Autoimmunity, Inflammatory Bowel Disease and Hyposplenism

The presence or absence of nine autoantibodies were assessedin 44 patients with ulcerative colitis (17 with hyposplenism)and 22 patients with Crohn's disease (eight with hyposplenism).The purpose of the study was to determine whether hyposplenismin inflammatory bowel disease is associated with an increasedtendency to autoimmunity, or whether autoimmunity is linkednot to hyposplenism itself but to the underlying bowel disease.The results strongly suggest that the latter hypothesis is correct.There was a much higher frequency of autoantibodies in patientswith ulcerative colitis than in those with Crohn's disease (P0.01),suggesting that autoimmune factors are more important in thepathogenesis of ulcerative colitis than in Crohn's disease.     

Assessment of Gall Bladder Dynamics, Cholecystokinin Release and the Development of Gallstones During Octreotide Therapy for Acromegaly

The development of gallstones is a well recognized complicationof therapy with the long-acting somatostatin analogue, octreotidein patients with acromegaly. A group of nine acromegalic patientswas treated with octreotide at doses of 300–600 µgdaily for 8 months and the changes in fasting and post-prandialcholecystokinin release, and gall bladder motor function (determinedby a radiosotopic technique) were assessed at regular intervals.In addition the development of any gallstones was determinedby serial ultrasonography. Fasting cholecystokinin levels showedno significant change over 6 months, whereas the post-prandiallevels demonstrated a significant decrease (p<0.01) duringtherapy, yet remained significantly higher than fasting levels.Twenty-four hours after commencing therapy gall bladder ejectionfraction was decreased by 57±23 per cent and gall bladderejection rate decreased by 63±19 per cent compared tothe pretreatment values, whereas after 6 months, therapy a markedreduction in gall bladder ejection fraction (>35 per cent)and gall bladder ejection rate (>40 per cent) persisted inonly four of nine patients. Three of these four patients withpersistently impaired gall bladder motor function were subsequentlyshown to have developed either gallstones or biliary sludgeduring the course of therapy. We conclude that treatment with octreotide is associated withan impaired post-prandial release of cholecustokinin in allacromegalis patients, but gallstones only develop in those patientswho, in addition, have evidence of a persistently impaired gallbladder motor response to cholecyustonini.     

Impact of target-to-background ratio, target size, emission scan duration, and activity on physical figures of merit for a 3D LSO-based whole body PET/CT scanner

The aim of our work is to describe the way in which physical figures of merit such as contrast-to-noise ratio (CNR) behave when varying acquisition parameters such as emission scan duration (ESD) or activity at the start of acquisition (A(acq)) that in clinical practice can be selected by the user, or object properties such as target dimensions or target-to-background (T/B) ratio, which depend uniquely on the intrinsic characteristics of the object being imaged. Figures of merit, used to characterize image quality and quantitative accuracy for a 3D-LSO based PET/CT scanner, were studied as a function of ESD and A(acq) for different target sizes and T/B ratios using a multivariate approach in a wide range of conditions approaching the ones that can be encountered in clinical practice. An annular ring of water bags of 3 cm thickness was fitted over an IEC phantom in order to obtain counting rates similar to those found in average patients. The average scatter fraction (SF) of the modified IEC phantom was similar to the mean SF measured on patients with a similar scanner. A supplemental set of micro-hollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL, positioned on the linear portion of the phantom's NECR curve, well below peak NECR of 61.2 kcps that is reached at 31.8 kBq/mL. The ESD was set to 1, 2, 3, and 4 min/bed. With T/B ratios of 3.6, 10.3, and 22.5, the 13.0, 8.1, and 6.5 mm spheres were detectable for the whole ranges of background activity concentration and ESD, respectively. The ESD resulted as the most significant predictor of CNR variance, followed by T/B ratio and the cross sectional area of the given sphere. Only last comes A(acq) with a weight more than halved with respect to ESD. Thus, raising ESD seems to be much more effective than raising A(acq) in order to obtain higher CNR, which is the physical figure of merit closely related with target detectability, at least in the simple task of the signal known exactly background known exactly model.     

Attitudes towards mental health,mental health research and digital interventions by young adults with type 1 diabetes: A qualitative analysis

Background

Young people with type 1 diabetes are at increased risk of mental disorders. Whereas treatment need is high, difficulty recruiting young people with type 1 diabetes into psychosocial studies complicates development, testing and dissemination of these interventions.

Objective

Interviews with young adults with type 1 diabetes were conducted to examine attitudes towards mental health and mental health research, including barriers and motivators to participation in mental health studies and preferred sources of mental health support. The interviews were audio‐taped, transcribed and evaluated via thematic analysis.

Setting and participants

Young adults with type 1 diabetes were recruited via social media channels of 3 advocacy organizations. A total of 31 young adults (26 females and 5 males) with an average age of 22 years were interviewed between October 2015 and January 2016.

Results

Participants were largely unaware of their increased vulnerability to common mental health problems and knew little about mental health research. Major barriers to participation included perceived stigma and lifestyle issues and low levels of trust in researchers. Opportunities to connect with peers and help others were described as key motivators. Psychological distress was considered normal within the context of diabetes. A need for some level of human contact in receiving psychosocial support was expressed.

Discussion and conclusion

Findings provide valuable insights into the complex dynamics of engaging young adults with type 1 diabetes in mental health studies. Interviewees provided practical suggestions to assist investigation and delivery of psychosocial interventions for this vulnerable group.     

The guinea pig I region. I. A structural and genetic analysis

The Ia antigens of the guinea pig have been shown to play a central role in the regulation of the immune response. We have previously partially characterized the chemical structure of these antigens. In this communication, we further characterize the structure of the five Ia antigens already described, as well as two new Ia antigens. Evidence is presented which shows that these seven Ia antigens can be organized into three distinct groups, each with a characteristic structure. The Ia.2 determinant of strain 2 and the Ia.3 and Ia.5 determinants of strain 13 animals are found on molecules composed of a 25,000 dalton chain and a 33,000 dalton chain in noncovalent association, or else are individually expressed on nonlinked 33,000 and 25,000 dalton molecules. The Ia.4 and Ia.5 determinants of strain 2 and the Ia.7 determinant of strain 13 are borne on 58,000 dalton molecules in which two chains are linked by disulfide bonds. The Ia.1 and Ia.6 determinants of strain 13 are found on a molecule of 26,000-27,000 daltons. Ia.6 of strain 2 has yet to be definitively assigned. Furthermore, in strain 13 animals the Ia.3 and Ia.5 determinants are borne on the same molecule, as are the Ia.1 and Ia.6 determinants. In strain 2 animals, the Ia.4 and Ia.5 determinants are found on the same molecule. On the basis of chemical structure, we have divided the guinea pig I region into three subregions. The accompanying paper presents evidence of associations between particular Ia genes and Ir genes.     

A phase II study on the efficacy and safety of procedural analgesia with fentanyl buccal tablet in cancer patients for the placement of indwelling central venous access systems

Background

Pain in cancer patients is often related to oncologic therapies and diagnostic procedures. The placement of fully implantable venous access systems is a very common procedure in oncology patients. Local anaesthesia is the method most commonly used to overcome pain related to this surgical procedure, but the local anaesthetic may be unable to completely eradicate all pain. This study investigates the effectiveness and safety of fentanyl buccal tablet (FBT), administered by OraVescent® technology, in reducing procedural pain related to the placement of indwelling central venous access systems (Ports) in opioid-naïve cancer patients.

Methods

Inpatients who required an indwelling vascular access (Port) were preoperatively assessed with a self-assessment questionnaire on anxiety and pain. A 100 μg FBT was administered 10 min before preparation of the operating field. A self-assessment scale for pain experienced during the procedure was administered at the end of the procedure. Vital signs and the presence of any side effects or bothersome symptoms were monitored during the procedure, at the end, and 4 h later.

Results

From October 2012 to June 2014, 65 patients were enrolled in the study. A total of 61 (93.9 %) patients perceived no or a little pain during the procedure. Four patients (6.2 %) reported a lot of pain. No patient reported very severe pain. This data is significant in terms of the lower than expected presence of pain (Fisher test p = 0.0018) as assessed in our previous experience without procedural analgesia. The most common side effects of FBT was drowsiness, experienced by 28 patients at the end of the procedure (43.1 %), significantly reduced (p < 0.01) to 8 patients after 4 h (12.5 %). Nausea was present in 6 cases at the end of the procedure (9.2 %) and in 7 cases 4 h later (10.9 %). Vomiting was present in 3 cases at the end (4.7 %) and in 2 other patients after 4 h (7.8 %). No significant change of vital parameters was observed between the baseline and the subsequent measurements in all patients studied.

Conclusions

The significant improvement in the number of patients experiencing little or no pain, accompanied by a lower number of non-severe side effects, suggests that FBT is a valid, practical and safe method of procedural analgesia. It will be necessary to perform further studies, taking into account the need for standard antiemetic pre-medication to minimise the incidence of nausea and vomiting.