Ureteral length in live donor kidney transplantation; Does size matter?

The aim of this study was to evaluate the role of ureteral length on urological complications. Data were retrospective collected from the INEX‐trial database, a RCT to compare the intravesical to the extravesical ureteroneocystostomy. Ureteral length was measured in 198 recipients and used to divide recipients into three categories based on interquartile ranges: short (≤8.5 cm), medium (8.6–10.9 cm) and long ureters (≥11 cm). Urological complications were defined as the number of percutaneous nephrostomy placements (PCN). Fifty recipients fell into the short, 98 into the medium and 50 recipients into the long ureter category. Median follow‐up was 26 (range 2–45) months. There was no significant difference in number of PCN placements between the categories. There were 9 (18%) PCN placements in the short ureter category, 21 (20%) in medium ureter category and 10 (21%) in the long ureter category, P = 0.886. Risk factor analysis for gender, arterial multiplicity and type of ureteroneocystostomy showed no differences in PCN placements between the three ureteral length categories. We conclude that ureteral length alone does not seem to influence the number of urological complications.     

Physical function and fitness in long-term survivors of childhood leukaemia

Objective: To evaluate the physical function and fitness in survivors of childhood leukaemia 5–6 years after cessation of chemotherapy.

Materials and methods: Thirteen children (six boys and seven girls; mean age 15.5 years) who were treated for leukaemia were studied 5–6 years after cessation of therapy. Physical function and fitness were determined by anthropometry, motor performance, muscle strength, anaerobic and aerobic exercise capacity.

Results: On motor performance, seven of the 13 patients showed significant problems in the hand-eye co-ordination domain. Muscle strength only showed a significantly lower value in the mean strength of the knee extensors. The aerobic and the anaerobic capacity were both significantly reduced compared to reference values.

Conclusion: Even 5–6 years after cessation of childhood leukaemia treatment, there are still clear late effects on motor performance and physical fitness. Chemotherapy-induced neuropathy and muscle atrophies are probably the prominent cause for these reduced test results. Physical training might be indicated for patients surviving leukaemia to improve fitness levels and muscle strength.     

Long-term outcome of kidney transplantation in patients with a urinary conduit: a case–control study

Purpose

To study the short- and long-term outcomes of kidney transplantation in patients with a bladder augmentation or urinary diversion compared to patients with a kidney transplantation in a normal functional bladder.

Patients and methods

Between January 2000 and March 2011, 13 patients received 16 grafts into a reconstructed urinary tract. We performed a retrospective case–control study and matched each patient to 4 controls for donor and recipient gender and year of transplantation.

Results

Short- and long-term complications of kidney transplantation occurred in 12 patients, varying from urinary tract infections to medical hospitalization with or without surgical or radiological intervention. In 5 patients, a percutaneous nephrostomy (PCN) was placed followed by surgical re-intervention. In three patients, the grafts failed as a result of chronic rejection and were re-transplanted. There was no graft loss as a result of surgical complications or the reconstructed urinary tract. One-year patient and graft survival was 100 %. After five years, all patients were alive and seven of nine grafts (77.8 %) were functioning. Mean follow-up time was 4.3 years. Among the controls, 55 grafts were transplanted in 52 patients. Ten patients received a PCN. Five patients needed surgical re-intervention. In three patients, transplantectomy was performed for ongoing rejection. Three patients were re-transplanted. One patient had a failing graft 7.5 years post-transplantation and became dialysis dependent.

Conclusion

Kidney transplantation in patients with a reconstructed urinary tract has an increased complication rate. Nevertheless, the long-term results are comparable to patients with a normal urinary bladder.     

Stress-reactivity in psychosis: evidence for an affective pathway to psychosis

This paper will review a series of studies using the Experience Sampling Method that suggest that altered sensitivity to stress is an endophenotype for psychosis. The Experience Sampling Method is a structured diary technique allowing the assessment of emotional reactivity to stressors occurring in normal daily life. Elevated emotional reactivity to stress was found in subjects vulnerable to psychosis, suggesting that affective responses to stressors in the flow of daily life are an indicator of genetic and/or environmental liability to psychosis. Indeed, the small stressors in daily life associated with affective responses also predict more intense moment-to-moment variation of subtle positive psychotic experiences. Increased emotional reactivity was found to be independent from cognitive impairments, and argued to constitute evidence of an affective pathway to psychosis that may underlie a more episodic, reactive, good-outcome type of psychosis. Evidence for this hypothesis was found in data suggesting that the experience of stressful life events and early trauma were associated with increased stress-sensitivity, and that women were more likely to display elevated stress-reactivity. These findings are discussed in the light of recent biological and psychological mechanisms.     

Striatal dopamine release and impaired reinforcement learning in adults with 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk for developing psychosis. The catechol-O-methyltransferase (COMT) gene is located in the deleted region and involved in dopamine (DA) breakdown. Impaired reinforcement learning (RL) is a recurrent feature in psychosis and thought to be related to abnormal striatal DA function. This study aims to examine RL and the potential association with striatal DA-ergic neuromodulation in 22q11DS. Twelve non-psychotic adults with 22q11DS and 16 healthy controls (HC) were included. A dopamine D_2/3 receptor [¹⁸F]fallypride positron emission tomography (PET) scan was acquired while participants performed a modified version of the probabilistic stimulus selection task. RL-task performance was significantly worse in 22q11DS compared to HC. There were no group difference in striatal nondisplaceable binding potential (BP_ND) and task-induced DA release. In HC, striatal task-induced DA release was positively associated with task performance, but no such relation was found in 22q11DS subjects. Moreover, higher caudate nucleus task-induced DA release was found in COMT Met hemizygotes relative to Val hemizygotes. This study is the first to show impairments in RL in 22q11DS. It suggests that potentially motivational impairments are not only present in psychosis, but also in this genetic high risk group. These deficits may be underlain by abnormal striatal task-induced DA release, perhaps as a consequence of COMT haplo-insufficiency.     

Time-Lagged Moment-to-Moment Interplay Between Negative Affect and Paranoia: New Insights in the Affective Pathway to Psychosis

Evidence suggests that affect plays a role in the development of psychosis but the underlying mechanism requires further investigation. This study examines the moment-to-moment dynamics between negative affect (NA) and paranoia prospectively in daily life. A female general population sample (n = 515) participated in an experience sampling study. Time-lagged analyses between increases in momentary NA and subsequent momentary paranoia were examined. The impact of childhood adversity, stress sensitivity (impact of momentary stress on momentary NA), and depressive symptoms on these time-lagged associations, as well as associations with follow-up self-reported psychotic symptoms (Community Assessment of Psychic Experiences and the Symptom Checklist-90-Revised) were investigated. Moments of NA increase resulted in a significant increase in paranoia over 180 subsequent minutes. Both stress sensitivity and depressive symptoms impacted on the transfer of NA to paranoia. Stress sensitivity moderated the level of increase in paranoia during the initial NA increase, while depressive symptoms increased persistence of paranoid feelings from moment to moment. Momentary paranoia responses to NA increases were associated with follow-up psychotic symptoms. Examination of microlevel momentary experience may thus yield new insights into the mechanism underlying co-occurrence of altered mood states and psychosis. Knowledge of the underlying mechanism is required in order to determine source and place where remediation should occur.Key words: momentary assessment methodology, stress, childhood adversity, psychotic symptoms, depressive symptoms     

Familial Liability to Psychosis Is Associated With Attenuated Dopamine Stress Signaling in Ventromedial Prefrontal Cortex

Objective: Patients diagnosed with a psychotic disorder and their first-degree relatives display increased reactivity to stress. Theory predicts that experience of psychosocial stress is associated both with ventromedial prefrontal and mesolimbic dopamine neurotransmission. However, while there is evidence of aberrant striatal dopamine processing in psychotic disorder, the role of the prefrontal cortex remains under-researched. This study aimed at investigating stress-induced in vivo dopamine release in ventromedial prefrontal cortex (vmPFC) of individuals at familial risk for psychosis. Method: Fourteen healthy first-degree relatives of patients with a diagnosis of psychotic disorder and 10 control subjects underwent a single dynamic positron emission tomography (PET) scanning session after intravenous administration of 183.2 (SD = 7.6) MBq [¹⁸F]fallypride. Psychosocial stress was initiated at 100min postinjection using a computerized mental arithmetic task with social evaluative threat components. PET data were analyzed using the linearized simplified reference region model. Regression analyses were performed to compare the spatial extent of task-related ligand displacement between control subjects and relatives and to find how it related to self-rated experiences of psychosocial stress and psychosis. Results: First-degree relatives displayed hyporeactive dopamine signaling in the vmPFC in response to stress. Increased levels of subjectively rated stress were associated with increased intensity of psychotic experiences. This effect was particularly pronounced in first-degree relatives. Conclusion: Although previous studies have hypothesized a role for prefrontal dopamine dysfunction in psychosis, this study, to our knowledge, is the first in vivo human imaging study showing attenuated (ie, hyporeactive) dopamine stress neuromodulation in vmPFC of individuals at familial risk for psychosis.Key words: schizophrenia, positron emission tomography, neuromodulation, relatives, mesolimbic, salience     

A photo-CIDNP study of the interaction of oligonucleotides with gene-5 protein of bacteriophage M13.

It is shown that photo-CIDNP effects (CIDNP, chemically induced dynamic nuclear polarization) can be generated in the 360-MHz proton NMR spectrum of gene-5 protein from bacteriophage M13. This technique is used to determine the number of tyrosyl residues at the surface of the protein and to assign the resonances from the 3,5-ring protons of these residues. The DNA-binding site of the protein is investigated by formation of complexes with oligonucleotides. Complex formation leads to shifting and/or quenching of the photo-CIDNP emission signals of the surface tyrosines, implying that they are involved in DNA-protein interaction. These experiments are complemented by studying the complex formation of Lys-Tyr-Lys to poly(A).