Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia.

Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD(+) patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 µg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 µg/kg platelet responses, defined as platelet count ≥ 30 × 10(9)/L and an increase in platelet count by > 20 × 10(9)/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.

Expression of estrogen receptor beta wt isoform (ERbeta1) and ERbetaDelta5 splice variant mRNAs in sporadic breast cancer.

PURPOSE: In addition to Estrogen Receptor alpha (ERalpha) and Progesterone Receptor (PR), the Second Estrogen Receptor (ERbeta) appears to play an important role not only in estrogen signaling, but also in the pathogenesis of cancer in estrogen dependent tissues. The existence of various isoforms and splice variants of both ERs additionally complicates elucidation of their physiological role and involvement in the process of carcinogenesis. METHODS: In this study, the expression of ERbeta1 mRNA (wild type of beta receptor) and splice variant ERbetaDelta5 mRNA (which codes for truncated protein) was measured by the quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and correlated with ERalpha and PR protein levels and with clinical and histopathological parameters. RESULTS: We found the inverse correlation of ERbetaDelta5 mRNA expression with the levels of PR and ERalpha proteins in the group of postmenopausal patients; we also report the lower expression of ERbeta1 and ERbetaDelta5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller ones (< or =20 mm, T1). The decrease of ERbetaDelta5 mRNA expression in larger tumors is found to arise from ER-positive breast carcinomas. In addition, the portion of tumors with concomitant high expression of both transcripts matches up the known percentage of tumors resistant to endocrine therapy in patients with different ER/PR status. CONCLUSIONS: As far as we know, this is the first study in which ERbetaDelta5 mRNA splice variant was quantified by real-time RT-PCR in the clinical samples of breast cancer tissue. Until now, the focus of clinical reports was the level of ERbeta1, ERbeta2, and ERbeta5 isoforms. The higher expression of ERbetaDelta5 mRNA is associated with the indicators of low biological aggressiveness of tumor (low tumor size within ER-positive status in our study) suggesting that the uncontrolled local tumor growth may occur as the expression of ERbetaDelta5 mRNA decreases in estrogen-dependent breast cancer.

[Prognostic value of dobutamine stress echocardiography in patients with terminal renal insufficiency undergoing hemodialysis--a 5-year follow up].

INTRODUCTION: Patients with end-stage renal failure have high morbidity and mortality rates due to cardiovascular complications. Screening for coronary heart disease in these patients is of utmost importance. The aim of this study was to investigate the prognostic value of the dobutamine test in patients on hemodyalisis during a 5-year follow-up period. MATERIAL AND METHODS: During the pretransplantation period, 24 patients on chronic hemodialysis underwent echocardiography and dobutamine echocardiography. The average age of patients was 51.50 +/- 7.35 years. The mean duration of dialysis was 74 +/- 40 months. RESULTS: The dobutamine stress test was positive in 50% of patients, and undefined in 12.5%. The wall motion score index before the test was 1, and after the test it was 1.54 +/- 0.27. There were no serious complications. Left ventricular mass, diastolic and systolic dimension and posterior wall were significantly higher in patients with positive dobutamine stress results and they were associated with late cardiac morbidity and mortality. Five-year survival in patients with positive dobutamine stress results was 33.3% and 52.3% in patients with negative dobutamine results. Causes of mortality were as follows: cardiac 45.4%, cerebrovascular 18.1%, other causes 36.4%. Cardiogical complications were not the cause of death in any of the patients with negative dobutamine results. In dobutamine positive group 62.5% died from cardiological complications. During the 5-year period, cardiac death and manifest coronary disease occurred in 75% of patients with positive dobutamine stress results and only in one patient with negative dobutamine results. Sensitivity was 75%, specificity 89% and positive predictive value 90%. CONCLUSION: Dobutamine stress echocardiography has a good predictive value for future cardiac events in hemnodyalisis patients, and in screening for coronary disease.

[Leiomyomas and massive digestive hemorrhages--case reports of patients diagnosed in 2004].

INTRODUCTION: During 2004, there were 6 patients with leiomyomas diagnosed and treated at the Department of Gastroenterology and Clinical Pathology of the Zemun Clinical Center. The most common location of these benign submucosal tumors is stomach, followed by small intestine and large intestine. CASE REPORT: The most common symptoms of these patients were massive intestinal hemorrhage, with haematemesis and melaena. Hemorrhages resulted from superficial lesions, caused by pressure of the tumour on the intestinal blood vessels. A significant contribution in reaching the final diagnosis and selecting appropriate therapeutic approach was provided by CT and arteriography. Most patients underwent surgical treatment, which provided precise diagnosis (based on histopathologicalfindings), and at the same time a definite therapeutic procedure. DISCUSSION AND CONCLUSION: According to the literature data, gastrointestinal leiomyomas account for 20%-30% of all types of gastrointestinal tumors. Our research revealed that the incidence of leiomyomas was significantly lower within our group of patients, accounting for 12% of all benign gastrointestinal tumors. They were also the main cause of hemodynamic instability in our patients having massive and recurrent intestinal hemorrhages, which is not often seen in practice. All of them originated either from muscularis propria or muscularis mucosae. These tumors are often an accidental finding at autopsy, especially if they are smaller than 3 centimeters and not followed by consequential complications. Presently, endoscopic ultrasonography is considered to be the the most accurate procedure in the diagnosis of leiomyoma, with a diagnostic specificity that is superior to other imaging techniques.

[An unusual cause of complete atrioventricular block--a case report].

INTRODUCTION: Complete atrioventricular block is a serious disorder, since patients may be asymptomatic. However, it is an important risk for sudden cardiac death. CASE REPORT: A 48-year old male patient was admitted to the coronary care unit, due to recurring substernal chest pain. It was followed by fatigue, weakness and confusion, it lasted more than half an hour and occurred twice. Loss of consciousness did not occur. The patient had a tick bite two months earlier. Physical examination was unremarkable, except for low heart rate (50/minute) electrocardiogram showed a complete atrioventricular block with narrow QRS complexes and good ventricular function. Elevation of ST segment was observed in the inferior ECG leads, with reciprocal ST depression in precordial leads; it was highly suspicious for acute myocardial infarction, but markers of myocardial necrosis (Troponin, Creatine kinase-MB) were normal. The chest pain recurred without evolutive changes in the electrocardiogram or increase in markers of myocardial necrosis. Tests for Lyme disease were negative, too. The cause of atrioventricular conduction disturbance was found by transthoracic echocardiography. A giant tumor was found in the right atrium and right ventricle. Further examinations excluded its secondary cause and the patient was sent to surgery. The tumor was inoperable and bled excessively. Although permanent pacing was performed, the patient died suddenly after dismisal. CONCLUSION: We can conclude that a giant primary tumor of the heart can be asymptomatic for a long time causing complete atrioventricular block, and in this case it clinically presented as acute myocardial infarction. Echocardiographic examination was the main diagnostic tool in our case.

[Cervical lymphodenopathy--a single presentation of sarcoidosis?].

BACKGROUND: Sarcoidosis is a chronic inflammatory disease, commonly found in lungs and hilar lymph nodes, but multiple organs could be involved. The diagnosis is based on specific pathohistology which should be always combined with clinical, radiological and laboratory findings. CASE REPORT: A patient initially presented with pneumonia, and treated with antibiotics, but with the general symptoms that persisted despite radiological resolution of lung infiltration was reported. The further diagnostic procedures revealed the presence of sarcoid granulomas in cervical lymph nodes. The peripheral lymph nodes are often affected in the early course of the disease, but it is difficult to distinguish if the illness is a sarcoid reaction to lung infection or a acute onset of sarcoidosis. CONCLUSION: The detection of sarcoid granulomas in cervical lymph nodes should be precisely analyzed for the presence of sarcoidal changes in other tissues, primarily in the lungs tissue. Early diagnosis of lung sarcoidosis is significant, especially in the light of the fact that the latest studies point out that the prednisone therapy, started immediately after the diagnosis has been made, renders positive effects also in asympthomatic patients in II and III phase of the disease.

[Agranulocytosis induced by metamizole and its management with granulocyte growth factor]. / Agranulocitoza izazvana metamizolom i terapija granulocitnim faktorom rasta.

Drug-induced agranulocytosis was defined as a severe selective neutropenia caused by an unexpected drug reaction. Metamizole was the most common nonopioid analgesic drug associated with agranulocytosis. It was also associated with combined blood dyscrasias and other severe immunologic disorders. The risk of agranulocytosis by metamizole seemed to be considerably higher than estimated formerly. Modern management with broad-spectrum antibiotics and haematopoietic growth factors reduced the mortality in those patients. Two cases of agranulocytosis caused by metamizole were reported.