Acute Renal Failure in Association with Community-Acquired Clostridium difficile Infection and McKittrick-Wheelock Syndrome

We report the case of a 65-year-old Caucasian woman who experienced two separate episodes of acute renal failure within an 18-month period, both requiring emergency admission and complicated treatment. Each episode was precipitated by hypovolaemia from intestinal fluid losses, but from two rare and independent pathologies. Her first admission was attributed to community-acquired Clostridium difficile-associated diarrhoea (CDAD) and was treated in the intensive therapy unit. She returned 18 months later with volume depletion and electrolyte disturbances, but on this occasion a giant hypersecretory villous adenoma of the rectum (McKittrick-Wheelock syndrome) was diagnosed following initial abnormal findings on digital rectal examination by a junior physician. Unlike hospital-acquired C. difficile, community-acquired infection is not common, although increasing numbers are being reported. Whilst community-acquired CDAD can be severe, it rarely causes acute renal failure. This case report highlights the pathological mechanisms whereby C. difficile toxin and hypersecretory villous adenoma of the rectum can predispose to acute renal failure, as well as the values of thorough clinical examination in the emergency room, and early communication with intensivist colleagues in dire situations

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Re-amputation occurrence in the diabetic population in South Wales, UK

The incidence of re-amputation following lower extremity amputations (LEA) among the diabetic patients referred to the Artificial Limb and Appliance Centers (ALAC) in South Wales, UK, was investigated. Manual and electronic data-gathering systems were used to extract the medical records of 473 people with various causes of LEA referred to the ALAC in South Wales during 2001–2003. The data included demographic information, causes of amputation and occurrence of various levels of re-amputation. Two hundred and five subjects with diabetes underwent 316 amputations, 44 were foot amputations and 272 major amputations on the ipsilateral and contra-lateral sides. Of the diabetic patients, 45·9% with single LEA underwent re-amputations with 22% incidence of contra-lateral LEA within 2 years. In comparison, 15% underwent re-amputations in the non diabetic dysvascular patients. Ipsilateral re-amputations occurred much earlier (average 21 weeks) compared with the contra-lateral amputations which took an average of 82 weeks following the first amputation. Nearly half of the diabetic patients with single LEA referred for rehabilitation underwent re-amputations within 2 years; out of which 22% of the patients underwent contra-lateral LEA. Although the progression of level of amputations does not follow a particular pattern, re-amputation on the contra-lateral side occurred almost four times later than that on the ipsilateral side

Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling

Stress affects the hippocampus, a brain region crucial for memory. In rodents, acute stress may reduce density of dendritic spines, the location of postsynaptic elements of excitatory synapses, and impair long-term potentiation and memory. Steroid stress hormones and neurotransmitters have been implicated in the underlying mechanisms, but the role of corticotropin-releasing hormone (CRH), a hypothalamic hormone also released during stress within hippocampus, has not been elucidated. In addition, the causal relationship of spine loss and memory defects after acute stress is unclear. We used transgenic mice that expressed YFP in hippocampal neurons and found that a 5-h stress resulted in profound loss of learning and memory. This deficit was associated with selective disruption of long-term potentiation and of dendritic spine integrity in commissural/associational pathways of hippocampal area CA3. The degree of memory deficit in individual mice correlated significantly with the reduced density of area CA3 apical dendritic spines in the same mice. Moreover, administration of the CRH receptor type 1 (CRFR1) blocker NBI 30775 directly into the brain prevented the stress-induced spine loss and restored the stress-impaired cognitive functions. We conclude that acute, hours-long stress impairs learning and memory via mechanisms that disrupt the integrity of hippocampal dendritic spines. In addition, establishing the contribution of hippocampal CRH–CRFR1 signaling to these processes highlights the complexity of the orchestrated mechanisms by which stress impacts hippocampal structure and function