[Sildenafil and nitric oxide inhalation in neonatal pulmonary hypertension. Three case reports]. / Sildenafil ed ossido nitrico inalato nel trattamento dell'ipertensione polmonare neonatale. A proposito di tre casi.

INTRODUCTION: Neonatal persistent pulmonary hypertension (NPPH) is characterised by persistently high pulmonary vascular resistance (PVR). Sildenafil has recently been suggested as an alternative to or an associative therapy with inhaled nitric oxide (iNO) to reduce mortality (10-40%) and morbidity (major neurologic disabilities among surviving newborns remains approximately 15-60%). The objective is to report three cases of NPPH treated with sildenafil in association of iNO. CASE REPORTS: Echocardiography examination of three newborn babies with respiratory distress syndrome and a gestational age between 33 and 39 weeks revealed pulmonary hypertension following early onset sepsis. Synchronized intermittent mandatory ventilation (SIMV) and surfactant therapy had no effect on oxygen saturation (SatO2) and oxygen alveolar-arterial difference (AaDO2). High frequency oscillatory ventilation (HFOV) and iNO therapy proved to be equally ineffective. Oral sildenafil was administered at 2 mg/Kg/6 hs. A gradual but significant improvement in oxygenation was achieved and a reduction in AaDO2 along with oxygenation index (OI) and pulmonary arterial pressure (PAP) was observed in the first 6-10 hrs after administration of sildenafil. The therapy was maintained for 36-48 hrs with total success. CONCLUSIONS: A beneficial pulmonary vasodilator effect was obtained in treating NPPH with sildenafil where conventional methods had failed. Sildenafil used in association with iNO reduces the duration of treatment, the quantity of iNO normally required and the associated toxic effects. A multicentric, randomized trial could be useful in demonstrating the safety, efficacy, doses and forms of administration of sildenafil.

Dyserythropoiesis in iron deficiency and in beta-thalassemia.

Nuclear and cytoplasmic abnormalities were quantitated in bone marrow erythroblasts from 15 patients with iron deficient anemia, 5 beta-thalassemia homozygotes, 5 beta-thalassemia heterozygotes, 6 S/beta-thalassemia double heterozygotes and 9 controls. The frequency of dyserythropoietic changes in iron deficiency was 11.90 +/- 5.02% (mean +/- SD) which is significantly higher than 3.36 +/- 1.16% obtained for the control group. The degree of dyserythropoiesis was negatively correlated with hemoglobin level (rS = 0.757). The frequency of dyserythropoietic changes obtained for the beta-thalassemia heterozygotes (5.23 +/- 1.45%) and for S/beta-thalassemia (7.13 +/- 2.00%) was elevated compared with the controls (P less than 0.05 and P less than 0.01, respectively). The highest frequency of dyserythropoiesis (19.88 +/- 7.40%) occurred among beta-thalassemia homozygotes. In all cases studied the abnormalities were observed mainly in the late erythroblasts. In addition, a peculiar cytoplasmic inclusion was observed in Leishman-stained bone marrow or peripheral blood erythroblasts from beta-thalassemia homozygotes, which is probably the result of precipitation of excess alpha-chain. This abnormality of thalassemia erythroblasts in Leishman-stained smears had not been previously reported.

Beta-thalassemia in Brazil.

1. Clinical, hematological, genetic and peripheral blood globin synthesis studies were carried out on 17 symptomatic Brazilian thalassemics and their parents who live in the northeast of São Paulo State. The group included 8 beta zero-thalassemia homozygotes, 7 carriers of at least one beta + gene, one delta beta zero/beta zero-thalassemia double heterozygote and one beta zero homozygote also carrying the alpha-chain variant Hb Hasharon (alpha 2(47) His beta 2). 2. The mean non-alpha/alpha ratio for globin biosynthesis of the patients lacking HbA (beta zero homozygotes and delta beta zero/beta zero double heterozygotes) was 0.26 +/- 0.11 (mean +/- SD), which is not statistically different from the value of 0.32 +/- 0.06 obtained for the carriers of at least one beta + gene. In contrast, the mean non-alpha/alpha ratio for the thalassemia major patients (0.22 +/- 0.07) was significantly lower than that obtained for the milder cases (0.34 +/- 0.06) although the beta/alpha ratios for the parents of the two groups were similar. 3. The heterogeneity within this group of Brazilian patients having two thalassemic genes, i.e. 60% who are beta zero homozygotes and 40% who are carriers of at least one beta + gene, is consistent with the Italian origin of most of these patients.

T-cell subsets in patients with aplastic anemia.

Abnormalities of lymphocyte subpopulations have been described in patients with aplastic anemia. In the present report we extend these studies by measuring T cell subsets identified by the presence of Fc receptors for IgM (T mu-lymphocyte) and IgG (T gamma-lymphocyte) in 22 patients and in 48 normal controls. The absolute number of T mu and T gamma lymphocytes was normal in the majority of cases. The percentages of T mu cells was increased in 4 cases and decreased in 2; T gamma cells were increased in 6 patients. The levels of serum immunoglobulins did not correlate with the T mu/T gamma ratio. The pathogenesis of aplastic anemia is discussed in terms of these immunological abnormalities.

Antibody-dependent cellular cytotoxicity in some lymphoreticular diseases.

Antibody-dependent cellular cytotoxicity mediated by K cells against chicken erythrocytes was measured in 113 patients with malignant lymphoreticular disorders and compared with 230 controls. The results were expressed as the specific cytotoxicity of a fixed number of cells and also by cytotoxic capacity, which measures the number of cytolytic units in 1 ml of blood. The values for cytotoxic capacity were normal in the group of untreated patients with non-Hodgkin's lymphomas, multiple myeloma or chronic lymphocytic leukemia and in most of the patients with Hodgkin's disease or acute lymphoblastic leukemia. However, decreased specific cytotoxicity was observed in these same lymphoid leukemia patients, which may be due to dilution of effector cells. The effect of chemotherapy in reducing K-cell activity is more evident in patients with multiple myeloma, followed by patients with Hodgkin's disease, and finally by patients with non-Hodgkin's lymphomas. No case of K-cell neoplastic disease was observed in this series.

[Importance of ultrasonographic monitoring in renal malformations]. / L'importanza del monitoraggio ecografico nelle malformazioni renali.

Routine ultrasound imaging in pregnancy reveals more abnormalities in the fetal urinary tract than any other system. The mild dilatation of the pelvi-caliceal system can be easily demonstrated approximately 80% of neonates with a prenatal diagnosis of uropathy shows neither symptom at birth. The follow-up study of four cases of mild fetal kidney abnormalities was taken to assess the postnatal morbidity of these children and to document the natural history of the ultrasound imaging.

[Peritonitis caused by meconial ileus in a very premature patient. Presentation of a clinical case]. / Peritonite da ileo meconiale in paziente con prematurità grave. Presentazione di un caso clinico.

The Authors describe a case of meconium peritonitis in a low birth weight infant with associated malrotation of the intestines. We retrospectively analyzed the surgical approach during the stages of the disease. The purpose of this study is to stress a conservative surgical therapy (peritoneal cavity toilette and ileostomy), followed thereafter by intensive care, which should carefully balance metabolic and nutritional needs; it's then possible to perform a second look (canalization) only three mounths later, when a reasonable growth is achieved. A multidisciplinary approach favoured the positive outcome.

[The surgical treatment of fixed aortic subvalvular stenosis]. / Trattamento chirurgico delle stenosi sottovalvolari aortiche fisse.

Over the past 5 years, 45 patients (11 adults and 33 children) have undergone operations for discrete and fixed subaortic stenosis. The resection of the subvalvular membrane or the fibromuscular collar was the procedure of choice. 28 patients underwent myectomy and/or myotomy. None patients died during operations. No significant symptoms and gradients remained after operation. We conclude that in the surgical management of fixed discrete subaortic stenosis myectomy and myotomy in addition to membranectomy produces better relief of the left ventricular outflow obstruction than do membranectomy alone.

A comparative study of lymphocytes in effusions of patients with tuberculosis or malignant disease.

The diagnostic value of the determination of the relative distribution of B (SmIg-positive) and T (E rosetting) cells in the blood and in pleural or ascitic effusions was evaluated in 10 patients with tuberculosis and in six with malignant diseases. A higher percentage of T and a lower percentage of B lymphocytes in serous fluids than in peripheral blood was observed for both groups of patients. We conclude that this procedure is valueless in differentiating between tuberculosis and malignant diseases when effusions containing predominantly lymphocytes and devoid of metastatic cells are examined.

Splenic function in sickle-cell diseases.

Studies of splenic function were carried out on patients with sickle-cell diseases by the measurement of the clearance of autologous heat-damaged 99mTc-labelled erythrocytes from circulation and into the spleen, the spleen area by a scintillation scanning, the enumeration of pitted erythrocytes by direct-interference microscopy, and the percentage of irreversibly sickled cells (ISC) and of cells with Howell-Jolly bodies. All measurements were performed in seven HbS homozygotes, 10 patients with sickle cell beta(0)-thalassaemia (S/beta(0)-thalassaemia), three patients with sickle-cell disease (SC), four AS heterozygotes and 17 controls. Three different patterns of splenic function were observed among the 20 patients with symptomatic sickle-cell diseases: six patients had enlarged hyperactive spleens, four had enlarged hypoactive spleens, and in 10 patients no splenic activity was detected. The percentage of ISC was higher in sickle-cell anaemia than in S/beta (0)-thalassaemia and very low in SC patients. These results would suggest that the spleen goes through similar successive functional stages in the sickle-cell diseases, namely enlargement in the early years of life, which is followed by hypoactivity and finally atrophy. This evolution seems to be faster in sickle-cell anaemia than in S/beta(0)-thalassaemia and SC disease.

Bone marrow and peripheral blood globin chain biosynthesis in iron deficiency.

Globin chain synthesis was studied in 13 iron-deficient patients. The mean whole-cell globin alpha/beta ratio in the peripheral blood of 11 patients was 1.05 +/- 0.06 which is similar to the value 0.99 +/- 0.08 obtained for 10 controls. The ratios obtained for stroma-free globin were not significantly different from those of whole cell preparations. In contrast, the alpha/beta ratio of bone marrow was 0.73 +/- 0.14 in 10 iron deficient patients, which is significantly lower than that of controls. Two other patients had decreased alpha/beta ratios in the peripheral blood, probably because of the presence of an alpha-thalassemia gene. These results demonstrate a reduced rate of synthesis of alpha chains relative to that of beta chains in the bone marrow of iron-deficient patients that is not demonstrable in the peripheral blood.

Unbalanced globin synthesis in bone marrow of beta-thalassemia heterozygotes.

Globin-chain synthesis was studied in the peripheral blood and bone marrow of eight beta-thalassemia heterozygotes. Whole cell globin was prepared immediately after the labeling experiment. Chain separation of the bone marrow globin of each case was carried out with both the original material and after filtration on Sephadex G 100. The beta/alpha ratios obtained were (mean +/- SD): 0.46 +/- 0.05 in the peripheral blood, 0.61 +/- 0.06 in the unfiltered bone marrow globin, and 0.52 +/- 0.05 in the bone marrow globin after gel filtration. The results show that beta-thalassemia heterozygotes have a similar beta-chain deficiency in reticulocytes and bone marrow cells, provided whole cell globin is used, which avoids the removal of free alpha-chains.

Cytogenetic remission in a Ph1-positive case of chronic myelogenous leukaemia.

Unusual cytogenetic findings in a case of chronic myelogenous leukaemia in the course of an aplastic crisis induced by busulfan therapy are reported. The proportion of Ph1-positive cells in bone marrow aspirates fell from 100% before treatment to 8.6% following aplasia. It increased gradually during recovery, and normal cells still represented 25.7% of the metaphases 20 months later. After a 38-months' remission without therapy the disease relapsed and the Ph1 chromosome was found in 100% of the bone marrow cells.

T-lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia.

A decrease in the absolute number of total lymphocytes, OKT3+ and OKT4+ lymphocytes, and a normal number of OKT8+ lymphocytes were found in the peripheral blood of patients with aplastic anemia. The OKT4:OKT8 ratio was decreased in patients due to a reduction in the percentage of OKT4+ cells and 3 out of 18 patients had a ratio less than 1. The values of the OKT4:OKT8 ratio were not associated either with the severity of the disease or with treatment with androgens. There was no correlation between the OKT4:OKT8 ratio and the number of transfusions received by patients. On the other hand, studies performed with bone marrow lymphocytes showed that the OKT4:OKT8 ratio for both patients and controls was lower than that of the peripheral blood. Since the ratio of OKT4:OKT8 cells in aplastic and control bone marrow was similar no direct pathogenic role can be assigned to the marrow for the imbalance detected in the peripheral blood.

Some immunological studies in aplastic anaemia.

Peripheral blood studies in 29 patients with aplastic anaemia showed decrease in the mean numbers of total lymphocytes, T and B lymphocytes and monocytes. Quantitation of serum immunoglobulins carried out in 22 patients showed normal results in most cases. Although the significance of these immunological changes in the development of aplastic anaemia is not established they may represent a factor in addition to neutropenia in the pathogenesis of infections in this disease.

beta+-Thalassemia intermedia with low HbF.

Two cases of homozygous beta+-thalassemia intermedia have been detected in a Brazilian family of Portuguese and German extraction. The patients are 39 and 43 years old, showed a normal somatic and sexual development and had been transfused only occasionally. Red blood cell morphology was similar to that of thalassemia major, but they had unusually low levels of HbF (5.0% and 6.8%). Globin chain synthesis measured in reticulocytes was in the same range as other beta-thalassemia homozygotes. One or both genes in this family must be a particularly mild beta-thalassemia allele, despite the fact that the heterozygote members of the family presented clinical, hematological, and biochemical features indistinguishable from the typical heterozygotes for the beta-thalassemia trait with high HbA2.

Thalassaemia intermedia in a family with beta 0-thalassaemia and Hb Hasharon.

A Brazilian family of Italian descent is described in which the beta-thalassaemia gene is interacting with an alpha chain variant Hb Hasharon (alpha 47 Asp leads to His). One patient who was affected by homozygous beta 0-thalassaemia and heterozygous alpha Hasharon displayed the clinical picture of thalassaemia intermedia. Her haemolysate contained 8.6% Hb F Hasharon (alpha 2 Hasharon gamma 2) and 1.1% Hb A2, the remaining haemoglobin being Hb F. Hb A was not detected. Globin chain synthesis in reticulocytes showed non-alpha/total alpha ratios of 0.29, 0.39, and 0.73 respectively for the patient, the mother, and the father, who is heterozygous for both the beta 0-thalassemia and Hb Hasharon genes. The possible contribution of Hb Hasharon heterozygosity to the less severe expression of homozygous beta 0-thalassaemia is discussed.