URETERAL TISSUE EXPANSION FOR BLADDER AUGMENTATION

Purpose

Ureteral augmentation is an effective method of bladder reconstruction using the native urothelium of a megaureter. Clinically this procedure is contingent on the presence of an enlarged ureter. We have iatrogenically produced a segmental megaureter, while preserving renal function in a pig model. The urothelium of the enlarged ureter was then used for augmentation cystoplasty.

Materials and Methods

A tissue expander suitable for insertion into the lumen of the ureter was constructed. The tissue expander was passed antegrade through a flank incision of 8 pigs, and a separate nephrostomy tube was left in place. During the ensuing 1 to 4 weeks the pigs underwent daily dilation of the tissue expander without anesthesia. After dilation the pigs underwent ureteral augmentation of the bladder. The segment of expanded ureter was isolated from the native ureter, opened and anastomosed to the bladder. The continuity of the left ureter was restored by primary ureteroureterostomy. The animals underwent cystograms at 1 and 4 weeks and were sacrificed 4 weeks after augmentation. Tissue was harvested for gross and microscopic histology.

Results

Of the 8 pigs starting the protocol 5 underwent successful ureteral tissue expansion followed by bladder augmentation. Tissue expansion was performed from 1 to 4 weeks, and volumes of 150 to 1,000 cc were obtained. Two to 3 weeks of dilation was optimal to achieve ease of dilation, and no animal showed evidence of discomfort or failure to thrive. All 5 animals underwent successful ureteral augmentation with primary ureteroureterostomy. Tissue expansion volumes of approximately 250 cc were optimal for tissue management and ease of augmentation. Cystograms of all augmented animals showed increased bladder capacity with filling of the ureteral segment. Histological examination of the ureteral augmentation revealed preservation and regeneration of the urothelial mucosa.

Conclusions

The use of a tissue expander in the lumen of the ureter is a novel method of generating urothelium for use in bladder augmentation. It may provide an alternative to bowel in patients who require bladder augmentation. Long-term studies are currently under way.     

D2 DOPAMINE RECEPTOR TaqI ALLELES IN MEDICALLY ILL ALCOHOLIC AND NONALCOHOLIC PATIENTS

The prevalence of TaqI A alleles of the D₂ dopamine receptor(DRD2) gene was examined in two subgroups of medically ill nonalcoholics(more prevalent and less prevalent substance users, MPSU andLPSU, respectively) and in two subgroups of medically ill alcoholics(more severe and less severe alcoholics, MSA and LSA, respectively).The prevalence of the Al allele in the 80 nonalcoholic and 73alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009).In the four subgroups of these patients, the prevalence of thisallele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA= 58.3%. Linear trend analysis showed that as the use of substancesand severity of alcoholism increase, so does Al prevalence (P= 0.001). Specific, subgroup comparisons showed Al prevalencein MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04)higher than in LPSU and MPSU subgroups, respectively. Similarly,in a combined analysis of independent studies, Al prevalencein MSA was higher when compared to LSA (P < 5 x 10^–3),MPSU (P < l0^–4 and LPSU (P < l0^–8) subgroups.There was virtually no difference in the prevalence of the Alallele between LSA and MPSU subgroups. None of the specificmedical or neuropsychiatric complications of alcoholism wasassociated with the Al allele. In conclusion, the severity ofalcohol dependence in alcoholics and of substance use behaviorsin controls are important variables in DRD2 allelic association.The present report and converging lines of evidence suggestthat the DRD2 locus could represent a prominent gene risk factorfor susceptibility to severe alcoholism. However, other genesand environmental factors, when combined, still play the largerrole.     

Prepulse inhibition decreases as startle reactivity habituates

In the present study, I investigated the effect of stimulus repetition on human startle eyeblink reflex inhibition (PPI) by a prepulse. Participants were assigned to one of three groups (n= 14 each). in which they received 18 trials of (a) noise startle stimuli presented alone or preceded by 1000-Hz tone prepulses, (b) startle stimuli presented alone, or (c) prepulses presented alone. All participants then received 18 more trials of startle stimuli presented alone or preceded by 1000-Hz tone prepulses, followed by 6 trials of startle stimuli presented alone or preceded by 2000-Hz tone prepulses. As trials progressed, startle eyeblink electromyogram magnitude habituated and PPI decreased. PPI was not affected by the repeated presentation of the prepulses alone but decreased with the repeated presentation of the startle stimulus alone. Changes in the frequency of the prepulse had no significant effect on PPI. These data suggest that the reduction of PPI that is seen across trials is not due to habituation of the prepulse but is related to startle reactivity in control trials, which is reduced by habituation.     

Acrobeads Test as a Predictor of Fertilization In Vitro

PROBLEM: To determine whether the results of the Acrobeads test, which measures the expression of the complement regulator molecule CD46 on the inner acrosomal membrane following the acrosome reaction, accurately identifies semen specimens that will exhibit reduced or failed fertilization following conventional IVF insemination. METHOD: The Acrobeads test was performed on semen specimens from 97 consecutive patients preparing to undergo an PVF cycle utilizing a standardized insemination protocol. Motile sperm populations were examined at 6 h and 24 h post-isolation for sperm-bead agglutination. Results of the Acrobeads test were compared to that of TRITC-PSA staining in matched specimens to directly measure the spontaneous loss of acrosome content. The percentages of TRITC-PSA-negative sperm were determined in freshly isolated motile populations and in duplicate aliquots incubated 18 to 20 h under sperm capacitating conditions. The relationship between the results of both analyses estimating spontaneous acrosome reactions and the rate of fertilization of metaphase II oocytes was examined. RESULTS: The Acrobeads score did not correlate significantly with the rate of fertilization by insemination at 6 h or at 24 h. The negative predictive value of this test was 21.4%. There was no correlation between the Acrobeads score and the percentage of sperm undergoing a spontaneous acrosome reaction as detected by TRITC-PSA labeling. In contrast, the increment increase in the percentage of spontaneous acrosome reactions as quantified by TRITC-PSA staining was correlated with the fertilization rate. CONCLUSIONS: Contrary to previous reports, our prospective, double-blinded study failed to demonstrate that the Acrobeads test can accurately predict fertilization outcome in IVF. Therefore, the routine use of this test to screen patients prior to an IVF cycle in order to select appropriate treatment (i.e., ICSI) cannot be recommended.     

POST-INTENSIVE CARE SYNDROME FOLLOWING CARDIOTHORACIC CRITICAL CARE: FEASIBILITY OF A COMPLEX INTERVENTION

ObjectivesTo describe the long-term outcomes of cardiac intensive care unit patients and their primary caregivers, and to explore the feasibility of implementing a complex intervention, designed to support problems associated with post-intensive care syndrome and post-intensive care syndrome– family, in the year following discharge from the cardiac intensive care unit.DesignA complex multidisciplinary rehabilitation programme, delivered as a quality improvement initiative, in a single centre in the West of Scotland. Outcomes were measured using surveys of health related quality of life, self efficacy, anxiety, depression, pain, caregiver strain, and insomnia.ParticipantsPatients and their caregivers were invited to participate 12 weeks after hospital discharge. Twenty-seven patients and 23 caregivers attended the programme.ResultsOver 90% of patients had problems in at least one quality of life domain at baseline, 41% of patients had symptoms of anxiety and 22% had symptoms of depression. During the baseline visit, caregiver strain was present in 20% of caregivers, 57% had symptoms of anxiety, and 35% had symptoms of depression. Improvements in outcomes were seen in both patients and caregivers at 1-year follow-up. The programme was implemented, and iterative learning obtained about the content and the operationalization of the service, in order to understand feasibility.ConclusionThis small-scale quality improvement project has demonstrated that this complex multidisciplinary rehabilitation programme is feasible and has positive implications for patients following discharge from the cardiac intensive care unit, and their caregivers.LAY ABSTRACTPatients, and relatives (or caregivers) of patients, treated in specialist intensive care units often only have access to limited recovery programmes focussing on a single disease. For patients treated in general intensive care units a recovery programme called InS:PIRE has been developed. The programme runs over multiple weeks, combining healthcare teams with social and financial help, and involves community organizations. It also brings groups of patients and relatives together so that they can help each other (known as peer support). This study describes the process of adapting the InS:PIRE programme for those treated in a specialist heart and lung centre. The problems these patients and relatives experience in the year after their illness is described, demonstrating that these issues are similar to those experienced after general intensive care. The results show that this model of recovery is possible in this setting and appears to be valued by the participating patients and relatives.Key words: rehabilitation, post-intensive care syndrome, cardiac, quality improvement

Most patients now survive major cardiac surgery, and survival after cardiac arrest is also increasing (1). The American Heart Association has highlighted that such survivorship can be associated with long-lasting emotional, cognitive, physical, and social problems (2).Post-intensive care syndrome (PICS) and post-intensive care syndrome–family (PICS-F) are well recognized following general intensive care unit (ICU) care (3). PICS appears to encompass the same spectrum of problems (social, physical, cognitive, and emotional), with similar timelines for partial or complete recovery to those in patients after cardiac events (2, 3). These parallel recovery trajectories are also comparable for family members (4). One of the few documented differences in recovery trajectories, however, may be a more stark dichotomization in the cardiac population. Some patients follow a clear linear improvement over the first year, while others plateau or see a reduction in quality of life (5, 6).The aims of this study are to describe the long-term outcomes of cardiac intensive care unit (CICU) patients and their primary caregivers; and to explore the feasibility of implementing a complex intervention, designed to support problems associated with PICS and PICS-F, in the year following discharge from the CICU.     

The treatment of resistant warts with intralesional bleomycin: a controlled clinical trial

A controlled double-blind trial was carried out on fifty-nine matched pairs of hand warts in a group of twenty-four patients, with proven resistance to treatment, to study the effectiveness of the intralesional injection of 0.1% solution of bleomycin sulphate in normal saline, compared with a normal saline placebo injected into the paired warts in the same patient. We found that 87.5% of patients showed a more favourable response to bleomycin (P less than 0.001); 76% of the fifty-nine warts treated with bleomycin were cured by one to three injections of up to 0.2 ml of solution. Subsequently 75% of thirty-two patients with resistant hand warts and 66% of fifteen patients with mosaic plantar warts were cured of all their warts. No patient received more than 4 mg of bleomycin. No toxicity was experienced. Local pain was on the whole well tolerated. This form of treatment for resistant warts is reliable, safe and acceptable to patients.     

On the importance of agonist concentration-gradients within isolated tissues. Increased maximal responses of rat vasa deferentia to (–)-noradrenaline after blockade of neuronal uptake

It is assumed often that blockade of agonist uptake processes in isolated tissues results only in shifts to the left of the concentration-response curves to the agonist with no concomitant increase in the maximal response. This may not be true in tissues where diffusion is not fast enough to permit penetration of the agonist to a sufficient number of muscle cells for production of tissue maximal response. Under these circumstances an agonist-concentration gradient is created within the tissue which, when altered, could lead to an increase in the maximal response to the agonist. The increased maximal responses of rat vasa deferentia to (–)-noradrenaline after blockade of neuronal uptake by either cocaine or desmethylimi-pramine have been analysed in terms of a concentration-gradient hypothesis. The data are compared with a theoretical calculation based on a model of restricted diffusion of enzymesubstrates into structured tissues. Both the experimental data and theoretical calculations suggest that an altered concentration-gradient of (–)-noradrenaline within the muscle layers of rat vasa deferentia is responsible for the increased maximal response. The effects of such gradients are discussed in terms of quantitation of drug-receptor phenomena and as a caveat to ascribing increases in maximal responses to post-synaptic effects of uptake inhibitors.