[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.

[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.

[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.

[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.

Hemichrone formation during hemoglobin zuricha denaturation

Os espectros de absorçäo obtidos por ressonância eletrônica paramagnética (REP) após oxidaçäo, armazenamento e aqueciemnto de Hb Zurich revelaram numerosos sinais na regiäo de alto campo (g=-) que säo indicativos da formaçäo de hemicromos. Espectros de absorçäo ópticos na regiäo visível obtidos da Hb Zurich oxidada ou de seu precipitado formado espontaneamente mostram aspectos característico da formaçäo de hemicromos. Os sinais de REP aumentam em g =-2) proporcionalmente ao decréscimo em g =-6,37. Além do mais, a relaçäo entre os valores de absorbância em 540 nm (heme) e 280 nm (proteína) näo se alteram durante o aquecimento da Hb Zurich a 50-C e säo similares no precipitado espontâneo desta hemoglobina en na HbA. Estes achados indicam que näo há perda do heme durante os estágios iniciais da desnaturaçäo da Hb Zurich

Hemichrome formation during hemoglobin Zurich denaturation.

Electron paramagnetic resonance (EPR) spectrum of hemoglobin Zurich, after oxidation, storage and heating, showed several absorption derivatives in the high field region (g approximately equal to 2) which are indicative of hemichrome formation. Characteristic visible spectra of hemichromes were observed for oxidized Hb Zurich and for its spontaneous precipitate. The proportional increase of EPR signals at g approximately equal to 2 and decrease at g = 6.37, the constant ratio of absorbance at 540 nm to 280 nm during heating, and the similarity of this ratio for spontaneously precipitated HbA and for Hb Zurich indicate that heme is not lost during the first steps of Hb Zurich denaturation.

Splenic function in haemophilia.

Studies of splenic function were carried out on 17 haemophilic patients over 9 years of age, and 20 control patients. The clearance of autologous heat-damaged 99mTc-labelled erythrocytes from circulation and into the spleen was measured: the spleen area by scintillation scanning, and the enumeration of pitted erythrocytes by direct interference microscopy. Splenic enlargement was observed in 10 patients (59%). On the basis of the clearance half-time, splenic function was normal in 3/13 (23%) and hyperactive in 9/13 (69%) patients. One heavily transfused patient had a hypoactive spleen with long clearance half-time, slow splenic uptake of radioactivity and high pit counts. These results demonstrate that the spleen of haemophiliacs is usually enlarged and functionally abnormal.

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.

The association of Hb Stanleyville II with alpha thalassemia and Hb S.

Two unrelated families are described which include two heterozygotes for Hb Stanleyville II, two compound heterozygotes for Hb Stanleyville II and Hb S, and one compound homozygote for the two abnormal hemoglobins. The homozygote did not produce normal alpha chains, the abnormal chains accounted for 32-35% of the total alpha chain of four heterozygotes, and the alpha/non-alpha synthetic ratios were in the range 0.59-0.77. These data demonstrate the presence of an alpha-thalassemia gene linked to the alpha-Stanleyville II mutation.

Discrepancy between pit counting and spleen function tests in nutritional anemias and hemoglobinopathy C.

An increased percentage of erythrocytes with crater-like indentations (pits) when viewed under interference contrast microscopy is accepted as indicative of splenic hypofunction. The percentage of pitted erythrocytes was above the upper limit of the normal range (0.0-3.2%) in 6 patients with megaloblastic anemia (4.6-22.6%), 8 patients with iron deficient anemia (5.6-21.0%) and 6 patients with HbC diseases (12.5-45.0%). However, the spleen function was normal or hyperactive when evaluated by the rate of removal from the circulation of heat-damaged 99mTc-labeled autologous erythrocytes. Thus, in these diseases, there is a discrepancy between pit counting in the peripheral blood and other spleen tests.

Red cell pits appear preferentially in old cells after splenectomy.

The percentage of erythrocytes with pits in the peripheral blood after splenectomy was followed in 4 patients. The pit counts started to increase soon after surgery and were above 20% on the 20th postsplenectomy day. The results demonstrate that the majority of pits developed in circulating erythrocytes. Two other patients with autoimmune hemolytic anemia who had failed to respond to splenectomy presented an increase of pit counts from 5.5-13% to 29.8-47.4%, accompanying an increase of erythrocyte life-span during corticosteroid treatment. The data indicate that pits are formed preferentially in older erythrocytes.

Aspects of splenic hypofunction in old age.

The weight of the human spleen decreases in old age. The percentage of erythrocytes with pits observed by interference contrast microscopy was significantly higher in 39 elderly subjects (median 4.2%, range 1.2%-14.6%) than in 34 younger controls (median 1.4%, range 0.6%-6.2%). Further evidence of splenic hypofunction was obtained from 7 elderly people with increased pit counts: the removal from circulation and accumulation into the spleen of heat-damaged autologous erythrocytes was abnormally slow. However, no difference in the spleen area of the same subjects measured by scintillation scanning was observed in comparison with normals. Thus, the weight reduction of spleen in old age is accompanied by a decrease in splenic function.

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.

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.

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.

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.

Treatment of sickle cell diseases with aspirin.

The effects of long-term aspirin for the treatment of sickle cell disease were compared with placebo in a double-blind trial completed by 29 patients. Each patient was submitted to a 5-month period of treatment with aspirin (median dose 31 mg/kg/day) and an equivalent period with placebo. No clinical or laboratory differences were observed between the two phases, including the frequency of painful crises and infectious episodes, hemoglobin concentration, PCV, reticulocytes, Hb F, bilirubin, irreversibly sickled cells, filterability of red cell, sickling in vitro and hypoxia-induced potassium loss.