Breakdown of the round window membrane permeability barrier evoked by streptolysin O: possible etiologic role in development of sensorineural hearing loss in acute otitis media.

Sensorineural hearing loss is a common sequela of acute and chronic otitis media, and the round window membrane (RWM) is currently being considered as a major route for noxious agents to pass from the middle ear cavity to the cochlea. Streptococcus pneumoniae, a major causative agent of otitis media, and Streptococcus pyogenes A produce molecularly related toxins, pneumolysin and streptolysin O (SLO), that form large pores in target membranes. In this study, we analyzed the effects of SLO on the permeability of the RWM. Resected RWMs from a total of 104 guinea pigs were embedded between two chambers of an in vitro system. One chamber was designated as the tympanal (cis) compartment, and the other was designated as the inner ear (trans) compartment. The permeability of normal and SLO-damaged RWMs towards Na+, [14C]mannitol, and proteins was investigated. SLO evoked permeability defects dose dependently in the RWM with fluxes of both Na+ and [14C]mannitol being demonstrable over a time span of up to 8 h. Serum proteins and radioiodinated SLO were also shown to pass through the damage RWM. Scanning electron microscopy revealed the morphological correlates to these results. We propose that damage to the RWM by potent pore-forming cytolysins leads to leakage of ions from the perilymph. Ionic disequilibrium and passage of noxious macromolecules to the cochlea could contribute to disturbances of the inner ear function.     

Antibodies to nucleic acids in myasthenia gravis.

An increased frequency of antibodies to native DNA, thymocytes, and striated muscle was found in patients with myasthenia gravis (MG). The prevalence of such antibodies lends considerable support to the concept of MG as an autoimmune disorder and militates in favor of major abnormalities in the thymic dependent immune system. There was no correlation between serum-blocking activity to acetylcholine receptor protein and antibodies to thymocytes.     

A fourth case of ring chromosome 7

An 8-year-old child with a ring chromosome 7 is presented, the first female and the fourth such individual to be described. The associated anomalies were rather benign: she presented with short stature, minor skeletal alterations, and normal intelligence. The only truly striking feature was the presence of multiple large, pigmented naevi, suggestive of a hamartomatous origin, but unlike those typical of any particular syndrome. Though other ring 7 patients have had naevus flammeus, and one had cafk-au-lait spots, our proband is the first with an anomaly of chromosome 7 to have such extensive lesions. These four cases of ring 7, which show great phenotypic variation, are reviewed, and the clinical presentation of the proband is also compared with that of patients suffering from terminal, interstitial and translocation-derived 7p and 7q deletions. The formation and behaviour of ring chromosomes are discussed, as are the cytogenetic factors which may influence their phenotypic expression.     

Der Tagesgang der Phasenkoppelung zwischen Herzschlag und Atmung in Ruhe und seine Beeinflussung durch dosierte Arbeitsbelastung

Zusammenfassung An insgesamt 33 gesunden Versuchspersonen im Alter von 18–32 Jahren wurde der Tagesgang der Phasenkoppelung zwischen Herzschlag (R-Zacke im EKG) und Atmung (Inspirationsbeginn) mit dem Koincidenzmeßgerät Synchromet unter verschiedenen Bedingungen untersucht. Bei 10 Probanden erfolgten die Messungen bei Bettruhe in einstündigen Abständen, weitere 10 Personen wurden alle 2 Std im Anschluß an die Koppelungsmessung mit dosierter Tretkurbelarbeit belastet, die übrigen 13 Probanden nur in vierstündigen Abständen, wobei die Phasenkoppelung zweistündlich kontrolliert wurde.In der Ruhegruppe fand sich im Mittel ein signifikanter tagesrhythmischer Gang des Koppelungsgrades mit einem nächtlichen Maximum gegen 1.00 Uhr und einem Minimum zwischen 12.00 und 17.00 Uhr. Die individuellen Tagesamplituden des Koppelungsgrades betragen zwischen 2,8 und 11,6 E (Mittelwert 6,4); sie waren um so größer, je höher das individuelle Tagesniveau von Pulsfrequenz und Puls-Atem-Quotient lag. Die individuellen Tagesmaxima lagen in Ruhe zu 85% in der Nachthälfte (19.00-7.00 Uhr), die Minima zu 75% am Tage (7.00-19.00 Uhr).Bei vierstündlich wiederholter Arbeitsbelastung war die Amplitude im mittleren Tagesgang des Koppelungsgrades, der zwei Gipfel mit 12stündigem Abstand aufwies, signifikant kleiner, bei zweistündlicher Belastungsfolge fehlte sie vollständig. Die individuellen Amplitudenwerte betrugen zwischen 1,3 und 7,5 (Mittelwert 3,1) bzw. 1,1 und 5,5 E (Mittelwert 2,8). Die individuellen Tagesmaxima lagen bei vierstündlicher Belastung noch zu 65% in der Nachthälfte, bei zweistündlicher Belastung nur noch zu 60%, die entsprechende Minimahäufigkeit in der Tageshälfte betrug 58 bzw. 50%. Die Häufigkeitsverteilung der Maxima und Minima war vorzugsweise zweigipfelig mit etwa 12stündigen Gipfelabständen.Im Gegensatz zu der Abschwächung bzw. Unterdrückung der nächtlichen Zunahme des Koppelungsgrades näherte sich das mittlere Frequenzverhältnis aus Puls und Atmung auch in den Belastungsgruppen während der Nacht der Norm 41 an. Der mittlere Tagesgang der Herzfrequenz war bei ähnlichem Niveau aller drei Gruppen nur bei vierstündlicher Belastungsfolge deutlich zweigipfelig mit 12stündigem Gipfelabstand.Die tagesrhythmische Schwankung des Koppelungsgrades wird auf vegetative Umstellungen zurückgeführt, die nicht unmittelbar an den Schlaf gebunden sind. Aus den Befunden bei Arbeitsbelastung wird geschlossen, daß die Phasenkoordination zwischen Herzschlag und Atmung schon durch leichte Arbeitsbelastung nach-haltig gestört wird und längere Erholungszeiten benötigt als Frequenz und Frequenzkoordination beider Rhythmen. Die Phasenkoppelung wird daher als empfindlichster Indicator für die Erholungsvorgänge im Bereich der rhythmischen Koordination angesehen.     

Association analysis of a polymorphism in the G‐protein stimulatory α subunit in patients with major depression*

Growing evidence suggests that G‐proteins may be involved in pathogenesis and treatment of affective disorders. Several studies have reported altered levels and/or activities of stimulatory G‐proteins in depression. The aim of this study was to investigate whether a polymorphism in the stimulatory α subunit of G‐proteins (T/C point mutation in exon 5; ATT → ATC at codon 131) is associated with major depression or response to antidepressant treatment. Therefore, we performed a case‐control association study with 212 depressive patients and 137 healthy, unrelated controls. There was no evidence for an association between the investigated polymorphism in the Gα_s gene and major depression, as well as to treatment response. The results of our study are in concordance with recently published findings which do not support the hypothesis that the gene for the stimulatory α subunit of G‐proteins is a major susceptibility factor in the pathophysiology of major depression. © 2002 Wiley‐Liss, Inc.     

Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume.

Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of haematocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6.5% higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of 'silent' ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man.     

A complex translocation in a 5-year-old boy with acute myeloblastic leukemia

A complex translocation [t(2;10;11)(q34;q11;q13)], an extra chromosome #8, and a duplication of 17q were the major findings in blast cells found in the bone marrow of a 5-yr-old boy with AML-M2 both before treatment and during relapse. The child died 8.5 mo after diagnosis, despite intensive combination chemotherapy.     

Thermal pleasantness sensation: an indicator of thermal stress

Summary The degree of pleasantness or unpleasantness of thermal sensation aroused by a particular peripheral thermal stimulus has been shown to be an indicator of thermal state of the body in relation to the thermoregulatory set point. This phenomenon is known as thermal alliesthesia. The quantification of thermal alliesthesia was possible using two methods: (1) A set of temperature stimuli (15, 20, 25, 30, 35, and 38 C) was applied, by means of a Peltier thermode 5.5×2.7 cm², on the back of the hand, the forehead, and the back of the neck. When each stimulus had been applied for 5 s the subjects voted their degree of thermal pleasantness/unpleasantness on a psychophysical scale ranging from +2.0 for very pleasant to –2.0 for very unpleasant. (2) The subjects were also asked to adjust the Peltier thermode temperature, without looking at the temperature scale, such that the temperature (on the back of the neck) was maintained at the level the subjects considered most pleasant. The subjects also rated their general thermal comfort sensation on a five point scale ranging from +2.0 for very comfortable to –2.0 for very uncomfortable. Rectal temperature and skin temperature at eight locations were continuously recorded. Passive thermal exposures (54) were made with nine passive subjects and 42 exposures were done with working (50 watt) subjects. All exposures were carried out in a climatic chamber at a constant temperature, relative humidity (45%), and air speed (0.3 m/s). Each subject underwent 6 exposures at six room temperatures of 15, 20, 25, 30, 35, and 40 C. The results of work exposures confirmed the findings of previous studies; namely, the effect of core temperature change overrides any effect due to mean skin temperature on alliesthesial response. A mathematical function to predict the mean slope of the thermal pleasantness rating/stimulus line (a measure of the alliesthesial response) was derived using the data obtained from the passive thermal exposures. The results indicate that alliesthesial response can be used as a quantitative indicator of thermal stress.Supported by the European Coal and Steel Community, Luxembourg