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Biomedical subjects

G Masera

Publications and source records attributed to G Masera.

At least 163 records · Page 9Linked to original sources

Correlation of gonadal function with histology of testicular biopsies at treatment discontinuation in childhood acute leukemia.

Testicular open-wedge biopsy was performed in 35 children in complete remission from acute lymphoblastic leukemia without clinical signs of leukemic testicular infiltration at the time of treatment discontinuation. Histological investigation showed thickening of the tunica propria of the seminiferous tubules in 13 of 35 patients. In 5 of 35 patients, the tubular fertility index was markedly reduced; in 5 of 6 pubertal patients, decreased spermatogenesis or aplasia of germinal epithelium was observed. Histologic damage was found mainly in the germinal cells both in patients treated with cytosine arabinoside and cyclophosphamide and in those treated with antiblastic drugs not considered damaging to the gonads. The extent of impairment was independent of age at start of treatment. On the other hand, endocrinological investigation carried out at the crucial moment of treatment suspension showed normal hypothalamic-hypophyseal-gonadal function as well as normal anthropometric data, bone age, and pubertal stage in the majority of patients. Testicular leukemia was found in only one patient (2.8%) whereas three children with negative testicular biopsies had testicular relapses within 7 months. Therefore, in view of the limits of light microscopy in diagnosing leukemic infiltration at treatment discontinuation, we propose the use of more sophisticated techniques, possibly within 6 months of suspension of therapy.

Adolescent↗

Hepatitis B or non-A, non-B virus infection in multitransfused thalassaemic patients.

We undertook a four year study of 128 thalassaemic patients who had undergone several transfusions, to determine the incidence of hepatitis B virus markers and the activities of transaminases in their sera each month. The results showed that the possibility of these patients contracting hepatitis B virus infection is still high, although on only one occasion was a transient antigenaemia found, indicating low viral replication. Furthermore, the probability of contact with hepatitis B virus increases with the number of transfusions and, therefore, with age. About 25% of these patients were positive for hepatitis B markers and 80% for other hepatitis markers including the case of cytomegalovirus hepatitis.

Adolescent↗

Chronic liver disease in children with leukemia in long-term remission.

Liver disease during chemotherapy and after its completion was studied in 103 leukemic children in long-term remission. Seventy developed chronic liver disease during therapy; 22 out of 56 with adequate follow-up showed persisting abnormality or deterioration of liver function after stopping therapy. In 38 studied prospectively, biopsies were obtained at treatment withdrawal. Five showed chronic lobular, 17 chronic persistent, 9 chronic active hepatitis whereas 7 had minimal changes. These children had transiently detectable serum hepatitis-B virus (HBV) markers during (44.4%), at completion of (7.8%) and subsequent to (48.3%) chemotherapy. Serum HBV markers correlated significantly with both severity of histologic changes (P less than 0.05) and persistent biochemical abnormalities for over 6 months after treatment suspension (P less than 0.001). No direct relationship was found between drug administration and liver damage. The data from the study suggest that in leukemic children viral infections contribute to chronic liver damage, which can jeopardize the long-term prognosis of acute leukemia.

Acute Disease↗

Evidence of non-A, non-B hepatitis in children with acute leukemia and chronic liver disease.

Eleven children with acute lymphoblastic leukemia and chronic liver disease, who had negative reactions for hepatitis B virus markers in the liver, were studied at the time of therapy withdrawal for an antigen-antibody system linked to non-A, non-B (NANB) hepatitis infection. By immunofluorescence, six of the 11 children had a positive reaction for the NANB antigen in the liver, and five of these six children also had a positive reaction for the NANB antibody in serum. Histologic lesions were more severe in patients with the NANB antigen in the liver compared with those with a negative reaction.

Adolescent↗

Histological evidence of hepatitis-B-virus infection with negative serology in children with acute leukaemia who develop chronic liver disease.

A high percentage of patients with acute leukaemia in established remission develop chronic liver disease: how important hepatitis-B-virus (HBV) infection is as an aetiological factor is not clear. The presence of HBV markers in liver and serum of 23 leukaemic children with liver disease was investigated at the time of a diagnostic biopsy just before treatment withdrawal. Although, at this time, none had HBV antigens or antibodies in the serum by radioimmunoassay, HBsAg was detected by direct immunofluorescence in the cytoplasm of hepatocytes in 13 children, 7 of whom also had hepatitis-B core or e antigens in hepatocyte nuclei. This pattern of both cytoplasmic and nuclear fluorescence was present in 4 of 6 patients with the histological features of chronic active hepatitis on liver biopsy. The failure of release of viral antigens into serum and the absence of an adequate immune response were probably due to the intense chemotherapy used to induce and maintain remission, since HBV markers appeared in the serum within 15 months of stopping treatment in 8 of the children in whom viral antigens had been detected in liver tissue but in none of those whose biopsy specimens were negative by immunofluorescence. These results suggest that HBV infection may be an important cause of chronic liver disease in children with leukaemia and show that during treatment serological tests may fail to detect the presence of the virus.

Adolescent↗

Chemotherapy does not affect the development of inter-Sertoli junctions in childhood leukaemia.

The inter-Sertoli junctions of children aged between 5 and 12 years, affected by acute lymphoblastic leukaemia, were analyzed in sections and freeze-fracture replicas. The testicular biopsies were performed at the end of therapy, when patients were in continuous remission for over 30 months. Chemotherapy does not seem to affect the development of junctions that were studied in sections and freeze fracture. Two age groups were considered (I, 5 to 8 years; II, 9 to 12 years). In age group I, oval Sertoli cells were connected by occasionally focal points of fusion, which in replicas appeared as scattered, interrupted ridges on the P face and grooves on the corresponding E face. In age group II Sertoli cells presented cytoplasmic extensions and interdigitations. Tight junctions appeared close to one another in conventional sections. Freeze fracture evidenced extensive although isolated areas formed by intervining strands. Lanthanum penetrated freely the intercellular spaces and gap junctions were observed in both age groups. The results suggest that tight junctions formation is initiated long before puberty; a progression in the complexity of the strand organization is present as the tubules mature; the strands reorganize in parallel and continuous rows only at puberty.

Animals↗

Pharmacokinetics of VP16-213 given by different administration methods.

Plasma pharmacokinetics of VP16-213 were investigated after a 30-60 min infusion in 14 adult patients and six children. In adult the elimination half-life (T1/2 beta), plasma clearance (Clp) and volume of distribution (Vd) were respectively 7.05 +/- 0.67 h, 26.8 +1- 2.4 ml/min/m2, and 15.7 +1- 1.8 l/m2; in children 3.37 +/- 0.5 h, 39.34 +1- 6.6 ml/min m2, and 9.97 +/- 3.7 l/m2. After repeated daily doses no accumulation of VP16-213 was found in plasma. The unchanged drug found in the 24 h urine after administration amounted to 20-30% of the dose. In eight choriocarcinoma patients plasma levels of VP16-213 were measured after oral capsules and drinkable ampoules. The bioavailability compared to the i.v. route was variable, mean values being 57% for capsules and 91% for ampoules. In one further patient, with abnormal d-Xylose absorption results, VP16-213 was not detectable in plasma after the oral ampoule dose. Steady state levels investigated in three patients after 72 h continuous VP16-213 infusion (100 mg/m2/24h) were around 2-5 micrograms/ml. Levels of VP16-213 were undetectable in CSF after i.v. or oral administration.

Administration, Oral↗

Evaluation of the supertransfusion regimen in homozygous beta-thalassaemia children.

The maintenance of physiological levels of haemoglobin is beneficial in the management of patients with thalassaemia major since it leads to better tissue oxygenation, reduction of blood volume, and reduced intestinal absorption of iron. We have studied 11 patients with thalassaemia major while treating them for 4-12 months with a standard transfusion regimen (mean pre-transfusion Hb 10.2 g/dl) and then for a second period of 7-18 months with a supertransfusion regimen (mean pre-transfusion Hb 12.3 g/dl). Blood consumption was 16.71 +/- 2.0 ml/kg/month in the first period; it rose to 20.30 +/- 3.5 ml/kg/month in the first 5 months of the second period, and then returned to the values of the first period (16.53 +/0 2.0 ml/kg/month). There were no significant differences in blood consumption between the two transfusion regimens, after the 5-month equilibration period.

Adolescent↗

Haemoglobin levels and blood requirement in thalassaemia.

The relationship between blood requirement and the mean level of maintained haemoglobin was examined in 392 patients with homozygous beta-thalassaemia. Pre- and post-transfusional haemoglobin levels and the amounts of blood transfused were measured during a 1-year period. No significant differences were noted in the blood requirements of patients (splenectomised or not) irrespective of the haemoglobin level. It may be supposed that if the mean haemoglobin level is high the haematopoietic activity is inhibited, and hence the bone marrow mass and total blood volume are reduced. High haemoglobin levels may thus be obtained with no increase in blood intake.

Adolescent↗

Long-term survival in childhood acute lymphocytic leukemia in Italy.

Among 727 children with acute lymphocytic leukemia (ALL) observed at eight pediatric clinics in Italy in the years 1967-1974, 200 (27.5%) survived for more than five years after diagnosis. The proportion of long-term survivors rose significantly during the years 1970-1974 when aggressive therapeutic programs with curative intent were uniformly adopted in Italy (19.8% vs. 29.4%; P less than 0.05). Clinical and laboratory data at diagnosis of the 200 long-term survivors were analyzed and compared with that of the 527 nonsurvivors. We found that, besides a leukocyte count greater than 50,000 cells/mm3, other factors such as early central nervous system CNS leukemia and the presence of mediastinal mass were predictive of a poorer prognosis for long-term survival. Life-table analysis revealed that the chance of long-term survival was significantly higher in those children who have survived for five years without relapse (82.9% vs. 24.1%; P less than 0.01). Although late initial relapse is always possible, if a child with ALL remains in continuous complete remission for at least nine years, it is likely that the patient is cured.

Adolescent↗