Further morphological and biochemical observations on early low dose streptozocin diabetes in mice.

Conflicting published data regarding the role of macrophages and other cell types during the early stages of diabetes mellitus led us to further study this problem. To this end we diabetized mice, using low doses of streptozocin (STZ), 40 mg/kg body wt/day/5 days, and processed their pancreatic tissue for immunocytochemistry and ultrastructural observations; immunohistochemistry was performed on days 5 and 18 after the first STZ injection, and islets were observed ultrastructurally on days 5, 9, 10, and 18. Animals were tested for fasting serum glucose, and isolated islets were assayed for insulin secretion capacity. Immunohistology demonstrated that expression of major histocompatability complex class 2 antigens is strongly induced by multiple, low dose STZ treatments prior to impaired insulin release, and that different types of cells within the islet are capable of expressing Ia molecules. Ultrastructurally we found (a) a small number of macrophages (most probably resident monocytes/macrophages) containing B-cell debris, that were located close to either damaged or intact B cells; (b) a large number of recruited macrophages in a vascular or perivascular position; and (c) macrophages recognizable in the exocrine portion, close to the islets, occasionally containing exocrine cell debris. This led us to believe that recruited macrophages play an important role in the early islet-infiltrating stage.     

Clinical impact of CCM mutation detection in familial cavernous angioma

Introduction and background A 3-year-old Bosnian girl with a large symptomatic brainstem and multiple supratentorial cavernous angiomas, who underwent neurosurgical treatment, is presented. As multiple cavernomas are more common in familial cases, genetic analyses and neuroradiological imaging were performed in the patient and her parents to see whether there was any evidence for inheritance. This information is important for genetic counseling and provision of medical care for at-risk relatives. Currently, no recommendation is available on how to manage these cases.Results Genetic analyses demonstrated a novel CCM1 frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance imaging of the mother revealed multiple supratentorial lesions, whereas analogous imaging of the father showed no pathological findings.Conclusion This case exemplifies that seemingly sporadic cases with multiple lesions might well be hereditary and that presymptomatic genetic testing of family members may identify relatives for whom clinical and neuroradiological monitoring is indicated.     

Sirolimus and mycophenolate mofetil as calcineurin inhibitor-free immunosuppression in a cardiac transplant patient with chronic renal failure.

Chronic renal failure triggered by calcineurin inhibitor (CNI)-based immunosuppression is a common complication after cardiac transplantation. Sirolimus and mycophenolate mofetil (MMF) are 2 newer immunosuppressive agents with no documented nephrotoxic side effects. This case report describes a patient with ongoing chronic renal failure 10 months after cardiac transplantation on cyclosporine-based immunosuppressive therapy. Conversion of the immunosuppressive regimen from cyclosporine to sirolimus and MMF resulted in freedom from acute rejection, excellent cardiac graft function and consistently improved renal function. This case illustrates the beneficial potential of sirolimus and MMF as CNI-free and safe long-term immunosuppression in a patient with chronic renal failure after heart transplantation.     

Long-term benefit to pallidal deep brain stimulation in a case of dystonia secondary to pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with onset in childhood and rapid progression. There is no causative and insufficient symptomatic drug therapy. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been reported to improve motor function. Most case reports, however, are limited to short observational periods. The impact of DBS on the progression and life expectancy in PKAN is unknown. We present a 5-year outcome and video documentation of bilateral GPi-DBS of an adolescent patient suffering from genetically defined PKAN.     

How often do asymptomatic healthcare workers cause methicillin-resistant Staphylococcus aureus outbreaks? A systematic evaluation.

A systematic search was performed to identify outbreaks of methicillin-resistant Staphylococcus aureus infection and colonization caused by healthcare workers (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the cause. The frequent practice of screening asymptomatic HCWs should be reconsidered.     

Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

Betahistine: a retrospective synopsis of safety data.

Betahistine is a structural analogue of histamine that is prescribed for the treatment of vestibular disorders such as Ménière's disease and the symptomatic treatment of vertigo. It is estimated from sales information that >130 million patients have been exposed to the drug since its registration in 1968. In this review we analyse the safety profile of betahistine based on data obtained during >35 years of worldwide postmarketing surveillance. Until 31 December 2005, 554 adverse drug reaction (ADR) reports with 994 individual signs and symptoms were received by the marketing authorisation holder from worldwide sources and were reviewed and evaluated. Signs and symptoms of cutaneous hypersensitivity reactions during betahistine therapy were the most frequently reported complaints. They consisted of usually mild and self-limiting rash, pruritus and urticaria, and all symptoms were reversible after drug discontinuation. Betahistine was reported to be involved in one anaphylactoid reaction and one case of Stevens-Johnson syndrome. Anaphylactic reactions with fatal outcome were not reported. The reports that describe gastrointestinal complaints mostly concern nausea and vomiting or unspecific abdominal pain. These were typically non-serious complaints. Hepatobiliary involvement was reported 25 times, including increases in alkaline phosphatase, gamma-glutamyltransferase, and alanine and aspartate aminotransferase levels. None of the patients concerned developed severe liver failure or died. ADRs related to the nervous system predominantly reveal heterogeneous events that are not suggestive of a specific adverse reaction profile for betahistine. A clinical intolerance to betahistine that gave rise to asthma or bronchospasm was only reported in eight ADRs. A total of three cases of neoplasm have been reported. One case concerned a male patient of unknown age who experienced weight loss, insomnia, impatience and irritability soon after the start of betahistine therapy. An undiagnosed phaeochromocytoma was suspected. The remaining two cases were assessed as being unrelated to betahistine by the reporter. Finally, four deaths have been reported during the course of postmarketing surveillance for betahistine. The reporter assessed the causal relationship to betahistine in two as unrelated, in one as unlikely and the other as unassessable. In summary, clinical and postmarketing studies have revealed a good safety profile of betahistine that was confirmed by the safety surveillance data presented.     

Morphometric analysis of murine skin wound healing: Standardization of experimental procedures and impact of an advanced multitissue array technique

Morphometric data based on skin wounding offer important information for the characterization of the phenotype of transgenic mouse models. The goal of this study was the comparison of technical procedures concerning wounding, processing, and evaluation of samples in different mouse strains. The multitissue array technique was used to estimate its adaptability for standardized analysis in wound healing. Skin wounds between days 1 and 14 after wounding were analyzed. The influence of mouse strain (C57BI/6 vs. FVB/N mice), sex, size of the punch biopsies, and preparation of the tissue sections was investigated on 94 mice. The parameters distance between the migration tongues (deltaMT) and surface not covered by epithelium were evaluated to describe the reepithelialization, and the distance between the adnexa was chosen to measure wound contraction. In addition, the techniques to measure the area of granulation tissue (GT) were evaluated. The data illustrate the requirement of standardized conditions for skin wound-healing experiments and demonstrate that histological preparation in serial sections is mandatory to detect slight differences in wound contraction. For the analysis of cellular composition in GT, multitissue arrays are useful tools in wound-healing studies.