal educational level (OR = 5.5, P = 0.03) were associated with increased risk; anemia (OR = 0.3, P = 0.02) and multivitamin use (OR = 0.4, P = 0.03) during pregnancy and periconceptional use of barrier contraceptive (OR = 0.1, P = 0.02) or spermicide (OR = 0.2, P = 0.02) were associated with decreased risk. In the sporadic heritable group, observations included a negative association with multivitamins during pregnancy (OR = 0.2, P = 0.02) and nonsignificant positive associations with preconception gonadal X-ray (maternal, OR = 2.0, P = 0.30; paternal, OR = 1.8, P = 0.42) and older parental age (case-control difference 1.0-1.2 years, P = 0.24-0.27). Many of the associations support study hypotheses, although the possibility of recall bias and chance findings suggest cautious interpretation.