Possible role of epicardial left ventricular programmed stimulation in Brugada syndrome.

A patient with recurrent syncope due to polymorphic ventricular tachycardia was diagnosed with Brugada syndrome. Programmed right ventricular stimulation could not induce arrhythmia. Epicardial stimulation from a left ventricular site through the coronary sinus led to polymorphic VT. The stimulation protocol for risk stratification in Brugada syndrome is discussed.

Localization of organ of Corti protein II in the adult and developing gerbil cochlea.

The distribution of organ of Corti protein II (OCP-II) was assessed in the developing and mature gerbil cochlea by light and electron microscopic immunohistochemistry. In the adult cochlea, OCP-II was expressed only in certain epithelial cells which included all supporting cells of the organ of Corti, inner and outer sulcus cells and interdental cells. Inner and outer hair cells lacked immunoreactivity. The highest gold particle labeling density was seen overlying intracellular regions devoid of organelles. In the developing inner ear, OCP-II was first detected at 2 days after birth (DAB) with the strongest staining in immature Deiters, inner phalangeal and pillar cells. Immunostaining intensity increased gradually in cells lying laterally and medially to the more centrally located supporting cells and reached adult levels in all reactive cell types around 18 DAB. The results demonstrated conclusively that OCP-II is a cytosolic protein and fail to support its role as a transcription factor postulated on the basis of its homology with p15 or a role in the control of the cycle as suggested by its near-identity with p19Skp1, a cyclin A/CDK2-associated protein. The continued high level of expression in the mature cochlea argues against OCP-II's involvement in regulating the development and differentiation of epithelial cells. The protein's unique distribution and its gradual increase in expression prior to and during the onset and maturation of hearing, however, support its potential function in the recycling of K+ effluxed from hair cells and neurons back to endolymph.

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Identification and cloning of site C splice variants of plasma membrane Ca-ATPase in the gerbil cochlea.

Plasma membrane Ca-ATPase (PMCA) gene products were identified in the gerbil cochlea by reverse-transcription polymerase chain reaction (RT-PCR). Cochlear cDNA was amplified using PMCA isoform-specific primers from splice site C, the calmodulin binding domain. PCR products were cloned and sequenced. The putative housekeeping PMCA genes, 1b and 4b, as expected, were present in the gerbil cochlea and shared 98.6 and 100% amino acid homology with published rat sequences, at splice site C, respectively. PMCA2b, 3a and 3b splice variants also were detected in cochlear cDNAs and shared 95, 94.3 and 98% amino acid homology with their rat counterparts. PMCA isoforms 2 and 3 have been shown to occur in highly specialized tissues, such as muscle and brain, that require finely tuned regulation of intracellular free Ca2+ levels. The presence of several isoforms and splice variants of PMCA in the cochlea most probably reflects their differential expression among the several cell types that have been shown to contain immunoreactive PMCA. This suggests that the cochlea has developed complex mechanisms that finely tune intracellular Ca2+ levels in different highly specialized cell types.

The fine structure of spiral ligament cells relates to ion return to the stria and varies with place-frequency.

Ultrastructural analysis of cells in the cochlea's lateral wall was undertaken to investigate morophologic features relevant to the route of K+ cycling from organ of Corti (OC) to stria vascularis (StV) and to the question of a transcellular versus an extracellular path. The fine structure of outer sulcus cells (OSCs) evidenced their capacity for uptake of K+ from Claudius cells and from perilymph in inferior spiral ligament. Plasmalemmal amplification and mitochondrial density together with known content of Na,K-ATPase testified to activity of type II, IV and V fibrocytes in resorbing K+. Location and fine structure afforded a basis for distinguishing subtypes among the type I, II and IV cells. The type II, IV and V fibrocytes can be viewed as drawing K+ from surrounding perilymph and from OSCs and generating an intracellular downhill diffusion gradient for K+ flow through gap junctions to subtype Ib and Ia fibrocytes and strial basal cells. Pumping action enabled by extreme structural specialization of type II fibrocytes is considered to mediate K+ translocation across the interruption between the gap junction connected epithelial and gap junction connected fibrocyte systems and to explain ion flow directed toward StV through OSCs and fibrocytes despite their lack of polarity. The OSC bodies shrank, their root bundles expanded and the gap junction contact between OSCs and Claudius cells increased toward the base of the cochlea. Expanding root bundles and type I and IIb fibrocyte populations contrasted with shrinking OHCs and Deiters and tectal cells from the apex to the base of the cochlea. These differences indicated an increased magnitude and alternate route of K+ transport toward the StV in high as compared to low-frequency regions. The augmented K+ transport through spiral ligament in basal cochlea correlates with and provides a possible basis for the larger endocochlear potential in the base. The findings appear consistent with current flow extracellularly through scalae tympani and vestibuli and transcellularly through OC, OSCs and class I, II, IV and V fibrocytes.

Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during neoadjuvant chemotherapy.

OBJECTIVE: A clinical study was performed to assess the diagnostic value of spiral CT for evaluation of response during neoadjuvant chemotherapy (CTx) in patients with adenocarcinoma of the gastro-esophageal-junction (GEJ). Results were compared to those of endoscopy. METHODS AND MATERIAL: Twenty-five patients with histologically proven adenocarcinoma of the GEJ scheduled to undergo neoadjuvant CTx were studied. Before CT examination, 1200 ml of a vanilla flavoured paraffin emulsion were applied orally to the fasting patients and 40 mg BuscopanR or 2 mg glucagon were injected i.v. for hypotonia. Iodine (100 ml) was injected automatically (3 ml/s) and the CT scan was started 10 s after complete administration of CM. For response evaluation to CTx, four standardized parameters were measured by two experienced, blinded radiologists. The results were categorized according to the WHO classification of 1981 and compared to those of endoscopy. RESULTS: In 24 of 25 patients endoscopic and computed tomographic response evaluation showed a close correlation (r = 0.96). CONCLUSION: Spiral CT with negative oral contrast agent is a suitable technique for monitoring of GEJ masses. In combination with standardized metric parameters it offers a quantitative response evaluation in patients with GEJ masses during neoadjuvant CTx.

Differences along the place-frequency map in the structure of supporting cells in the gerbil cochlea.

The function of supporting cells was investigated by comparing their morphologic adaptations at six different places in the gerbil cochlea. The volume of Deiters cells and tectal (cover) cells increased whereas that of Boettcher and Claudius cells decreased from base to apex. Deiters cells in the basal region tuned between 40 and 20 kHz lacked the unique rosette complex seen in regions encoding frequencies at or below 10 kHz. Deiters cells in high frequency regions differed from those at lower frequency places in several other ways: they possessed more apical microtubules, a larger basal microtubule stalk, mitochondria in the basal compartment, apical mitochondria that were unassociated with plasmalemma and more symmetric, and a less elaborately folded apicomedial plasmalemma enveloping fewer nerves. The tectal cells covering the outer tunnel appeared unlike Hensen cells in location and structure and differed further in exhibiting more variability with position in the cochlea. These covering cells in regions encoding high frequencies (20 and 40 kHz) extended a thin process medially that formed the roof of the outer tunnel and connected with the phalanx of the third Deiters cell. The tectal cells exclusively in places at 10 kHz or below projected numerous fimbriae into the outer tunnel. Hensen cells lateral to the cover cells also differed with frequency in showing abundant apical microvilli and mitochondria and basal juxtaposition to Boettcher cells only in the 40 to 20 kHz region. The observed structural differences provide evidence for functional variability along the place-frequency map. They attest to greater ion resorption from the outer tunnel by Deiters and tectal cells in low to mid frequency regions, and for greater ion exchange between endolymph and perilymph by Hensen, Boettcher and outer sulcus cells in regions of the cochlea encoding high frequencies. Amplification of the Deiters cells' microtubule system in the base of the cochlea possibly imparts increased stiffness to these cells and enhances transmission of mechanical energy at high frequency.

Patients with anti-Vel--immunohematological characterization and transfusion management.

As reported by other authors we can confirm that the frequency of the blood group Vel negative in Lower Saxony is 1:4000. We report on a patient whose serological characteristics (IgM- and IgA-anti-Vel) made the transfusion of Vel positive blood impossible. Since it was not possible to obtain sufficient Vel negative red cell units in time, the patient was convinced to donate blood for autologous transfusions. This should be the procedure of first choice in the transfusion management of such patients.

GABAergic neurons of rodent brain correspond partially with those staining for glycoconjugate with terminal N-acetylgalactosamine.

Sections of fixed, paraffin-embedded brain from mice and rats were stained with agglutinin from Vicia villosa conjugated to horseradish peroxidase (VVA-HRP) to localize glycoconjugate containing terminal N-acetylgalactosamine (GalNAc). VVA-HRP binding sites were localized in periodic foci at the surface of a selective population of non-pyramidal interneurons in layers II through IV of the rodent cerebral cortex. These multipolar interneurons were shown to utilize gamma-aminobutyric acid (GABA) as a transmitter and thus to be GABAergic by their immunostaining for glutamic acid decarboxylase (GAD) throughout the cytoplasm in serial sections. Pyramidal and other non-pyramidal cortical neurons received GABAergic input as evidenced by punctate immunostaining for GAD on their soma and proximal dendritic arborizations, but these cells failed to show VVA affinity or cytosolic GAD reactivity. Most neurons in the thalamic reticular nucleus stained for the presence of glycoconjugate with terminal GalNAc on their surface and for GAD in the cytosol. In contrast, cerebellar Purkinje cells showed strong cytosolic reactivity with anti-GAD but lacked surface staining with VVA-HRP. These observations show that some but not other populations of GABAergic neurons possess binding capacity for VVA on their surface. The surface of neurons in the deep cerebellar nucleus stained heavily with VVA but failed to show clear cytosolic reactivity for GAD. Some neurons with surface glycoconjugate containing terminal GalNAc are therefore not GABAergic.

D-penicillamine in Wilson's disease presenting as acute liver failure with hemolysis.

Wilson's disease in a young woman presenting with an acute course is described. The clinical manifestations were fulminant hepatic failure associated with marked intravascular hemolysis. Immediate D-penicillamine and high-dose steroid therapy did not influence the course of the disease. Necropsy revealed an increased hepatic copper content and cirrhosis with extensive necrosis of the liver.