Acute renal cortical necrosis due to acquired antiprotein S antibodies

Although varicella is a common disease of childhood, renal complications are quite rare. We report here the interesting case of a-22 month-old boy exhibiting renal cortical necrosis related to an acquired protein S deficiency following varicella. Ten days after the vesicle eruption appearance, he presented with ecchymosed heels, oligoanuric kidney failure, anemia [hemoglobin (Hb) 78 g/L], schizocytosis (2.5%), but normal platelet count. Kidney sonography and magnetic resonance imaging evoked renal cortical necrosis. All together, these features suggested acquired protein S deficiency secondary to varicella. Strikingly, it was confirmed by a dramatic decrease in protein S plasma activity and a huge increase in immunoglobulin (Ig)G antibodies against protein S in the plasma. Anticoagulation therapy in addition with plasmapheresis and steroid pulses allowed a dramatic decrease in the antibodies against protein S and recovery of normal protein S activity. Undelayed diagnosis and treatment did not avoid kidney insufficiency but prevented life-threatening complications. In the light of this case report, protein S deficiency due to antibody inhibition should be carefully monitored anytime in the context of varicella when kidney insufficiency or necrosis occurs.     

Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey

After injury, regrowth of axons in mammalian adult central nervous system is highly limited. However, in monkeys subjected to unilateral cervical lesion (C7-C8 level), neutralization of an important neurite outgrowth inhibitor, Nogo-A, stimulated axonal sprouting caudal to the lesion, accompanied by enhanced functional recovery of manual dexterity, compared with lesioned monkeys treated with a control antibody (Freund et al. [2006] Nat. Med. 12:790-792). The present study aimed at comparing the same two groups of monkeys for axonal sprouting rostral to the cervical lesion. The corticospinal tract was labeled by injecting the anterograde tracer biotinylated dextran amine into the contralesional motor cortex. The corticospinal axons were interrupted at the level of the lesion, accompanied by retrograde axonal degeneration (axon dieback), reflected by the presence of terminal retraction bulbs. The number of terminal retraction bulbs was lower in anti-Nogo-A antibody treated monkeys, and, when present, they were found closer to the lesion than in control-antibody treated monkeys. Compared with control antibody treated monkeys, the anti-Nogo-A antibody treated monkeys exhibited an increased cumulated axon arbor length and a higher number of axon arbors going in the medial direction from the white to the gray matter. Higher in the cervical cord (at C5 level), the anti-Nogo-A treatment enhanced the number of corticospinal fibers crossing the midline, suggesting axonal sprouting. Thus, the anti-Nogo-A antibody treatment enhanced axonal sprouting rostral to the cervical lesion; some of these fibers grew around the lesion and into the caudal spinal segments. These processes paralleled the observed improved functional recovery.     

Safety of endovascular treatment of intracranial aneurysms with a new,complex shaped Guglielmi detachable coil

Introduction The Guglielmi detachable coil (GDC) 360°, a new complex shaped bare platinum coil, became available in Europe for aneurysm treatment in September 2005. The purpose of this study was to assess the feasibility and safety of selective embolization of intracranial aneurysms with the GDC 360° in 52 consecutive patients. Methods All patients included in this study were registered in a prospectively maintained database. We assessed the patient clinical history, aneurysm shape and dimensions, technical details and complications of the procedures, degree of aneurysm occlusion, and clinical findings upon discharge. In all patients, the first coil deployed was a GDC 360°. Results Over a 6-month period, we intended to treat 52 aneurysms with the GDC 360° in 52 patients. Of these 52 patients, 42 (81%) were treated in the context of subarachnoid haemorrhage. In 51 of 52 patients, the underlying aneurysm was successfully treated by coil embolization. Six procedures (11.5%) were complicated by the formation of thrombus in the parent artery during the intervention. One patient suffered a stroke related to the procedure. Angiograms obtained immediately after the procedure showed complete occlusion of the aneurysmal sac in 38 of 51 procedures (74.5%), a neck remnant in 11 (21.6%), and a residual aneurysm in 2 (3.9%). In 43 of 51 patients (84.3%), clinical assessment demonstrated independent clinical status, whereas 7 patients (13.7%) required assistance in the activities of daily living upon hospital discharge. One patient (2.0%) died after development of a severe vasospasm 10 days after the endovascular procedure. Conclusion The GDC 360° can be safely used for the endovascular occlusion of intracranial aneurysms.     

Neutralization of interleukin-1β modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice

Interleukin-1β (IL-1β) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1β neutralizing antibody IgG2a/k (1.5 μg/mL) or control antibody was infused at a rate of 0.25 μL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1–7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1β in vitro . IL-1β neutralization attenuated the CCI-induced cortical and hippocampal microglial activation ( P  <   0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils ( P  <   0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1β neutralization ( P  <   0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue ( P  <   0.05). In brain-injured animals, IL-1β neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits ( P  <   0.05) without influencing neurological motor function. Our results indicate that IL-1β is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.     

Using the health assessment questionnaire to estimate preference-based single indices in patients with rheumatoid arthritis

OBJECTIVE: To estimate the relationship between preference-based measures, EuroQol (EQ-5D) and SF-6D, and the Health Assessment Questionnaire (HAQ) disability index (DI) in patients with rheumatoid arthritis (RA), and to characterize components that are predictors of health utility. METHODS: Patients with RA participating in 2 studies in the UK (n = 151) and Canada (n = 319) completed the HAQ, EQ-5D, and Short Form 36 (SF-36). The SF-36, a generic measure of quality of life, was converted into the preference-based SF-6D. From these results we developed models of the relationship between the HAQ and SF-6D and EQ-5D using various regression analyses. RESULTS: The optimal model developed for the EQ-5D entered levels for each item as independent variables (model 5). A root mean square error (RMSE) of 0.18 suggested relatively good predictive ability. For the SF-6D, RMSEs were lower (0.09), suggesting better predictions than for the EQ-5D, but models with more explanatory variables did not improve results (model 2 or 4 optimal). The models were able to predict actual SF-6D and EQ-5D across the range of the HAQ DI. CONCLUSION: Our approach enabled calculations of quality-adjusted life years from existing trials where only the HAQ was measured. All aspects of the HAQ may not be reflected in the preference-based measures, and this method is suboptimal to direct measurement of health state utility in clinical trials. Given this limitation, our approach provides an alternative for researchers who need health-state utility values, but had not included a preference-based measure in their clinical study because of resource constraints or a desire to limit patient burden.     

Endoscopy/surveillance in inflammatory bowel disease

Patients with chronic colitis from inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). Previously, to ameliorate this, prophylactic total colectomy was offered to patients who had chronic ulcerative colitis (UC); however, research has identified less invasive management options through better understanding of the pathogenesis of cancer in chronic inflammation, a more uniform histologic diagnosis by pathologists, and proper surveillance colonoscopy techniques. This article reviews the pathogenesis of neoplasia in IBD, and then reviews the risk factors for CRC in IBD, surveillance guidelines and their limitations, surveillance techniques, ileal pouch dysplasia, and chemoprevention. Although data for CRC risk in Crohn's disease (CD) are not as extensive, it has been suggested that the risks are comparable to UC.     

Eosinophilic cystitis induced by bacillus Calmette-Guerin (BCG) intravesical instillation

Eosinophilic cystitis is a rare and uncommon inflammatory bladder disease, in which the pathophysiology is unclear; only a few cases of such disease induced by intravesical instillations have been described. We report a case of eosinophilic cystitis after intravesical bacillus Calmette-Guerin (BCG) instillation for nonmuscle-invasive transitional cell carcinoma of the bladder. To our knowledge, this report is the first case of eosinophilic cystitis induced by intravesical BCG therapy.