Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.

Patients with hypomorphic mutations in the RAG1 or RAG2 gene present with either Omenn syndrome or atypical combined immunodeficiency with a wide phenotypic range. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but data are scarce. We report on a worldwide cohort of 60 patients with hypomorphic RAG variants who underwent HSCT, 78% of whom experienced infections (29% active at HSCT), 72% had autoimmunity, and 18% had granulomas pretransplant. These complications are frequently associated with organ damage. Eight individuals (13%) were diagnosed by newborn screening or family history. HSCT was performed at a median of 3.4 years (range 0.3-42.9 years) from matched unrelated donors, matched sibling or matched family donors, or mismatched donors in 48%, 22%, and 30% of the patients, respectively. Grafts were T-cell depleted in 15 cases (25%). Overall survival at 1 and 4 years was 77.5% and 67.5% (median follow-up of 39 months). Infection was the main cause of death. In univariable analysis, active infection, organ damage pre-HSCT, T-cell depletion of the graft, and transplant from a mismatched family donor were predictive of worse outcome, whereas organ damage and T-cell depletion remained significant in multivariable analysis (hazard ratio [HR] = 6.01, HR = 8.46, respectively). All patients diagnosed by newborn screening or family history survived. Cumulative incidences of acute and chronic graft-versus-host disease were 35% and 22%, respectively. Cumulative incidences of new-onset autoimmunity was 15%. Immune reconstitution, particularly recovery of naïve CD4+ T cells, was faster and more robust in patients transplanted before 3.5 years of age, and without organ damage. These findings support the indication for early transplantation.

Liver transplantation for severe hepatic graft-versus-host disease in two children after hematopoietic stem cell transplantation.

Chronic graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT). After the skin, the liver is the second, most frequent target of GVHD, which presenting with hyperbilirubinemia, elevated liver enzymes, and coagulopathy. Progressive destruction of small intrahepatic bile ducts causes vanishing bile duct syndrome and leads to end-stage liver disease. We report 2 successful cases of orthotopic liver transplantation performed in children with severe GVHD after hematopoietic stem cell transplantation from a matched unrelated donor (HSCT-MUD).

[Mediators of the inflammatory response in the course of acute pancreatitis]. / Mediatory procesu zapalnego w przebiegu ostrego zapalenia trzustki.

Acute pancreatitis (AP) is one of the most frequent causes of acute inflammatory states in the abdominal cave. In majority of cases the disease, if properly treated, has a selflimiting course and terminates in several days. However, in about 20% of patients with diagnosed AP haemorrhagic and necrotic lesions of the pancreas occur what effects in multiple organ injury and high mortality of these patients. Early diagnosis of haemorrhagic and necrotizing outcome of the disease is difficult, therefore new markers of necrotizing acute pancreatitis are still under research. Cytokines mediating inflammatory process may provide some specific information on the expected outcome of acute pancreatitis. Article reviews the information about the role of inflammatory cytokines in development and outcome of acute pancreatitis.

[Arrhythmia in patients with hypertrophic cardiomyopathy during an exercise test with 24-hour Holter monitoring]. / Zaburzenia rytmu u chorych z kardiomiopatia przyrostowa w próbie wysilkowej i 24-godzinnym monitorowaniu ekg metoda Holtera.

Thirty patients with hypertrophic cardiomyopathy (HCM), (20 men and 10 women, age 16-55, mean 37 +/- 8 years) underwent exercise test done on bicycle twice to estimate effort tolerance before drugs. In all patients a 24-hour ekg Holter monitoring was also performed. During exercise test heart rhythm disturbances were noticed in 2 patients (7%). One had a 2-second sinus arrest, in the other ventricular bigeminity was observed. Twenty two patients (79%) had rhythm or conduction disturbances in Holter monitoring. In 2 (7%) rhythm generation and conduction abnormalities, in 7 (23%)-supraventricular and in 13 (43%)-ventricular arrhythmia. Ten of them (33%) had Lown class IVa and IVb arrhythmia. In conclusion we suggest that exercise test done on bicycle ergometer is a safe method to estimate effort tolerance in patients with HCM and usually does not induce rhythm disturbances. Holter monitoring is more effective than exercise test in revealing cardiac arrhythmia.

[Effects of long term oxygen therapy in patients with idiopathic pulmonary fibrosis. II. Effect of oxygen therapy on function of heart ventricles]. / Efekty przewleklej domowej tlenoterapii u chorych z idiopatycznym zwlókniajacym zapaleniem pluc. Czesc II: Wplyw tlenoterapii na funkcje komór serca.

The aim of this study was to assess the effect of chronic home oxygen therapy on cardiac function in patients with idiopathic interstitial lung fibrosis. Ten patients (Group A) received standard pharmacological treatment (prednisone 10-15 mg/day) and supplementary home oxygen therapy (mean 16.4 h/day) for the period of 4 years. Eight patients (Group B) received pharmacological treatment alone for the same period of time. Left ventricular ejection fraction was measured with a scintillation probe. Right and left ventricular function was also assessed by means of echocardiography. All measurements were taken at the beginning of study and repeated at the end of the 4 year follow-up. Anatomical and functional deterioration was slower in group A than in group B. Statistically significant differences between the groups at follow-up were found with respect to the right ventricle-early inflow velocity and tricuspid E/A ratio. Changes in left ventricular function were also different between the groups. A significant decrease in ejection fraction and mitral E/A ratio was observed in group B, while the corresponding changes in group A were not significant. These results suggest that chronic home oxygen therapy attenuates cardiac dysfunction in patients with idiopathic interstitial lung fibrosis.

[Congenital methemoglobinemia found in an adult. Case report]. / Methemoglobinemia wrodzona wykryta u doroslej chorej. Opis przypadku.

Cyanosis in a 36 year old patient which persisted 20 years after a successful surgical closure of her patent foramen ovale has been finally diagnosed as due to congenital methemoglobinemia: a 28% level of methaemoglobin and no activity od NAD-dependent methaemoglobin reductase were found. Erythrocyte antioxidative system was studied i.e. glutathione peroxidase, reductase, transferase, superoxidase dismutase and glucose-6-phosphate dehydrogenase. Increased activity was disclosed of superoxide dismutase and glucose-6-phosphate dehydrogenase in erythrocytes in comparison to normal individuals as well as increased concentration of lipid peroxidation products coexisting with methaemoglobin reductase deficiency.

[Treatment of recent myocardial infarction during menstruation--presentation of a case]. / Leczenie fibrynolityczne swiezego zawalu serca w czasie menstruacji--opis przypadku.

A young woman was admitted because of recent myocardial infarction (MI). Although she displayed menstruation bleeding, thrombolytic therapy with tpA was instituted. This resulted in full reperfusion and uneventful clinical course of MI. There was no prolongation of menstruation. Fibrinolytic treatment in women with MI and menstruation seems to be a safe procedure.

[Pro-arrhythmic effects of antiarrhythmic drugs in patients with ischemic heart disease]. / Proarytmiczne dzialanie leków Przeciwarytmicznych u chorych z choroba niedokrwienna serca.

The incidence of proarrhythmic effect of antiarrhythmic drugs (AADs) in not well documented. The aim of the study was to assess the frequency od proarrhythmia in patients with ischemic heart disease (IHD) and ventricular premature beats (VPBs) in whom various class I, II and III AADs were tested by 24-h Holter ecg. All data were collected in a prospective manner. Our material consisted of 639 patients with IHD and VPBs (Lown's grade 2-5). The mean age was 53 years. 63% of patients had previously myocardial infarction. 15% and 3% had documented ventricular tachycardia (VT) or ventricular fibrillation (VF), (VF), respectively. Baseline Holter monitoring revealed repetitive VPBs or R on T phenomenon in 64% of cases. Plasma electrolytes level, renal and hepatic function were normal. Antiarrhythmic therapy was guided by repeated 24-h Holter ecg on a maintenance dosage of the drug. Propranolol was a drug of first choice. Disopyramide or mexiletine was added if propranolol alone was found to be ineffective in control Holter ecg. Amiodarone was a drug of a next choice. It was allowed modify the treatment in patients with contraindication to propranolol, clinical VT/VF or high grade VPBs. 794 drug tests were conducted. Number of tests/patient ranged 1-4. The following AADs were assessed: propranolol (352 tests), disopyramide (280 tests), mexiletine (73 tests), amiodarone (89 tests). Aggravation of arrhythmia was defined by modified criteria proposed by Velebit: 1) greater than or equal to 4-fold increase in VPBs, 2) greater than or equal to 10-fold increase in couplets or salvoes, 3) occurrence of VT. Proarrhythmia was recognized when at least one criterion was present.(ABSTRACT TRUNCATED AT 250 WORDS)

[Possibilities of echocardiographic evaluation of hemodynamic disorders in hypertrophic cardiomyopathy]. / Mozliwosci echokardiograficznej oceny zaburzen hemodynamicznych w kardiomiopatii przerostowej.

In a group of 59 patients with hypertrophic cardiomyopathy relationship between echocardiographic parameters (interventricular septal thickness, left ventrical diastolic diameter, presence of SAM, distribution of hypertrophy) and certain hemodynamic measurements (diastolic compliance, left ventricular end-diastolic pressure, intraventricular pressure gradient, mean wall thickness and left ventricular mass index) were assessed. Substantial elevation of left ventricular end-diastolic pressure (LVEDP greater than 20 mmHg) was significantly more prevalent among patients with small left ventricular diameter and gross septal hypertrophy. Extensive ventricular hypertrophy (Maron type III) was not characterized by any distinctive hemodynamic pattern. Presence of SAM reaching interventricular septum was indicative of left ventricular outflow obstruction.

[Relation between echocardiographic image and the electrocardiogram in hypertrophic cardiomyopathy]. / Zaleznosc miedzy obrazem echokardiograficznym a elektrokardiogramem w kardiomiopatii przerostowej.

Authors analyzed the correlation between anatomic changes estimated by echocardiographic examination and electrocardiographic recordings in group of 104 patients with hypertrophic cardiomyopathy. It was stated that morphological type III by Maron (8) is characterized, in comparison with other types, by significantly lower percentage of right ventricular hypertrophy and higher percentage of QTc interval prolongation, whereas percentage of patients with mitral or left ventricular hypertrophy was insignificantly higher. P Mitrale was significantly more often observed in patients with left ventricular diastolic dimension less than 35 mm. Generally ecg recordings had no distinct markers of the extent and localization of hypertrophic changes. Authors conclude that the unmistakable recognition of the anatomical type of hypertrophy basing on electrocardiogram is possible.