Effect of maternal administration of thyrotropin-releasing hormone or DN1417 on functional and morphologic fetal rabbit lung maturation and duration of survival after premature delivery

Though maternal treatment with thyrotropin-releasing hormone (TRH) for prevention of hyaline membrane disease has been utilized, precise mechanisms of TRH in accelerating fetal lung maturation remain unclear. We studied the effect of maternally administered TRH or DN1417 (an analog of TRH) on functional and morphologic fetal rabbit lung maturation and the duration of survival after premature delivery. Because DN1417 retains the neurotransmitter but not the neuroendocrine effects of TRH, this study enables us to determine which of these effects was responsible for enhancement of lung maturation. TRH or DN1417 (0.2 mg/kg/dose) or saline was injected intravenously into New Zealand White rabbit does 48, 36, 24, 12 and 2 h prior to sacrifice on day 27 of gestation. Functional pulmonary maturity was assessed by pressure-volume hysteresis, and morphologic maturity was assessed by histologic technique. Maternal administration of TRH or DN1417 enhanced both functional and morphologic fetal lung maturation as well as the duration of neonatal survival after premature delivery. We propose that the effect of TRH in fetal lung maturation is due to neurotransmitter rather than neuroendocrine effects.     

Agenesis of the Gallbladder Revisited Laparoscopically

Gallbladder agenesis is an extremely rare disease. Necropsy incidence has been reported to be 0.016%. Failure lo locate the gallbladder at the time of a planned cholecystectomy can be very challenging. We report such a case during a laparoscopic cholecystectomy. The indication for surgery in these patients are complaints of gallbladder symptoms along with a false-positive ultrasound study. During exploration, an abnormal location of the gallbladder has to be excluded. Ectopic gallbladder locations include intrahepatic, lesser omentum, retroperitoneal, retrohepatic, within the falciform ligament, retroduodenal, and retrohepatic areas. Thorough exploration and cholangiography are essential. Embryologically, the gallbladder and cystic duct arise from the caudal portion of the hepatic bud. All of the previously reported cases of gallbladder agenesis have shown an absence of both the gallbladder and cystic duct. We report an embryological oddity wherein a patent cystic duct was found along with an agenetic gallbladder. This is the first case report of this finding, along with this being the first absent gallbladder discovered laparoscopically.     

INCREASED RATE OF ETHANOL ELIMINATION AND ELEVATED BLOOD ACETATE IN ASTHMATICS ON CORTICOSTEROID, BETA-2-SYMPATHICOMIMETIC AND THEOPHYLLINE TREATMENT

The rate of ethanol elimination and blood acetate concentrationsafter a peroral dose of alcohol were measured in eight asthmaticpatients receiving high-dose corticosteroid, sustained releasetheophylline and beta-2-sympathicomimetic treatment and in eightnonalcoholic, healthy controls. Mean ethanol elimination rate(ER) and mean blood acetate concentration (AC) were significantly(P<0.01) higher in asthmatics (ER=134.8 ± 12.9 mg/kg/hr,AC = 1.13± 0.25 mM) than in controls (ER = 100.2 ±12.3 mg/kg/hr, AC = 0.64 ± 0.10 mM). In the asthmaticsthere was a significant negative correlation between the ageand the rate of ethanol elimination (r = –0.890, P <0.01); in the control group, however, this correlation was oflower degree (r = –0.423) and did not achieve statisticalsignificance. Enhanced ethanol metabolism in asthmatics is possiblydue to the effect of drugs. Our results suggest that ethanolelimination rate is increased in asthmatics receiving medicationand that the effect is most significant in younger age groups.     

Studies on Propafenone-type Modulators of Multidrug-Resistance IV: Synthesis and Pharmacological Activity of 5-Hydroxy and 5-Benzyloxy Derivatives

A series of 5-hydroxy and 5-benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR-modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3 . Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d . Subsequent cleavage of the benzyl group gave the 5-hydroxy analogs 6a–d . Structure activity relationship studies showed, that the 5-hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5-benzyloxy analogs 5a–d showed almost identical EC₅₀ values, independent of their log P value.     

Stereoselectivity of actions of the calcium sensitizer [+]-EMD 60263 and its enantiomer [-]-EMD 60264

The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca²⁺-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca²⁺-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC₅₀ of Ca²⁺ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to 113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component I_Kr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define I_Kr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca²⁺-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the I_Kr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions are clearly independent of sterical configuration. The combination of Ca²⁺-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic use. Received: 7 January 1997 / Accepted: 25 February 1997     

Herzoperationen wegen Herztumoren in Deutschland – Ergebnisse eienr Umfrage für das Jahr 1996

Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor. Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik Deutschland ein standardisierter Fragebogen zugesandt. Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie, Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel einer Operation zugeführt. Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich weit überwiegend um Myxome handelt. Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998     

Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion.

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.