Not just right experience: is it influenced by feelings of guilt?

Individuals with obsessive–compulsive disorder (OCD) experience increased guilt. Further, these individuals often report uncomfortable sensations of things being not quite right (“not just right experiences”—NJREs). As to the relation between these psychological phenomena, it was hypothesized that feelings of guilt may enhance NJRE. In two experiments, we demonstrated that the induction of a guilty emotion resulted in increased NJRE, and this finding was qualified by an interaction with trait guilt. Induced guilt was followed by stronger feelings of things being not just right only in high-trait-guilt participants. In the low-trait-guilt participants NJRE was weaker. Moreover, we found a meaningful relationship between both NJRE and trait guilt and OCD features.     

Autologous in vivo adipose tissue engineering in hyaluronan-based gels--a pilot study

BACKGROUND: There is a major clinical need for strategies for adequately reconstructing the soft tissue defects found after deep burns, tumor resection, or trauma. A promising solution is adipose tissue engineering with preadipocytes, stem-cell derived precursors of the adipose tissue, implanted within biomaterials. This pilot study evaluated hyaluronan gels mixed with autologous undifferentiated preadipocytes in a pig model for their potency to generate new fat. MATERIALS AND METHODS: Preadipocytes were isolated from intra-abdominal pig fat by collagenase digestion, plated on fibronectin-coated culture dishes in Dulbecco's modified Eagle medium/Ham's F12 (Biochrom, Berlin, Germany) combined with 10% pig serum, expanded, and mixed with hyaluronan gel. Two types of gels with varying degrees of amidation of the carboxyl groups were tested (HYADD3, HYADD4). Cell-loaded gels and unseeded controls were injected subcutaneously into the ears of three pigs, explanted at 6 wk, and analyzed histologically. RESULTS: Both cell-loaded specimens were detected macroscopically. They demonstrated a slight volume effect with limited stability after 6 wk. Unloaded HYADD3 and HYADD4 controls could not be identified at the time of explantation. Histology of HYADD3 revealed islets of mature adipocytes and vessels embedded in fat tissue surrounded by gel. In contrast, no fat formation was found in HYADD4 gels when implanted in the ear. CONCLUSIONS: Histological findings demonstrate that HYADD3 is a promising gel for generating adipose tissue. Even though HYADD3 might be a potential material for the reconstruction of small tissue defects, the question remains as to whether the adipose tissue within the gel is attributable to preadipocyte maturation or ingrowth from neighboring tissue.     

Patient mortality after graft failure reduces kidney transplant patient survival only in the long term: an "intention to treat" analysis

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.     

Shockwave lithotripsy and protective role of inosine: early and late evaluation in an experimental model

PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is one of the most common treatments for urinary stones. Despite technological improvements, it may cause side effects varying from minor reversible microscopic damage to severe large renal hematomas. The aim of our experimental study is to assess the efficacy of inosine in avoidance of acute renal damage after SWL. MATERIALS AND METHODS: We used 25 Wistar rats that had previously had left nephrectomy. The rats were divided into three groups: group A consisted of 10 rats undergoing renal SWL; group B consisted of 10 rats that received adjunctive treatment with IP injection of inosine 40 minutes before SWL; and group C consisted of 5 rats that served as controls. N-acetylglucosaminidase (NAG) and lactate dehydrogenase (LDH) concentrations were evaluated 24 hours before and 24 hours after SWL. All the rats were subsequently sacrificed (4 rats in group A and 4 in group B at 48 hours post-SWL, and the remaining rats were sacrificed 30 days post-SWL). Renal tissue was submitted to histologic and electron microscopic examination to assess early and late alterations. RESULTS: NAG and LDH values were significantly increased after SWL in group A (P<0.001), while no significant NAG and LDH differences were detected in group B (P<0.16). Early histologic examination revealed a considerable amount of cellular degeneration in group A with ultrastructural vacuolization and disruption of lysosomal membranes; the tubular features and cellular structures appeared to be well preserved in group B. No late histologic alterations were evident in any of the specimens. CONCLUSIONS: Inosine is helpful and protective in the prevention of early microscopic damage to renal parenchyma due to SWL.     

Discovery of diaryl imidazolidin-2-one derivatives, a novel class of muscarinic M3 selective antagonists (Part 1)

Pharmacophore-based structural identification, synthesis, and structure-activity relationships of a new class of muscarinic M3 receptor antagonists, the diaryl imidazolidin-2-one derivatives, are described. The versatility of the discovered scaffold allowed for several structural modifications that resulted in the discovery of two distinct classes of compounds, specifically a class of tertiary amine derivatives (potentially useful for the treatment of overactive bladder by oral administration) and a class of quaternary ammonium salt derivatives (potentially useful for the treatment of respiratory diseases by the inhalation route of administration). In this paper, we describe the synthesis and biological activity of tertiary amine derivatives. For these compounds, selectivity for the M3 receptor toward the M2 receptor was crucial, because the M2 receptor subtype is mainly responsible for adverse systemic side effects of currently marketed muscarinic antagonists. Compound 50 showed the highest selectivity versus M2 receptor, with binding affinity for M3 receptor Ki = 4.8 nM and for M2 receptor Ki = 1141 nM. Functional in vitro studies on selected compounds confirmed the antagonist activity toward the M3 receptor and functional selectivity toward the M2 receptor.     

Sedation of neurologically impaired children undergoing MRI: a sequential approach

BACKGROUND: The purpose of this retrospective study was to determine the efficacy of a sequential approach meant to rescue failed chloral hydrate sedation and to obtain a low rate of adverse events along with predictable timings in neurologically impaired children undergoing magnetic resonance imaging. METHODS: We retrospectively evaluated 1104 chloral hydrate sedations performed between 2002 and 2004 on 862 children weighing <26 kg. If the desired sedation score (3 on the Skeie Scale) was not reached within 30 min after oral administration of chloral hydrate, sedation was considered as potentially failed, and supplementation with sevoflurane, i.m. or i.v. ketamine, and i.v. pentobarbital and midazolam was started. RESULTS: Twenty-seven sessions failed because of excessive movement. Mean induction time was significantly higher for patients who received supplementation (52.2 min vs 39.1 min), while no differences in recovery and total sedation times were found. Supplementation significantly increased the incidence of respiratory obstruction (4.6% vs 2.4%), although the incidence of other adverse events was unaffected. CONCLUSIONS: Administering up to 1.5 g of chloral hydrate without supplementation was associated with a failure rate of approximately 20%, but the proposed sequential approach enabled us to rescue the majority of failed sedations while maintaining an acceptably low incidence of adverse events.     

Aortic valve surgery in the elderly patient: a retrospective review

Elderly patients are referred with increasing frequency for aortic valve replacement (AVR), due to the ageing of the population and to improved results of surgery. We retrospectively analysed the in-hospital and short-term (up to three years) results of AVR in 185 patients aged >or=75 years, operated on at our institution from January 2000 to December 2003. Follow-up was completed by a telephone interview during January 2005. Hospital mortality was 6.5% (12 patients). A non-elective operation (P=0.001), preoperative NYHA functional class >or=III (P=0.06), and chronic renal failure (P=0.02) were associated with increased operative mortality. Of note, age >or=80 years did not increase the surgical risk. The 4-year actuarial survival was 70.5%, the event-free survival was 60.6%, and almost all of the interviewed patients thought that they had benefited from the operation. Preoperative intubation, a NYHA class >or=III, and a non-elective operation were univariate predictors of a poorer outcome. Our data show that aortic valve replacement may be performed with low morbidity and mortality in the elderly patient (age >or=75 years), and that an age >or=80 years neither increases the surgical risk, nor significantly worsens the short-term outcome.     

Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models

Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-beta1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation.