Multicenter Randomized Comparison of Xenon and Isoflurane on Left Ventricular Function in Patients Undergoing Elective Surgery

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane.

Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography.

Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon.     

Lessons to be learned from a complicated case of rhino-cerebral mucormycosis in a renal allograft recipient

Fungal infections still represent a serious complication after organ transplantation. Early diagnosis and aggressive treatment are crucial. Because of the many diagnostic problems involved, we present a case of mucormycosis--primarily affecting the paranasal sinuses with later intracranial extension--in a highly immunized recipient of a third renal transplant. Although fungal infection was suspected from various imaging techniques, only the detection of typical fungal hyphae in the infected tissue was diagnostic. Neither the blood tests and cerebrospinal fluid examinations performed nor cultures from maxillary sinus fluid were of any diagnostic help. Surgical debridement from a transnasal as well as an intracranial approach and systemic amphotericin B together with the discontinuation of immunosuppression after removal of the rejected graft were able to save the patient. This case stresses the importance of early diagnosis that can only be made from tissue biopsies and allows appropriate timely treatment.     

Antimycobacterial antihistaminics

The testing of antihistaminic compounds of various chemical classes for antimycobacterial properties is described. A lot of these compounds inhibit the growth of mycobacteria at a concentration of 8-32 micrograms/ml.     

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.     

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.     

DFNA54, a third locus for low-frequency hearing loss

Nonsyndromic hereditary hearing impairment (NSHHI) is a highly heterogeneous disorder with more than 90 loci mapped, of which nearly one-half of the responsible genes are identified. In dominant NSSHI hearing loss is typically biased towards the high frequencies while low-frequency hearing loss is unusual. Only two NSHHI loci, DFNA1 and DFNA6/14/38, are associated with predominantly low- frequency loss. We mapped the loci harboring the gene responsible for autosomal dominant low-frequency hearing loss in a multigenerational family. The pedigree of a Swiss family with low-frequency hearing loss was established. Using genomic DNA, DFNA1 and DFNA6/14/38 were excluded by linkage analysis or by direct sequencing of the responsible gene. Genome-wide linkage analysis was performed using commercially available microsatellite markers. Two-point linkage analysis demonstrated linkage to chromosome 5q31, the locus for DFNA15, with a lod score of 6.32 at recombination fraction =0 for marker D5S436. Critical recombinations were seen at markers D5S1972 and D5S410. Sequencing of the corresponding gene POU4F3 yielded no pathogenic mutation segregating with the affected members. In addition to Wolfram syndrome gene 1 (DFNA6/14/38) and diaphanous (DFNA1) there is evidence for a third gene involved in low-frequency hearing loss located at DFNA15. Because of the differences in auditory phenotype and the absence of pathogenic mutation in the coding region of POU4F3 it is likely that there is a second gene in 5q31, designated DFNA54, associated with NSHHI.     

Sodium and calcium currents shape action potentials in immature mouse inner hair cells

Before the onset of hearing at postnatal day 12, mouse inner hair cells (IHCs) produce spontaneous and evoked action potentials. These spikes are likely to induce neurotransmitter release onto auditory nerve fibres. Since immature IHCs express both α1D (Ca_v1.3) Ca²⁺ and Na⁺ currents that activate near the resting potential, we examined whether these two conductances are involved in shaping the action potentials. Both had extremely rapid activation kinetics, followed by fast and complete voltage-dependent inactivation for the Na⁺ current, and slower, partially Ca²⁺-dependent inactivation for the Ca²⁺ current. Only the Ca²⁺ current is necessary for spontaneous and induced action potentials, and 29 % of cells lacked a Na⁺ current. The Na⁺ current does, however, shorten the time to reach the action-potential threshold, whereas the Ca²⁺ current is mainly involved, together with the K⁺ currents, in determining the speed and size of the spikes. Both currents increased in size up to the end of the first postnatal week. After this, the Ca²⁺ current reduced to about 30 % of its maximum size and persisted in mature IHCs. The Na⁺ current was downregulated around the onset of hearing, when the spiking is also known to disappear. Although the Na⁺ current was observed as early as embryonic day 16.5, its role in action-potential generation was only evident from just after birth, when the resting membrane potential became sufficiently negative to remove a sizeable fraction of the inactivation (half inactivation was at −71 mV). The size of both currents was positively correlated with the developmental change in action-potential frequency.     

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.