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.     

Spectrometric investigations in ocular hypertension and early stages of primary open angle glaucoma and of low tension glaucoma — multisubstance analysis

The approximation of logarithmic difference spectra between the reflectance of the normal fundus and the fundus reflectance in different stages of glaucoma is demonstrated by a model. The influences of fundus pigments like oxihemoglobin, melanin, xanthophyll and rhodopsin as well as the intensity and the exponent of the scattered light are optimized. Glaucomatous alterations in the extinction of these pigments and of the scattering parameters are different in the macula, in the papillo-macular bundle and in the parapapillary region temporal to the optic disc. A lack of oxihemoglobin only in the papillo-macular bundle in first relative losses in the visual field function points to a damaged microcirculation in early POAG. In progressive glaucoma the extinction spectrum of xanthophyll is detectable in the papillo-macular bundle. A decreased intensity of the scattered light and an altered scattering exponent are suggestive of a damage in the nerve fiber layer at early stages of glaucoma.     

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.     

Oxytocin attenuates amygdala responses to emotional faces regardless of valence.

BACKGROUND: Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS: In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS: Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS: Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.     

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.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Cervical metastases of microcystic adnexal carcinoma in an otherwise healthy woman

Microcystic adnexal carcinoma is a rare cutaneous neoplasm characterized by slow but locally aggressive growth, which normally does not lead to systemic metastasis. Frequent local recurrences are reported, which are most likely due to insufficient operative technique. We present the fourth case of cervical ipsilateral metastatic microcystic adnexal carcinoma in an otherwise healthy woman. The patient presented with a previously diagnosed but not completely resected microcystic adnexal carcinoma in the area of the right posterior scalp and two palpable ipsilateral lymph nodes. The tumor was resected using intraoperative snap frozen histological evaluation of the resection borders. In the same procedure two lymph nodes were resected from the right neck. The lymph nodes were histologically assessed and showed infiltration by small strains of tumor cells. After exclusion of a second primary tumor, e.g., mammary carcinoma, as the cause for cervical lymph node metastases, we performed a modified radical neck dissection with resection of the sternocleidomastoid muscle and the accessory nerve, which was histologically proven to be perineurally infiltrated by tumor cells. In this second procedure the histological evaluation of the specimen showed no sign of remaining tumor infiltration. After exclusion of distant metastasis the patient was irradiated with 60 Gy. The patient is well 1 year after the initial treatment without signs of recurrence.