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.     

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     

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 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     

Value of contrast-enhanced MRI of breast after silicone implant

Summary Early recognition of recurrence and work-up of clinically indeterminate lesions may be impaired after reconstruction with silicone implants due to superimposition of the implant or to scarring. This study was undertaken to evaluate the use of contrast-enhanced MRI in patients with silicone implant after breast cancer. Contrast-enhanded MRI was offered to 169 patients. Comparative two- to three-view mammography was also performed in 169 patients, as well as comparative sonography in 144 patients. Conventional imaging and clinical examination detected only 8/13 recurrences, whereas 12/13 were detected by MRI. One recurrence had been visible as a strongly enhancing 2-mm dot in a previous examination (2 years before), but was not called. It was therefore counted as false negative. In addition, multicentricity was detected by MRI alone in two of three cases. MRI correctly diagnosed scar tissue in all cases with indeterminate findings. However, due to false-positive calls caused by enhancing granulomas specificity could not be improved. Contrast-enhanded MRI allowed decisive additional information in our study group and improved the sensitivity significantly (concerning all diagnoses). Contrast-enhanded MRI is recommended in patients with diagnostic problems or high risk of recurrence after silicone implants.      

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.     

Formoterol, a new long acting beta 2 agonist for inhalation twice daily, compared with salbutamol in the treatment of asthma.

Sixteen patients with stable chronic asthma participated in a double blind crossover study comparing the new inhaled long acting beta 2 agonist formoterol with salbutamol. Inhaled (n = 15) and oral steroid (n = 1) treatment were maintained at the same daily dose throughout the study. For four weeks the patients received either formoterol 24 micrograms twice daily or salbutamol 400 micrograms twice daily, plus additional puffs (with the same drug) when needed. Asthma symptoms, additional puffs of beta 2 agonist, peak expiratory flow (PEF), and side effects were recorded daily. During treatment with formoterol the patients used fewer additional puffs of beta 2 agonist, had better symptom scores, less disturbed sleep, more days without additional aerosol, and higher PEF both morning and evening than during salbutamol treatment. Thus formoterol 24 micrograms twice daily gave long lasting bronchodilatation and asthma symptoms were well controlled with regular twice daily administration.     

Clinical characteristics and surgical treatment of sporadic primary hyperparathyroidism with emphasis on chief cell hyperplasia

In 570 patients with sporadic primary hyperparathyroidism, the age, sex, symptoms, and preoperative serum calcium values were related to the histopathologic diagnoses, operative findings, and the extent and outcome of parathyroid surgery. Renal stone formation was especially prevalent in younger patients with slight hypercalcemia and parathyroid chief cell hyperplasia, whereas neuromuscular and psychiatric disturbances were overrepresented among older women with higher serum calcium values. Serum calcium concentration was inversely correlated to the proportional incidence of chief cell hyperplasia and positively correlated to the glandular weight of both adenomas and hyperplasias. Glandular size was markedly irregular in chief cell hyperplasia, with increased gland weights of no more than two glands in 78% of patients. During follow-up, for as long as 27 years, normocalcemia was obtained in 91% of patients with adenomas, with failures mainly depending on difficulties in identifying the parathyroid glands. The rate of normocalcemia was lower (80%) among patients with hyperplasia, but an inability to visualize the glands was not a major cause of failure. In patients with hyperplasia with asymmetric and more markedly enlarged glands, it appeared sufficient to remove only the enlarged glands, whereas the findings advocated a subtotal 3- to 3.5-gland resection in patients with more symmetrically or less enlarged hyperplastic glands.     

Krankheitsprognose,psychosoziale Belastung und Einstellung von Melanompatienten zu unterstützenden psychotherapeutischen Maßnahmen

Zusammenfassung Bei 205 Melanompatienten im Stadium I und II wurden das Ausma? der psychosozialen Belastung und der sozialen Unterstützung sowie die Einstellung der Patienten zu unterstützenden Gespr?chsangeboten erhoben. 59% der Patienten fanden zus?tzliche unterstützende Gespr?che mit dem behandelnden Dermatologen, 20% mit einem Psychotherapeuten sinnvoll. Patienten, die starke Angst vor einem Fortschreiten des Tumors ?u?erten und die sich über die Erkrankung nicht ausreichend aufgekl?rt fühlten, wünschten Gespr?che mit dem behandelnden Arzt. Patienten, die sich psychosozial st?rker belastet fühlten und sozial weniger Unterstützung durch ihr soziales Umfeld angaben, befürworteten Unterstützung durch einen Psychotherapeuten. Auch eine ungünstige Prognose scheint das Interesse an psychotherapeutischer Unterstützung zu verst?rken. Eingegangen am 13. Januar 1995 Angenommen am 23. August 1995