Non-atopic IgE and eosinophil cationic protein after allogeneic hematopoietic stem cell transplantation in children.

Allogeneic hematopoietic stem cell transplantation (HSCT) in childhood is associated with severe pulmonary complications, but the pathophysiologic mechanisms remain unclear. Our aim was to evaluate the association of total and specific IgE, eosinophil cationic protein (ECP) and eosinophilia in HSCT recipients with pulmonary complications. We prospectively measured total and specific serum IgE, eosinophils, and ECP before and 28, 100, and 180 days after HSCT. We included 30 children (age 2-17 years) undergoing HSCT. Nine patients had a history of previous atopy without being associated with pulmonary complications after HSCT until day +360. Specific IgE levels showed a decline after HSCT, associated with the absence of allergy symptoms, suggesting a reduction of atopy. Elevated total serum IgE levels occurred in seven patients on day +28 after HSCT. This elevation did not coincide with allergy symptoms. ECP showed no correlation with total allergy symptoms, eosinophilia, IgE levels, or pulmonary complications. There was a significant correlation (p = 0.0367) between ECP levels on day +28 and concurrent acute graft-versus-host disease (GvHD). Non-atopic serum ECP and IgE levels are elevated on day +28 after HSCT in children, with ECP showing a potential relation to acute GvHD.

Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation.

UNLABELLED: Pulmonary complications are major causes of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). We hypothesise that elevated exhaled nitric oxide (FeNO) levels early after HSCT in children are predictive for pulmonary complications. The present prospective study included 30 children (age, 4-18 years) before HSCT. FeNO levels were evaluated 10 days before transplant, at day 0, day +28 and day +60 after HSCT. During the follow-up period until day +100, pulmonary complications and lung function were assessed. Before HSCT, the mean FeNO levels were comparable in children with or without post-transplant pulmonary complications. However, they differed at day 0 and day +28 with a mean of 7 (±1.95) and 13 (±3.44) ppb at day 0 and a mean of 13 (±3.44) and 14 (±3.57) ppb at day +28, respectively. CONCLUSION: Children with pulmonary complications after day +28 have higher mean FeNO levels 28 days after HSCT than children without later pulmonary complications. Therefore, FeNO could be an important diagnostic tool for hyperinflammatory response in bronchial epithelium after paediatric HSCT.

The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy.

OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

Novel 3,7-diheterabicyclo[3.3.1]nonanes that possess predominant class III antiarrhythmic activity in 1-4 day post infarction dog models: X-ray diffraction analysis of 3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nona ne dihydroperchlorate.

Several 3,7-diheterabicyclo[3.3.1]nonanes (DHBCNs) were prepared and screened in the Harris dog model for their ability to abolish pace-induced and sustained ventricular tachycardia (SVT) or prevent induction of ventricular tachycardia. In addition, an electrophysiological examination was made in the infarcted hearts of each animal to determine if more than one class activity was present. The examples exhibited predominately class III antiarrhythmic activity via a prolongation of the ventricular effective refractory period (VERP) in the models, although there may well be an underlying class Ib action present as exemplified by the ability of several of the agents to slow conduction in the myocardial infarcted dog hearts. 3-[4-(1H-Imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo[3.3.1]nonan e dihydroperchlorate displayed powerful class III activity in the model systems while several other DHBCNs exhibited various degrees of class III action. An X-ray diffraction analysis revealed that this compound has a 3,7-diazabicyclo[3.3.1]nonane bicyclic unit in a chair-chair conformation.

Hexamethylenebisacetamide (HMBA) is a growth factor for human, ovine and porcine thyroid cells.

Hexamethylenebisacetamide (HMBA) provokes in murine erythroleukemia cells (MELC) a commitment to terminal differentiation leading to the activation of the expression of hemoglobin. HMBA has been tested also in other cells from colon cancer, melanoma or lung cancer. However it has not yet been tested in the thyroid. We demonstrate in this paper that HMBA in kinetics and concentration-response experiments increases the proliferation of human thyroid cells isolated from Graves'-Basedow patients. It also acts like a growth factor for ovine and porcine thyroid cells, respectively, from the OVNIS line and the ATHOS line. This molecule which is a differentiating factor in the MELC system and a growth factor in human thyroid cell cultures represents a potential to get human thyroid cell lines expressing specialized functions.

DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) increases iodide trapping, inhibits thyroperoxidase and antagonizes the TSH-induced apical iodide efflux in porcine thyroid cells.

4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of several anionic channels and transporters including the band 3 protein of the red blood cell membrane was tested on iodide metabolism in cultured porcine thyroid cells. We used three experimental cell culture models: (i) forskolin-stimulated correctly inside-in polarized follicle-associated thyroid cells cultured onto plastic support (ii) suspensions of isolated cells derived from such cultures (iii) polarized monolayers in bicameral chambers. DIDS was observed to increase free-iodide trapping in all conditions. Organification of iodide by follicle-associated cell cultures incubated for 6 h decreased as a function of DIDS concentration with an IC50 of 5 x 10(-5) M. This block in organification is accounted for a block in thyroperoxidase activity as in vitro both purified lactoperoxidase and purified porcine thyroperoxidase were inhibited by DIDS with a similar dose-dependency the IC50 being also of 5 x 10(-5) M. Both control and DIDS-treated cells in suspension, actively trapped iodide and reached a steady concentration in about 50 min; however the plateau was 4.4-fold higher in (10(-3) M) DIDS-treated cells. Acute TSH-stimulation at this plateau of 125I-preloaded cells in suspension in the presence of 2 mM methimazole (MMI) induced a fast release of iodide from these cells as expected (first step of the TSH-biphasic effect). This TSH-induced iodide efflux was however completely inhibited by DIDS (10(-3) M). Furthermore, addition of DIDS to the apical compartment of TSH-prestimulated cell monolayers in bicameral chambers resulted in an increase in intracellular-iodide concentration and in an inhibition of iodide efflux into the apical medium. Taken together, the present results demonstrate that DIDS mainly interacts with two main components of the thyroid apical cell membrane: thyroperoxidase and a cAMP-sensitive iodide channel.

Effect of GLG-V-13, a class III antiarrhythmic agent, on potassium currents in rabbit ventricular myocytes.

The effects of a new Class III antiarrhythmic drug, GLG-V-13, on the 4-aminopyridine sensitive transient outward current, on the inward rectifier potassium current, on the ATP sensitive potassium current and on the rapid and slow components of the delayed rectifier potassium current were studied in single rabbit ventricular myocytes using the whole-cell voltage-clamp technique. GLG-V-13 blocked the rapid component of the delayed rectifier potassium current in a dose-dependent manner, with an estimated EC50 value of 0.36 microM. At high concentration, the slow component of the delayed rectifier potassium current was also depressed by the drug (40% effect at 10 microM concentration). The transient outward current, the inward rectifier potassium current and the ATP sensitive potassium current were not influenced by GLG-V-13, even at 10 microM concentration. Thus, GLG-V-13 blocks predominantly the rapid component of the delayed rectifier potassium current which may play a significant role in the prolongation of repolarization by the drug in ventricular tissue.

Magnesium and the heart: antiarrhythmic therapy with magnesium.

Magnesium is an essential transmembrane and intracellular modulator of the electrical activity of cardiac cells. This review provides an up-to-date consideration of the cellular and clinical electrophysiological role of magnesium. This ubiquitous element seems to be important from both the theoretical and clinical point of view, because magnesium salts (MgSO4, MgCl2) administered intravenously are particularly effective in those arrhythmias in which the mechanism involves early or delayed after depolarization-induced triggered activity. The authors share the view that I.V. magnesium is the drug of choice in "torsade de pointes" ventricular tachycardia accompanying acquired long QT/QTU syndrome. It is complementary therapeutic agent in digitalis-induced tachycardias. Further studies are needed to elucidate magnesium's mode of action and efficacy in other types of clinical tachyarrhythmias.

Arrhythmias in organophosphate poisonings.

168 cases of organophosphate poisonings are reviewed with special respect to frequent arrhythmias. In 134 cases toxic repolarisation with QT prolongation, ST- and T- anomalies were present. 56 patients had arrhythmias and the prevalence of ventricular arrhythmias was impressive. In five patients a transient picture of myocardial infarction was seen. The great incidence of ECG alterations and arrhythmias necessitate the permanent monitoring of patients with organophosphate poisoning in an intensive care unit.

Hexamethylenebisacetamide modulation of thyroglobulin and protein levels in thyroid cells is not mediated by phosphatidylinositol-3-kinase: a study with wortmannin.

Hexamethylenebisacetamide (HMBA) induces in murine erythroleukemia cells (MELC) the commitment to terminal differentiation leading to globin gene expression. In the thyroid, HMBA acts as a growth factor and also as a differentiating agent. In the present paper, we studied the effect of HMBA on the very specific thyroid marker thyroglobulin (Tg) in two different thyroid cell systems, i.e., porcine cells in primary culture and ovine cells in long term culture. Using wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, we investigated whether this enzyme is involved in HMBA mode of action. We found that HMBA is a positive modulator of Tg production in porcine cells, but a negative effector in the OVNIS cell line. As all HMBA effects studied in the present paper, i.e., Tg production and total protein levels, are not inhibited by wortmannin, we suggest the non-involvement of phosphatidylinositol-3-kinase in HMBA mode of action.

[Familial periodic paralysis (hypopotassaemic form) (author's transl)]. / Familiäre paroxysmale Lähmung (hypokaliämische Form).

The case history of a mother and daughter with familial periodic paralysis serves to illustrate the features of the hypokalaemic form of this condition. The development of attacks in the child does not appear to be based on intermittent hyperaldosteronism as trigger mechanism. A good therapeutic response to the potassium-retaining preparation, triamterene is reported.

Formulation and in vitro examination of furosemide containing suppositories and preliminary experiences of their clinical use.

Rectal suppositories containing furosemide (4-chloro-N-furfuryl-5-sulfamoylanthranilic acid) and furosemide sodium were formulated with various suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be the best from the vehicle having various physical-chemical properties. The diuretic effect of the two suppositories was compared in a prospective, crossover clinical trial including 8 patients. Both preparations have induced an increase of urine flow, which was comparable to the diuretic effect of the tablet.

[Suicide with an unusual shotgun]. / Selbsttötung mit einem ungewöhnlichen Schussapparat.

The authors describe a special case of suicide, committed by a self-constructed nailgun. The inshot-wound, localized in the mouth, primarily remained undiagnosed. The patient survived two weeks and died of pulmonary embolism.

[Anti-arrhythmia therapy with Ca++-antagonists]. / Antiaritmiás kezelés Ca++-antagonistákkal.

A minireview is given of the theoretical and clinical knowledge relating to antiarrhythmic therapy with Ca++-antagonists. Following a brief recall of the basic cardiac electrophysiological elements, some primarily Ca++- and 'slow response'-dependent electropathological phenomena (ischaemia-induced local conduction delay, ST-T-alternans, early and delayed after depolarizations) are presented, to which roles are attributed in the development of re-entry, triggered automaticity and human cardiac arrhythmias. Next, those types of heart rhythm disturbances are discussed which can be treated in the hope of success with Ca++ entry blocking (class IV) antiarrhythmic agents.

[Scientometric and publication malpractices. The appearance of globalization in biomedical publishing]. / Scientometriás és publikációs praktikák. A globalizáció megjelenése az orvosi publicisztikában.

Attention is drawn to publication and scientometric malpractices utilized by biomedical authors who do not adhere to the accepted ethical norms. The difference between duplicate/redundant and bilingual publications is defined. In the course of discussion of the manipulations that may be observed in the field of scientometry, it is pointed out that abstract of congress lectures/posters can not be taken into consideration for scientometric purposes even if such abstracts are published in journals with impact factors. A further behavioral form is likewise regarded as unacceptable from the aspect of publication ethics: when a physician who has participated in a multicentre, randomized clinical trial receives recognition (in an appendix or in an acknowledgement of an article) as having contributed data, but assesses this appreciation as co-authorship and thereby attempts to augment the value of his or her publication activity. The effects of globalization on biomedical publication activity are considered, and evidence is provided that the rapidly spreading electronic publication for a give rise to new types of ethical dilemmas. It is recommended that, in the current age of Anglo-American globalization, greater emphasis should be placed on the development of medical publication in the mother tongue (Hungarian).

[Scientometrics and publishing in Hungarian medical science. Ethical and technical issues]. / A scientometria és a hazai szakirodalmi tevékenység. Etikai és technikai kérdések.

The authors present an account of the main ethical and technical aspects relating to the measurement of medical publication activities and the compilation of publications lists. It is demonstrated that the Anglo-American scientometric system (Institute for Scientific Information, USA) is currently gaining stable ground in Hungary. At the same time, however, there continues to be a place for a national publication index used to assess Hungarian-language publication activity, for the two systems conveniently supplement one another. The criterion system of medical publishing established by the International Committee of Medical Journal Editors (ICMJE) is described in detail, and is recommended for wide-ranging application in Hungary.

[The principles of pharmacotherapy for arrhythmia at the turn of the millenium]. / Az antiarrhythmiás farmakoterápia alapelvei az ezredfordulón.

A review is presented at the main causes of the change in paradigm that has occurred in the past 10 years in antiarrhythmic pharmacotherapy. The new attitude is ascribed to (1) the advances made in the application of non-pharmacological therapeutic modalities (radiofrequency catheter ablation, implantable antiarrhythmic devices), (2) the modification of therapeutic practice in response to the results of large-scale prospective randomized clinical trials, and (3) the proper recognition and appropriate appreciation of the frequently life-threatening proarrhythmic action of antiarrhythmic drugs. The current state of knowledge is discussed as concerns the anti- and proarrhythmic effects of the drugs available at present, and also their safe clinical use.

[Quinidine-induced syncope simulating transient cerebral ischemic attack]. / Tranziens cerebralis ischaemiás attak képében jelentkezó kinidin-syncope.

A case of quinidine-induced syncope with prevailing neurological symptoms is reported in which the transient right-sided hemiparesis and fluctuating soporific state was induced by recurrent torsades de pointes ventricular tachycardias. In connection with this case, attention is paid to the difficulties of differential diagnosis and to the consideration of cardiac and metabolic disorders mimicking TIA or ischaemic stroke.

[Cardiac electrophysiological effect and clinical use of adenosine]. / Az adenozin szív-elektrofiziológiai hatásai és klinikai alkalmazása.

A review is provided of the present state of knowledge relating to the cardiac electrophysiological effects of adenosine at ion channel and clinical levels. It is emphasized that intravenous adenosine is highly effective in terminating sinus node, atrioventricular (AV) nodal and AV-reciprocating reentrant tachycardias. In the course of an account of the antiarrhythmic indications of adenosine therapy, the main aspects of the diagnostic use of the nucleoside are briefly discussed. It is pointed out that adenosine treatment may possibly be accompanied by the occurrence of atrial and ventricular proarrhythmias, for at pharmacological dose of 6-12 mg this endogenous cardioprotective and antiarrhythmic agent is not devoid of side-effects.

[Electrocardiographic Osborn wave in hypothermia]. / Elektrokardiográfiás Osborn-hullám hypothermiában.

The authors report the first Hungarian case of electrocardiographic Osborn wave with accidental hypothermia (core temperature 32 degrees C). The cellular and ionic mechanisms of the development of J-wave-elevation and the cardiac electrophysiological and ECG changes caused by hypothermia are briefly reviewed. An account is presented of those conditions in which, in a few or in all ECG leads, an Osborn wave or distinct J-point-elevation may be observed.