[Possibilities for preserving hearing in labyrinth fistulas of different degrees of severity]. / Möglichkeiten des Hörerhalts bei Labyrinth-Fisteln von unterschiedlichem Schweregrad.

The labyrinthine fistula continues to be one of the most common complications in ears with cholesteatoma. Fifty-one patients with labyrinthine fistula were identified in a series of 1243 cases with cholesteatoma operated upon between 1989 and 1993 at the University ENT Clinic Wuerzburg. The surgical management concept comprised of removing the cholesteatoma matrix, categorizing the fistula type, and immediate covering of the labyrinthine capsule defect with bone dust, perichondrium and fibrin glue. The classification system of the fistulae used in the study used the depth of labyrinthine involvement as a criterion and also took into account the possibility of intentional or accidental damage to the labyrinth during surgical manipulation (Fig. 1). From 1991 on, patients were treated with 500 mg of Presnisolon 21 hydrogen succinate in a single intravenous dose, at the time the fistula was corrected. The postoperative hearing results were graded based on the extend of preservation of inner ear function at or near the preoperative level. None of the patients who had corticosteroid therapy suffered a profound sensory neural hearing loss (Fig. 2, 3), whereas five ears without steroids and a deep fistula lost function completely. The study concluded that corticosteroids have a beneficial impact on postoperative outcome in cases with severe injury to the membranous labyrinth.

Genetic variation in lipoprotein (a) levels in families enriched for coronary artery disease is determined almost entirely by the apolipoprotein (a) gene locus.

Lipoprotein (a) (Lp[a]) is a cholesterol-rich lipoprotein resembling LDL but also containing a large polypeptide designated apolipoprotein (a) (apo[a]). Its levels are highly variable among individuals and, in a number of studies, are strongly correlated with the risk of coronary artery disease (CAD). In an effort to determine which genes control Lp(a) levels, we have studied 25 multiplex families (comprising 298 members) enriched for CAD. The apo(a) gene was genotyped among the families, using a highly informative pulse-field gel electrophoresis procedure. In addition, polymorphisms of the gene for the other major protein of Lp(a), apolipoprotein B (apoB), were examined. Quantitative sib-pair linkage analysis indicates that apo(a) is the major gene controlling Lp(a) levels in this CAD population (P = .001; 99 sib pairs), whereas the apoB gene demonstrated no significant quantitative linkage effect. We estimate that the apo(a) locus accounts for < or = 98% of variance of Lp(a) serum levels. Approximately 43% of this variation is explained by size polymorphisms within the apo(a) gene. These results indicate that the apo(a) gene is the major determinant of Lp(a) serum levels not only in the general population but also in a high-risk CAD population.

Linkage between the APOB gene and serum ApoB levels in a large pedigree from the Bogalusa Heart Study.

Maximum likelihood linkage analyses were performed to test for linkage between serum apoB levels and several candidate gene markers including apolipoprotein B, lipoprotein lipase, hepatic lipase, cholesterol ester transfer protein, and apolipoprotein AI in a large pedigree. Parameters of general Mendelian inheritance derived from maximum likelihood segregation analysis of the serum apoB levels were used in the linkage analysis. The highest two-point lod score between the quantitative trait and a marker defined by a single restriction digest was 1.86 at recombination fraction (theta) = 0. This was observed for linkage between serum apoB levels and the presence or absence of a PvuII digestion site in the apoB gene. Linkage between serum apoB levels and polymorphisms of the apoB gene defined by the two restriction digests EcoR1 and PvuII was supported by a lod score of 3.30, while inclusion of VNTR typings led to a lod score of 2.33. None of the other candidate genes gave positive evidence of linkage.

Genetic contributions to quantitative lipoprotein traits associated with coronary artery disease: analysis of a large pedigree from the Bogalusa Heart Study.

A pedigree of a large family with high prevalence of heart disease is subjected to association and sib-pair linkage analysis to investigate the role of 5 candidate genes in the regulation of lipoprotein metabolism and the development of coronary artery disease. At the 5% nominal significance level, the apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL-C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly significant association between allele 7 and low triglyceride levels (P = 0.004). No significant linkage results were found with cholesterol ester transfer protein (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and triglyceride levels (P = 0.005). At the 5% nominal significance level, haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or associations. The study thus indicated that genetic variation of APOB, LPL, CETP, and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may play an important role in the regulation of lipoprotein metabolism and could contribute to the risk of coronary artery disease.

Electrical evaluation of the facial nerve in acoustic neuroma patients: preliminary comparison between transcranial magnetic coil stimulation and electroneurography.

Subclinical involvement of the facial nerve by acoustic neuromas may be identified preoperatively using conventional electroneurography (ENoG). The clinical application of extratemporal stimulation distal to the stylomastoid foramen is limited in these cases by the more proximal site of the lesion. Transcranial magnetic coil stimulation (MCS) is a noninvasive means by which the facial nerve is stimulated at the level of the motor cortex or the brain stem, before it enters the internal auditory canal. Topographically such an assessment may have more diagnostic relevance than other forms of electrical stimulation in acoustic neuroma patients. To test this theory the facial nerves of 20 patients with acoustic neuromas were stimulated using ENoG and MCS preoperatively and 1 week postoperatively. Stimulation parameters were comparable and included threshold and suprathreshold levels of stimulation while compound action potential amplitudes and early and late response latencies were monitored. Facial nerve function was assessed clinically using the Stennert grading system. All the patients had clinically normal facial nerve function preoperatively. Normative data suggested a close correlation between threshold and suprathreshold amplitudes generated by both ENoG and MCS. To the contrary, in the pathologic ears there was a higher incidence of stimulus response abnormality determined by MCS than by ENoG. A comparison of these data, tumor size, and postoperative results promotes further evaluation of MCS as a prognostic index in acoustic neuroma patients.

[Electrophysiologic evaluation of the facial nerve in patients with acoustic neuromas. Preliminary results of a comparative study between conventional electroneurography and transcranial magnetic pulse stimulation]. / Elektrophysiologische Beurteilung des Nervus facialis bei Patienten mit Akustikusneurinomen. Vorläufige Ergebnisse einer vergleichenden Untersuchung zwischen konventioneller Elektroneurographie und transkranieller Magnetspulenstimulation.

Subclinical invasion of the facial nerve by acoustic neuromas may be identified preoperatively using conventional electroneurography (ENOG). The clinical application of extratemporal stimulation distal to the stylomastoid foramen is limited in these cases because of the more proximal site of the lesion. Transcranial magnetic coil stimulation (MCS) is a non-invasive means by which the facial nerve is stimulated at the level of the motor cortex or the brain stem before it enters the internal auditory canal. Topographically such an assessment may have more diagnostic relevance than other forms of electrical stimulation in acoustic neuroma patients. To test this theory the facial nerves of 20 patients with an acoustic neuroma were stimulated using ENOG and MCS before and 1 week after operation. Stimulation parameters were comparable and included threshold, double-threshold and supra-threshold levels of stimulation while compound action potential amplitudes and early and late response latencies were monitored. All the patients had clinically normal facial nerve function preoperatively. Using ENOG 65% of the patients showed amplitude reduction on the tumour side, whereas 70% of these patients had a reduction of amplitude to MCS. Combining both techniques, 88% of the patients had a significant amplitude reduction on the neuroma side. Comparison of the preoperative threshold measurements of both techniques showed that there was a significantly higher incidence of detection of lesions on the diseased side in neuromas larger than 2 cm by the use of MCS.

Late potentials and ejection fraction at hospital discharge: prognostic value in thrombolyzed and non-thrombolyzed patients. A preliminary report. The Belgian Working Group for Signal Averaging.

The prognostic value of the use of thrombolytic therapy (TL), the ejection fraction (EF) and the presence of late potentials (LP) in the signal-averaged ECG (filter less than 40 Hz) at the time of hospital discharge was assessed in a multicenter prospective study. This report presents the follow-up at 4 months of the first 263 patients. Thrombolytic therapy was given to 41%. The mean ejection fraction was 45%. The average duration of the high frequency QRS complex (HFQRS) was 104 ms. The mean duration of the terminal signal under 40 microV (D40) was 31 ms. The combination of both HFQRS greater than 110 ms and a D40 greater than 40 ms was considered as presence of LP. The cardiac mortality at 4 months was 5.7% (15 patients). Late ventricular tachycardia or fibrillation occurred in 2.3% (6 patients). The relative risk (RR) for cardiac death or late events was 5.14 with a 95% confidence interval (CI) of 1.2 to 22.0 when no thrombolytic therapy was used. The RR was 3.39 (CI: 1.4 to 8.4) for patients with an EF lower than 30%. The single most important electrocardiographic parameter was a D40 greater than 40 ms (RR: 3.14, CI: 1.3 to 7.8). The presence of LP had a RR of 4.28 (CI: 1.7 to 10.5). With stepwise regression analysis it was evident that cardiac function and information obtained by signal averaging offered independent prognostic information. The presence of LP at hospital discharge after acute infarction offers additional prognostic information to EF for the risk of later cardiac death, especially in patients without thrombolysis.

Inhibition of phosphoinositide metabolism in human polymorphonuclear leukocytes by S-adenosylhomocysteine.

Transmembrane signaling by chemoattractants in leukocytes appears to require activation of phosphoinositide metabolism with subsequent generation of the second messenger substances, inositol(1,4,5)trisphosphate and diacylglycerol. In addition, previous studies have shown that conditions which lead to an intracellular increase in S-adenosylhomocysteine (AdoHcy), a by-product and competitive inhibitor of S-adenosylmethionine-mediated methylation reactions, inhibit all chemoattractant-mediated functions of leukocytes, suggesting that AdoHcy also interferes with chemoattractant transmembrane signaling. In the present study, we determined whether AdoHcy altered the metabolism of phosphoinositides in human polymorphonuclear leukocytes. Treatment of 32P-labeled polymorphonuclear leukocytes with the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, plus exogenous adenosine and L-homocysteine thiolactone, conditions which cause an increase in AdoHcy, produced as much as a 37% decrease in the amount of [32P]phosphatidylinositol 4-monophosphate associated with the cells. The formation of inositol bisphosphate was inhibited by as much as 45% by erythro-9-(2-hydroxy-3-nonyl)adenine, adenosine, and L-homocysteine thiolactone suggesting decreased availability of phosphatidylinositol 4-monophosphate. In support of this, AdoHcy, in concentrations ranging from 0.01 to 0.1 mM, inhibited the transfer of gamma-32P from gamma-[32P] ATP to phosphatidylinositol (PtdIns). The inhibition of PtdIns kinase was competitive with an apparent Ki for AdoHcy of 43 microM. Increased intracellular AdoHcy reduced chemoattractant-mediated increases in inositol(1,4,5)trisphosphate formation suggesting abrogation of transmembrane signaling. These findings for the first time demonstrate that AdoHcy is a competitive inhibitor of PtdIns kinase and thus a regulator of the phosphoinositide pathway.