Chloride: The queen of electrolytes?

BackgroundChannelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general do not allocate chapters exclusively on hypochloremia or hyperchloremia and information on chloride other than channelopathies is scattered in the literature.Study designTo systematically review the function of chloride in man, data for this review include searches of MEDLINE, PubMed, and references from relevant articles including the search terms “chloride,” “HCl,” “chloride channel” “acid-base,” “acidosis,” “alkalosis,” “anion gap” “strong anion gap” “Stewart,” “base excess” and “lactate.” In addition, internal medicine, critical care, nephrology and gastroenterology textbooks were evaluated on topics pertaining the assessment and management of acid-base disorders, including reference lists from journals or textbooks.ConclusionChloride is, after sodium, the most abundant electrolyte in serum, with a key role in the regulation of body fluids, electrolyte balance, the preservation of electrical neutrality, acid-base status and it is an essential component for the assessment of many pathological conditions. When assessing serum electrolytes, abnormal chloride levels alone usually signify a more serious underlying metabolic disorder, such as metabolic acidosis or alkalosis. Chloride is an important component of diagnostic tests in a wide array of clinical situations. In these cases, chloride can be tested in sweat, serum, urine and feces. Abnormalities in chloride channel expression and function in many organs can cause a range of disorders.     

Tissue thiamine deficiency as potential cause of delayed graft function after kidney transplantation: thiamine supplementation of kidney donors may improve transplantation outcome

Delayed graft function is an important medical problem after renal transplantation. It occurs in approximately 30% of cases, and is not only associated with more prolonged and complicated hospitalisation, but also with earlier graft loss on the long-term. Delayed graft function is the consequence of acute tubular necrosis caused by ischaemia-reperfusion injury, with insufficiently opposed toxic effects of reactive oxygen species and insufficient ATP regeneration. An optimal tissue thiamine status is pivotal for scavenging of reactive oxygen species and regeneration of ATP. There are several reasons to suppose that tissue thiamine availability is suboptimal in donor kidneys prior to reperfusion in transplantation. These reasons include a high prevalence of untreated thiamine deficiency at admission of donors to intensive care units, quick exhaustion of body thiamine stores during periods of non-feeding or inappropriate feeding during hospital stays of donors, and loss of the water-soluble vitamin into water-based organ preservation solutions. We therefore hypothesize that a suboptimal tissue thiamine status is a cause of delayed graft function after renal transplantation, and that it can be prevented with thiamine supplementation.     

Skin autofluorescence is a strong predictor of cardiac mortality in diabetes

OBJECTIVE: Advanced glycation end products (AGEs) are biomarkers of metabolic stress and are thought to contribute to the increase of coronary heart disease (CHD) in diabetes. Tissue autofluorescence is related to the accumulation of AGEs. The aim of the present study was to evaluate the relationship between skin autofluorescence and metabolic burden (hyperglycemia and hyperlipidemia) and its relationship with CHD and mortality. RESEARCH DESIGN AND METHODS: Skin autofluorescence was measured noninvasively with an autofluorescence reader in 48 type 1 and 69 type 2 diabetic patients and 43 control subjects. The presence of CHD was observed at baseline and mortality during a follow-up period of 5 years. RESULTS: Autofluorescence correlated with mean A1C, triglycerides, and LDL. Autofluorescence values further increased with age, microalbuminuria, dialysis treatment, and diabetes duration. Autofluorescence was strongly related to the presence of CHD (odds ratio 7.9) and predicted mortality (3.0). Multivariate analysis showed that autofluorescence was more strongly associated with CHD and mortality compared with A1C, triglycerides, and LDL. CONCLUSIONS: Skin autofluorescence is strongly related to cumulative metabolic burden. Skin autofluorescence seems strongly associated with cardiac mortality and may provide important clinical information for risk assessment.     

The 34th Walter J. Zeiter lecture: creating the future of PM&R: building on our past

The founders of the field of physical medicine and rehabilitation (PM&R) took advantage of a confluence of political, technical, and economic opportunities to launch our specialty. In the process, they expressed their values of belief in the importance of function, the team approach to health care, the utility of physical agents and modalities in the management of neuromuscular conditions, the impact of education for our patients and their families, the rights of persons with a disability (PWD), and the responsibility of our field to advocate for public policy issues concerned with the needs of PWD. Advances in the technology of health care delivery and biomedicine will shape our future. Specific trends and factors are addressed. Equally important will be the political dimension, including the aging of our global population, and the economic consequences of health insurance pressures. The field of PM&R should focus on activities that take advantage of emerging trends but are rooted in our traditional values. In particular, the field should look forward to the massive growth of populations in need of our services because of aging and longevity, the emerging global health community, and our increasing technical capacity to impact improvements in health and function. The field is charged to preserve awareness of our core values, to support the common good of research, to keep the use of new and emerging technology in check to serve the needs of our patients, to continue our advocacy for social justice for PWD, and to embrace the emerging global community.     

Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia

Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.     

Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy

Aims/hypothesis The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence Reader (AFR), could be used to assess skin AGE accumulation. We evaluated the relationship between skin autofluorescence and the severity of diabetic neuropathy.Materials and methods Skin autofluorescence in arbitrary units (AU) was assessed in 24 diabetic patients with a history of neuropathic foot ulceration (NP⁺), 23 diabetic patients without clinical neuropathy (NP^–) and 21 control subjects, using the AFR. Arterial occlusive disease was excluded in all. The severity of foot ulceration was assessed by the Wagner score. Peripheral nerve function was assessed by neurography, measuring motor and sensory nerve conduction velocity and amplitude of the median, peroneal and sural nerves. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were measured by Finapres to assess autonomic nervous function.Results Autofluorescence was increased in NP^– compared with control subjects. In NP⁺ patients, autofluorescence was further increased and correlated with the Wagner score. Autofluorescence correlated negatively with nerve conduction velocity and amplitude, HRV and BRS in both NP⁺ and NP^– groups. Autofluorescence correlated with age, diabetes duration, mean HbA₁c of the previous year, serum creatinine level, presence of microalbuminuria and severity of diabetic retinopathy.Conclusions/interpretation Skin autofluorescence correlates with the severity of peripheral and autonomic nerve abnormalities in diabetes, even before being clinically manifest. The AFR may be a convenient and rapid clinical tool for assessing risk of progression of long-term diabetic complications.     

对发展中国家改善用药的10点建议

WHO建议改善药品管理的工作要在国家药物政策保障之下.在许多国家,执行国家药物政策的机制是实施国家基本药物计划,其要点是强调公共领域的药品选择、采购、流通与使用的合理性.不适当的处方使医疗质量降低并导致资源浪费.本文以探讨在国家药物政策范畴内鼓励更合理地使用药品的问题为重点,在已有证据的基础上,详细阐明基本药物计划内容中的合理用药问题.本文评述了在发展中国家改善用药状况的有效策略及最新知识,并为决策者与管理者提出达到改善用药目标的建议.     

A polymorphism in the gene encoding carnosinase (CNDP1) as a predictor of mortality and progression from nephropathy to end-stage renal disease in type 1 diabetes mellitus

Aims/hypothesis

Homozygosity for a five leucine repeat (5L–5L) in the carnosinase gene (CNDP1) has been found to be cross-sectionally associated with a low frequency of diabetic nephropathy (DN), mainly in type 2 diabetes. We prospectively investigated in patients with type 1 diabetes whether: (1) 5L–5L is associated with mortality; (2) there is an interaction of 5L–5L with DN or sex for prediction of mortality; and (3) 5L–5L is associated with progression to end-stage renal disease (ESRD).

Methods

In this prospective study in white European patients with type 1 diabetes, individuals with DN were defined by persistent albuminuria ≥300 mg/24 h. Controls without nephropathy were defined by persistent (>15 years) normoalbuminuria <30 mg/24 h. Leucine repeats were assessed with a fluorescent DNA analysis system. Onset of ESRD was defined by need to start chronic dialysis or kidney transplantation.

Results

The study involved 916 patients with DN and 1,170 controls. During follow-up for 8.8 years, 107 patients (14%) with 5L–5L died compared with 182 patients (13.8%) with other genotypes (p?=?0.99). There was no significant interaction of 5L–5L with DN for prediction of mortality (p?=?0.57), but a trend towards interaction with sex (p?=?0.08). In patients with DN, HR for ESRD in 5L–5L vs other genotypes was not constant over time, with increased risk for 5L–5L beyond 8 years of follow-up (p?=?0.03).

Conclusions/interpretation

CNDP1 polymorphism was not associated with mortality, and nor was there an interaction of this polymorphism with DN for prediction of mortality in patients with type 1 diabetes. CNDP1 polymorphism predicts progression to ESRD in patients with DN, but only late after baseline measurements.     

Acute acalculous cholecystitis: not only in the intensive care department

In two men aged 65 and 40 years with abdominal pain, the diagnosis 'acute acalculous cholecystitis' (AAC) could be reached only after exploratory laparotomy. The first patient was initially admitted to the coronary-care department because of known atherosclerotic vascular disease; he died a few days after the operation due to sepsis. The second patient recovered satisfactorily after admission to intensive care because of haemodynamic instability. AAC is an illness with a non-specific clinical presentation and incomplete radiologic imaging. AAC is more frequently seen in outpatients than in acutely ill inpatients, especially in older male patients who have atherosclerotic vascular disease. Diagnostic and therapeutic delay leads to gangrene, empyema and perforation, resulting in a high mortality. To improve the outcome, a high and early index of suspicion is needed. Hepatobiliary scintigraphy should be included in the diagnostic pathway.