The value of incomplete mouse models of Alzheimer's disease

To study Alzheimer's disease (AD), a variety of mouse models has been generated through the overexpression of the amyloid precursor protein and/or the presenilins harboring one or several mutations found in familial AD. With aging, these mice develop several lesions similar to those of AD, including diffuse and neuritic amyloid deposits, cerebral amyloid angiopathy, dystrophic neurites and synapses, and amyloid-associated neuroinflammation. Other characteristics of AD, such as neurofibrillary tangles and nerve cell loss, are not satisfactorily reproduced in these models. Mouse models that recapitulate only specific aspects of AD pathogenesis are of great advantage when deciphering the complexity of the disease and can contribute substantially to diagnostic and therapeutic innovations. Incomplete mouse models have been key to the development of Abeta42-targeted therapies, as well as to the current understanding of the interrelationship between cerebral beta-amyloidosis and tau neurofibrillary lesions, and are currently being used to develop novel diagnostic agents for in vivo imaging.     

Characteristics of incidental prostatic adenocarcinoma in contemporary radical cystoprostatectomy specimens

OBJECTIVES: To investigate the relationship between prostate-specific antigen (PSA) level and tumour volume for incidental adenocarcinoma of the prostate found in cystoprostatectomy (CP) specimens, and to analyse the incidence of clinically significant prostate cancers in CP specimens and the biochemical recurrence of incidental prostate cancers on short-term follow up. PATIENTS AND METHODS: Complete data from 97 of 105 prostates from CP specimens were available. Prostates were thoroughly analysed and sectioned at 2 mm intervals. PSA levels and the findings at digital rectal examination before surgery were obtained prospectively. None of the patients had any evidence of prostate cancer before CP. RESULTS: Incidental prostate cancer was detected in 58 of 97 (60%) of the CP specimens; of these, 31 (53%) were significant according to the definition of Stamey et al. There was a weak correlation between tumour volume and PSA level, weighted solely by the four larger-volume cancers. The median PSA level for patients with and without prostate cancer was not significantly different (3.1 vs 1.1 ng/mL, P = 0.06). The follow-up of the 35 patients alive with prostate cancer showed four PSA recurrences (PSA >0.02 ng/mL) with one distant metastasis after a median follow-up of 3 years. None of the patients with insignificant tumours developed biochemical recurrence. CONCLUSIONS: The weak correlation between PSA level and tumour volume in these patients supports the argument that PSA is largely produced by benign prostatic hyperplasia and is therefore a poor screening tool for asymptomatic healthy men. Most incidental prostate cancers in CP specimens are significant, contrary to previous analyses, but have little practical importance in terms of oncological outcome.     

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury. Received: 23 March 2001 / Revised: 23 August 2001 / Accepted: 24 August 2001     

Mass casualty incidents with multiple burn victims: Rationale for a Swiss burn plan

Introduction

Mass casualty incidents involving victims with severe burns pose difficult and unique problems for both rescue teams and hospitals. This paper presents an analysis of the published reports with the aim of proposing a rational model for burn rescue and hospital referral for Switzerland.

Methods

Literature review including systematic searches of PubMed/Medline, reference textbooks and journals as well as landmark articles.

Results

Since hospitals have limited surge capacities in the event of burn disasters, a special approach to both prehospital and hospital management of these victims is required. Specialized rescue and care can be adequately met and at all levels of needs by deploying mobile burn teams to the scene. These burn teams can bring needed skills and enhance the efficiency of the classical disaster response teams. Burn teams assist with both primary and secondary triage, contribute to initial patient management and offer advice to non-specialized designated hospitals that provide acute care for burn patients with Total Burn Surface Area (TBSA) <20–30%. The main components required for successful deployments of mobile burn teams include socio-economic feasibility, streamlined logistical implementation as well as partnership coordination with other agencies including subsidiary military resources.

Conclusions

Disaster preparedness plans involving burn specialists dispatched from a referral burn center can upgrade and significantly improve prehospital rescue outcome, initial resuscitation care and help prevent an overload to hospital surge capacities in case of multiple burn victims. This is the rationale behind the ongoing development and implementation of the Swiss burn plan.     

Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy

OBJECTIVES: Based on our recently published anatomic studies, we present the most recent refinement of the endoscopic extraperitoneal radical prostatectomy (EERPE), the intrafascial nerve-sparing EERPE (nsEERPE). METHODS: As part of the intrafascial technique, the dissection plane is directly on the prostatic capsule, freeing the prostate laterally from its thin surrounding fascia that contains small vessels and nerves. The technique enables puboprostatic ligament preservation, leaving intact endopelvic fascia, periprostatic fascia, and neurovascular bundles. The operation was performed in 150 patients with indications for nerve-sparing procedure. RESULTS: The mean operative time was 131 min (range: 50-210 min) and the mean catheterization time was 5.9 d (range: 4-20 d). Twelve months postoperatively, 94.3% of the patients were continent (no need for pads), 4.6% had minimal stress incontinence, and one patient required >2 pads/d. At the 12-mo follow-up, the potency rates (erections sufficient for intercourse with or without the use of phosphodiesterase 5 [PDE5] inhibitors) of the patients who underwent bilateral intrafascial nsEERPE were 89.7% (age: 44-55 yr), 81.1% (age: 56-65 yr), and 61.9% (age: >65 yr). Positive surgical margins in pT2 and pT3 tumors were 4.5% and 29.4%, respectively. CONCLUSIONS: The intrafascial nsEERPE enables the dissection of the prostate with limited trauma to the surrounding fascias and the enclosed neurovascular bundles. We propose that the preserved neurovascular bundles with intrafascial nsEERPE are more viable. The results advocate this proposition.     

Role of stone analysis in metabolic evaluation and medical treatment of nephrolithiasis

BACKGROUND AND PURPOSE: Comprehensive metabolic evaluation has become an important aspect of the management of recurrent nephrolithiasis, yet the role of stone analysis is often neglected or perhaps underestimated. The purpose of this study was to determine the role of stone analysis in medical decision making in patients with recurrent nephrolithiasis. MATERIALS AND METHODS: We evaluated 100 consecutive stone-forming patients who had undergone compositional stone analysis as well as comprehensive metabolic evaluation at our institution. An analysis of stone composition in relation to metabolic disturbances was performed. Patients were stratified into two groups: calcium and non-calcium stone formers. RESULTS: Patients having non-calcium stones were found to have a metabolic analysis reflecting specific metabolic disorders. Alternatively, patients with calcium stones were heterogeneous with regard to metabolic disorders, but there was a significant likelihood of renal tubular acidosis in those patients with calcium phosphate calculi. On the basis of these results, a simplified metabolic evaluation and nonselective medical therapy based on stone composition was formulated to facilitate assessment, management, and monitoring of stone disease. CONCLUSIONS: Compositional stone analysis should be an integral part of the metabolic evaluation of patients with nephrolithiasis. Moreover, stone analysis alone may provide guidance for therapeutic treatment and obviate a formal metabolic evaluation.     

光学相干断层成像技术诊断深Ⅱ度烧伤创面实验研究

目的 评估光学相干断层成像技术(OCT)在诊断烧伤创面深度方面的应用价值.方法 应用自制的小鼠蒸气烫伤装置,制作Skh-1小鼠深Ⅱ度烫伤模型,分别于伤后3 h、3 d和8 d以OCT扫描创面行动态检测,同步采集创面组织行组织病理学检查;同时扫描小鼠正常部位皮肤并行组织病理学检查. 结果蒸气烫伤小鼠皮肤真皮胶原降解,与其正常部位皮肤相比,在OCT扫描检测中表现为双折射光信号的丢失或减弱,其变化强度与创面病变过程相关,且与组织病理学切片结果一致. 结论 OCT作为无创的创面检测技术,可用于烧伤创面动态检测.     

Role of prefrontal and anterior cingulate regions in decision-making processes shared by memory and nonmemory tasks

In the episodic retrieval (ER) domain, activations in right dorsolateral prefrontal cortex (DLPFC) are often attributed to postretrieval monitoring. Yet, right DLPFC activations are also frequently found during nonmemory tasks. To investigate the role of this region across different cognitive functions, we directly compared brain activity during ER and visual perception (VP) using event-related functional magnetic resonance imaging. In the ER task, participants decided whether words were old or new, whereas in the VP task, they decided which of the two colored screen areas was larger. In both tasks, each decision was followed by a confidence rating. The main finding was that right DLPFC (Brodmann area 46/10) activity was greater for low- than for high-confidence decisions in both tasks, demonstrating a general role in decision making. Even when reaction times (RTs) were included in the model, confidence remained the significant predictor of activity, suggesting that right DLPFC is involved in discontinuous evaluation rather than in continuous monitoring. In contrast, activity in anterior cingulate cortex was not only greater for low-confidence decisions but also increased with RT, reflecting a role in continuous conflict monitoring. Overall, the results demonstrate how direct cross-function comparisons clarify the generality and specificity of the functions of various brain regions.