Transplant data: sources, collection and research considerations, 2004

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.     

Mental object rotation in Parkinson's disease.

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.     

Opposite rank order of potency for alpha-2 adrenoceptor agonists on water and solute excretion in the rat: two sites and/or receptors?

Preliminary studies determined that, unlike other purported alpha-2 adrenoceptor agonists, 2,6-dimethyl clonidine (2,6-DMC) increased urine flow rate independent of vasopressin. We therefore compared the dose-response curves of three alpha-2 adrenoceptor agonists, clonidine, UK 14,304 and 2,6-DMC. Unilaterally nephrectomized Sprague-Dawley rats were anesthetized and the left kidney was exposed and the ureter cannulated. A 31-gauge needle was advanced into the renal artery to permit direct intrarenal infusion of the study drugs. All three agonists produced a dose-related increase in urine flow rate and sodium excretion. A clear opposite rank order of potency was observed when the urine flow rate was analyzed as free water and osmolar clearance. For free water clearance, clonidine much greater than UK 14,304 much greater than 2,6-DMC, with 2,6-DMC producing little change. The effect on osmolar clearance was opposite with 2,6-DMC much greater than clonidine = UK 14,304. The V2 antagonist [1-(beta-mercapto-beta,beta-pentamethylene-proprionic acid), 2-d-isoleucine,4-isoleucine]arginine-vasopressin blocked the effects of clonidine but not 2,6-DMC. In a water-loaded rat model, 2,6-DMC but not clonidine increased the delivery of filtrate out of the proximal segments of the nephron. These results are consistent with the postulate that lower doses of 2,6-DMC increase solute excretion independent of vasopressin, possibly in proximal segments of the nephron. Clonidine on the other hand increases free water clearance and this effect is mediated through an interaction with the renal actions of vasopressin. Whether these disparate effects represent two distinct receptors or two sites of alpha-2 adrenoceptors in the kidney is not known.     

Allodynia in rats infected with varicella zoster virus—a small animal model for post-herpetic neuralgia

The most common complication of herpes zoster is post-herpetic neuralgia (PHN), which has been defined as severe pain occurring 1 month after rash onset or persisting for greater than 3 months. PHN is classed as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful. The development of therapies to treat PHN has been hampered by the lack of animal models, which mimic the clinical situation. We have previously reported that varicella zoster virus (VZV) infection in the rat results in mechanical allodynia and thermal hyperalgesia. Here, we report that following VZV infection of the left footpad rats develop a chronic mechanical allodynia, which is present for longer than 60 days post-infection and which resolves by 100 days PI. The model is robust and reproducible with animals consistently developing allodynia by 3 days PI and continuing to present with symptoms for at least 30 days. The reproducible nature of the induction and course of the allodynia allows the use of this model to determine the effect of various compounds on, and to investigate the pathogenic mechanisms underlying the development of VZV-induced allodynia. Comparative studies using HSV-1 show that the induction of the chronic allodynia is VZV-specific and is not a result is of virus replication-induced tissue damage or accompanying inflammation.Therefore, we propose that the rat VZV infection model could prove useful in studying the mechanisms underlying post-herpetic neuralgia.     

The meaning of spirituality: a literature review

This paper presents a literature review in relation to the meaning of spirituality. It is proposed that meeting the spiritual needs of patients is a fundamental part of providing holistic nursing care, but that the assessment and meeting of those needs is impeded by inadequate definitions and conceptual frameworks. It should not be assumed that spirituality is either synonymous, or coterminous, with religion, and it is suggested that to adopt this restrictive view is unhelpful in the provision of individualized care. Reflection on the literature reveals that the self, others and 'God' provide the key elements within a definition of spirituality, and that other emerging themes namely meaning, hope, relatedness/connectedness, beliefs/belief systems and expressions of spirituality, can be articulated in the context of those three key elements. In particular, it is proposed that the nature of 'God' may take many forms and, essentially, is whatever an individual takes to be of highest value in his/her life. It is suggested that the themes emerging from the literature can be utilized as a framework to give practitioners and researchers a direction for future exploration of the concept of spirituality.     

Treating the cognitive deficits of schizophrenia

Schizophrenia is characterized by significant cognitive impairments that predict impairment in multiple domains of community outcome. Pharmacologic and psychosocial treatments are available that address these cognitive deficits. There is growing evidence that patients taking second-generation antipsychotic medications perform better on tests of cognitive function than those taking conventional neuroleptics. In addition, there have been a number of medications from other classes being investigated as cognitive enhancers for schizophrenia. Cognitive rehabilitation approaches focus on bypassing, compensating for, or remediating observed impairments in cognitive function. Outcomes for patients have been improved by cognitive remediation, errorless learning, and the use of supportive environments. Combining the newest pharmacologic interventions for cognitive dysfunction with state of the art psychosocial treatments aimed at ameliorating or bypassing deficits is likely to produce the most favorable outcomes for individuals with schizophrenia.     

Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.