Circulating Pancreatic Polypeptide in Patients with Adenocarcinoma of the Bile Duct

Using radioimmunoassay methods, the blood of patients with pancreatic tumors was screened for circulating polypeptide hormones. This screening discovered pancreatic polypeptide in abnormally high concentration in the serum of six of seven patients with adenocarcinomas of the bile duct. the assay appears to be very sensitive finding excessive residual pancreatic polypeptide production after palliative resections. Serum pancreatic polypeptide assays warrant evaluation as an aid in the diagnosis and management of patients with bile duct tumors.     

Finding a place for needle exchange programs

Using the concepts of stigma, NIMBY and place, this paper examines the difficulties of finding a place for needle exchange programs (NEPs). Data were drawn from semi-structured interviews with NEP staff (Ontario, Canada) that focused on operational policies and routines. An iterative, inductive analytic process was used. NEPs, their staff and clients are not always welcome additions to organizations or communities because of concerns about the ‘dangerousness’ of clients and the potential contamination of communities and workplaces by stigmatized individuals and their artefacts (e.g. contaminated injection equipment). Public parks where a lot of drug ‘action’ takes place are good destinations for outreach workers but these places are contentious sites for NEP activities, particularly when residents do not perceive a need for the program and/or want to redefine their neighbourhoods. Issues of ‘place’ are further complicated when service delivery is mobile. Finding a place within organizations is difficult for NEPs because of concerns about the diversion of limited financial and spatial resources to ‘non-core’ activities and ‘undesirable’ clients. Workers respond to these challenges by contesting the social and spatial boundaries of who is an acceptable client or neighbour and refuting the perceived ‘differentness’ of injection drug users. Implementation of an unpopular service involves a delicate balancing act of interests, understanding of the dynamics of particular communities and a willingness to reinvent and redefine programs. The sociospatial stigmatization of injection drug use has had a negative impact on NEPs, and perhaps limits HIV prevention efforts.     

The hereditary spectrum of pancreatic cancer: the Edmonton experience.

OBJECTIVE: Pancreatic cancer is known to aggregate in some families and has been associated with a wide variety of cancer syndromes. The authors describe their experience with pancreatic cancer and the range of associated cancer syndromes. METHODS: The charts of all patients seen for concern of a hereditary cancer syndrome in the Cancer Genetics Clinic at the University of Alberta between 1995 and 2002 were reviewed. RESULTS: Forty families reported a personal or family history of pancreatic cancer in the context of a possible hereditary cancer syndrome. Three additional families reported a history of pancreatitis. Twenty-four (56%) of those families were suspected of having a hereditary breast and ovarian cancer syndrome. A further seven (16%) were suspected of having hereditary nonpolyposis colon cancer. Only three (7%) were believed to be at risk for a site-specific pancreatic cancer syndrome. Another three (7%) were suspicious for hereditary pancreatitis. The remaining family histories were suggestive of Li-Fraumeni syndrome, von Hippel-Lindau syndrome or a nonspecific cancer predisposition. CONCLUSIONS: With such a wide variety of hereditary cancer syndromes associated with pancreatic cancer, an accurate assessment of the family history is essential to determine the most appropriate cancer screening for at-risk family members and to guide any molecular testing that may be offered.     

Resilience in Families with Children and Adult Members with Intellectual Disabilities: Tracing Elements of A Psycho‐Social Model

Aim This paper seeks to illumine how families with children and adult members with intellectual disabilities manage to manifest a buoyant and durable capacity over time. It is therefore concerned centrally with the idea of resilience. Method Drawing from diverse theoretical literatures from child development and protection and gerontology, the paper begins with a review of constructions of resilience. In an attempt to assess where there seems to be support for resilience in families, the core of the paper tests empirical evidence about positive experiences of families supporting children and adults with intellectual disabilities against the theoretical literature on resilience. Result and Conclusions The findings are used to suggest conditions under which resilience is produced and maintained, and to identify emergent elements of a psycho‐social model of resilience in families with children and adult members with intellectual disabilities.     

Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility

Development of a disease screening biomarker involves several phases. In phase 2 its sensitivity and specificity is compared with established thresholds for minimally acceptable performance. Since we anticipate that most candidate markers will not prove to be useful and availability of specimens and funding is limited, early termination of a study is appropriate, if accumulating data indicate that the marker is inadequate. Yet, for markers that complete phase 2, we seek estimates of sensitivity and specificity to proceed with the design of subsequent phase 3 studies. We suggest early stopping criteria and estimation procedures that adjust for bias caused by the early termination option. An important aspect of our approach is to focus on properties of estimates conditional on reaching full study enrollment. We propose the conditional‐UMVUE and contrast it with other estimates, including naïve estimators, the well‐studied unconditional‐UMVUE and the mean and median Whitehead‐adjusted estimators. The conditional‐UMVUE appears to be a very good choice. Copyright © 2008 John Wiley & Sons, Ltd.     

Work disability in adults with cystic fibrosis and its relationship to quality of life.

With increasing numbers of cystic fibrosis (CF) patients surviving to adulthood, issues related to vocation inevitably arise and warrant specific attention. We examined the percentage of participants with CF currently working and explored risk factors for work disability among adults with CF. METHOD: We recruited 50 consecutive patients from an adult cystic fibrosis service. Demographic, employment history, illness severity indicators and CF-attributed work disability factors were evaluated. Demographic risk factors for work disability using the illness severity measures of FEV(1), S-K score, CRDQ, and recent hospitalisation as independent variables were determined. RESULTS: Factorial analysis of a disability index (DI) indicated no dependency on FEV(1) or S-K score, but dependency on quality of life indices (p<0.05), age (p<0.05) and hospital admission rate (p<0.05). Hours worked per week were dependent on quality of life (p<0.01) (mastery of disease domain), fewer hospital admissions (p<0.01) and age (p<0.05). Sixty-eight percent of the sample reported that CF resulted in significant impediments to employment. However, few had sought vocational guidance (6%). CONCLUSION: Determinants of workforce participation shows that hours worked and perceived disability are more dependent on mastery of disease, age, and time in hospital, than on clinical severity scores. Health professionals may assist productivity through career counselling or tailored programs.     

Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial.

OBJECTIVE: This pilot study's aim was to establish feasibility of a protocol for delayed cord clamping (DCC) versus immediate cord clamping (ICC) at preterm birth and to examine its effects on initial blood pressure and other outcomes. STUDY DESIGN: A randomized controlled trial recruited 32 infants between 24 and 32 weeks. Immediately before delivery, mothers were randomized to ICC (cord clamped at 5 to 10 seconds) or DCC (30- to 45-second delay in cord clamping) groups. RESULTS: Intention-to-treat analyses revealed that the DCC group were more likely to have higher initial mean blood pressures (adjusted OR 3.4) and less likely to be discharged on oxygen (adjusted OR 8.6). DCC group infants had higher initial glucose levels (ICC=36 mg/dl, DCC=73.1 mg/dl; p=0.02). CONCLUSION: The research design is feasible. The immediate benefit of improved blood pressure was confirmed and other findings deserve consideration for further study.     

CNS 7056: A Novel Ultra-short-acting Benzodiazepine

Background: A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo.

Methods: The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes ([alpha]1[beta]2[gamma]2, [alpha]2[beta]2[gamma]2, [alpha]3[beta]2[gamma]2, [alpha]5[beta]2[gamma]2) of the [gamma]-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test.

Results: CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 [mu]m) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil.