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Biomedical subjects

F Morabito

Publications and source records attributed to F Morabito.

At least 73 records · Page 4Linked to original sources

Growth hormone treatment in adults with childhood onset growth hormone deficiency: effects on psychological capabilities.

The psychological aspects (personal traits, way of relating to the surrounding environment, perception of body image, degree of self-esteem) of eight adults with childhood onset growth hormone (GH) deficiency (GHD) were studied before and after 6 months of recombinant GH therapy. Each subject was evaluated using the following tests: the Bem Sex Role test, the non-verbal scales of the WAIS test for adults, the State-Trait Anxiety Inventory, the Experiential-World Inventory, the Image-Marking Method and the Draw-a-Person test; a psychoneurophysiological profile was also evaluated in order to monitor, by means of four neurophysiological variables (muscular tension, galvanic resistance, skin temperature and heart rate), the reactions to specific and aspecific stress. Before treatment, adults with GHD tended to underestimate their body size by an average of 30%, with peaks of 47% for the head area; furthermore, they showed a low level of self-esteem, a closed attitude towards social relationships, a pessimistic attitude with a tendency towards depression and a strong sense of detachment from the outside world. After 6 months of GH treatment, patients presented an overall improvement in relation to intellectual tasks, accompanied by a lower level of stress during their performance. A clear improvement was also observed in terms of emotional control during specific and aspecific stress, which might contribute a positive effect on their interrelationships. As expected, the treatment was not able to reduce the subjects' highly distorted perception of body image, due to the fact that GH treatment, despite a clear amelioration of lean/fat body mass ratio, did not change their body proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modulation of purine analogs- and chlorambucil-induced cytotoxicity by alpha-interferon and interleukin-2 in chronic lymphocytic leukemia.

The decrease in cell viability observed in vitro from the effect of chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxy-adenosine (CDA) on peripheral lymphocytes from 49 untreated CLL patients was investigated by the MTT colorimetric assay. The effects of recombinant-interleukin (r-IL)-2 and alpha-interferon (alpha-IFN) on drug-induced cell death were evaluated. r-IL-2 significantly increased in vitro resistance to CLB, while purine analog cytotoxicity was slightly reduced by the cytokine. The potential in vivo significance of r-IL-2, acting as a survival signal on CLB-induced cell death, is supported by the correlation between the lowest IL-2 serum levels, the highest in vitro sensitivity to CLB and a major clinical response after CLB treatment in six out of eight CLL patients. Using 25 samples, alpha-IFN enabled CLL cells to increase resistance to CLB, CDA and FAMP in 14, eight and seven samples, respectively; conversely, alpha-IFN showed a synergism with both CLB and FAMP in six samples and with CDA in four. These results correlate with immunoenzymatic assay data showing that alpha-IFN either up- or down-regulates tumor necrosis factor and IL-1 levels in supernatants of some CLL samples. Apparently, alpha-IFN plays a dual role in regulating drug-induced cell death, while IL-2 seems to solely favor cell survival in CLL.

Antineoplastic Agents↗

Comparison of younger versus older B-cell chronic lymphocytic leukemia patients for clinical presentation and prognosis. A retrospective study of 53 cases.

Fifty-three patients affected with B-cell chronic lymphocytic leukemia (CLL) younger than 50 years and observed in two hematological institutions have been retrospectively evaluated in order to verify whether this disease has different clinico-hematological features at presentation and different prognosis as compared to older cases. In our experience young cases with B-CLL diagnosis, confirmed by immunophenotype in 90.5% of patients, accounted for 7.1% of the whole CLL population. Sex distribution, mean peripheral lymphocyte count, platelet count, distribution among Rai's and Binet's stages, total tumor mass (TTM) score, histological pattern of bone marrow infiltration and lymphocyte doubling time (LDT) were similar to a series of 201 CLL cases older than 50 years. Only hemoglobin mean level was significantly higher in younger patients (13.1 +/- 2.1 vs 12.2 +/- 2.6 g/dl; p < 0.01). The overall median survival was 7.1 years. Rai and Binet staging classifications and TTM score system retained their prognostic value in this CLL population. In addition, cases fulfilling criteria of "smoldering" CLL, had a very long survival (75% survival probability at 16 years). Life-expectancy of younger patients was significantly longer than that of older ones (median survival, 7.1 versus 4.1 years; p < 0.05). However, when the background mortality due to non-CLL related deaths (i.e., cardiovascular complications, epithelial cancers) was removed, survival advantage of young cases disappeared. In conclusion this study confirms that prognosis of young CLL patients can be easily assessed using the current well-defined criteria. Since age is not by itself a criterion for intensifying treatment, further efforts to identify those young CLL patients who qualify for more aggressive therapy should be made.

Adult↗

[Blood prolactin patterns in hepatic cirrhosis].

Variations in PRL secretion were observed during chronic hepatic disorders. The aim of our study was to evaluate the behaviour of PRL in patients affected by hepatic cirrhosis. 6 patients (4 males and 2 females) were studied and matched with a group of healthy controls. In all subjects PRL values were evaluated in basal conditions and after TRH stimulation. The results obtained showed higher basal levels of PRL, together with higher and more prolonged TRH responses in patients with hepatopathies than in controls (p < 0.01). These abnormalities in PRL secretion during hepatic cirrhosis could be due to alterations of neurotransmitters at central level.

Aged↗

[The adult patient with a congenital GH deficiency. Cholesterol-lowering effects of therapy with biosynthetic GH].

In adults with childhood onset GH deficiency, serum total and LDL cholesterol levels were significantly higher (p < 0.05 and < 0.01, respectively), while serum HDL cholesterol levels were significantly lower (p < 0.05) than those recorded in an age and sex matched control group. These biochemical alterations determined the presence of a marked increase of coronary risk indexes (total/HDL cholesterol and LDL/HDL cholesterol) which were significantly higher (p < 0.0001) than in controls. Serum VLDL and triglycerides levels were similar to those found in controls. After recombinant GH treatment (0.5 IU/kg/week, sc), serum total and LDL cholesterol levels were significantly reduced, becoming similar to those recorded in controls after six months' therapy. Serum HDL cholesterol levels, which were slightly reduced after 3 months, significantly increased after 6 months of GH treatment, becoming similar to those recorded in controls; no significant modifications were observed in VLDL cholesterol and triglycerides levels during treatment. The coronary risk indexes fell during GH treatment, but still remained higher than in controls. On the basis of these promising data, it is tempting to speculate that more prolonged GH treatment might be able to ameliorate the risk for cardiovascular diseases in adults with GH deficiency. Although further additional studies with a larger number of patients are needed to confirm these preliminary observations, adults with GH deficiency should be recommended to take into great consideration the control of other risk factors involved in the genesis of coronary disease.

Adult↗

Galanin infusion partially restores the blunted growth hormone responses to repeated growth hormone releasing hormone stimuli in normal adults.

In order to understand the role exerted by the endogenous somatostatinergic tone in the blunting of GH responsiveness to repeated GHRH administration, we evaluated GH responses to the second GHRH bolus during a simultaneous infusion of galanin, which has been reported to inhibit the endogenous somatostatin release. Seven normal adults (3M/4F, age range 19-28 yr), admitted to the study after giving informed consent, were tested on three occasions, with a) two consecutive 1 micrograms/kg iv GHRH boluses administered at 0 min and 120 min, b) one GHRH bolus at 0 min followed by an infusion of 10 micrograms/kg bw galanin (diluted in 40 ml 0.9% NaCl) between 100 min and 140 min and c) two consecutive GHRH boluses (same dose and temporization of administration of test a) associated with a galanin infusion from 100 min to 140 min. GH responses were evaluated as the net incremental area under the curve (GH nAUC/h); all data were expressed as mean +/- SE. GH responses to the first GHRH bolus were similar in the three tests (mean GH nAUC, test A 990 +/- 80, test B: 1006 +/- 112, test C: 1077 +/- 80 ng/ml/h). In test A the second GHRH bolus was unable to sustain GH elevated levels (mean GH nAUC: 32 +/- 12 ng/ml/h vs first GHRH: 990 +/- 80 ng/ml/h, p < 0.0001). Similarly, in test B galanin infusion alone was unable to determine a clear GH rise (mean GH nAUC: -25 +/- 16 vs first GHRH: 1006 +/- 112 ng/ml/h, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth hormone treatment in adults with GH deficiency: effects on new biochemical markers of bone and collagen turnover.

Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of bone formation, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), marker of bone resorption, and aminoterminal propeptide of type III procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8 adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs 4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8 ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml, respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01) increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40 IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001) rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01) correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Melatonin response to TRH in prepubertal and pubertal healthy subjects.

The current study was carried out to evaluate the influence of thyrotrophin releasing hormone (TRH) on melatonin secretion in healthy subjects. The study included 31 subjects of both sexes (prepubertal subjects: 15; pubertal subjects: 16). They were treated with TRH (0.2 mg i.v. as a bolus) with blood samples being collected at 0, 20, 60, 120, 180 min. after hormone administration; the results were compared with those of subjects infused with saline only. Serum levels of melatonin were measured with a double antibody RIA method. A significant increase in melatonin levels after TRH was seen only in the prepubertal females, with a peak at 120 min. On the contrary, no significant melatonin changes were seen in the prepubertal males or in either pubertal males and females. These results suggest the existence of sex- and age-related differences in melatonin responses to TRH in humans.

Adolescent↗

Alpha 2-interferon in B-cell chronic lymphocytic leukemia: clinical response, serum cytokine levels, and immunophenotype modulation.

Fifteen patients with B-cell chronic lymphocytic leukemia (B-CLL) have been treated with alpha 2b-interferon (alpha IFN) for one year (3 mega units subcutaneously three times a week). The hematological response and the modulation of immunophenotype, serum levels of soluble interleukin-2 receptor (sIL-2R) and tumour necrosis factor (TNF) have been monitored. Hematologically 67% of cases were classified as responders, although no complete responses were observed; three cases progressed during treatment, and two patients showed stable disease. Both peripheral lymphocytes and CD24+ cell absolute number significantly decreased after twelve months of IFN treatment (40.7 +/- 17 x 10(9)/l versus 15.8 +/- 6 x 10(9)/l, mean values +/- sd, p < 0.01, and 30.4 +/- 5.5 x 10(9)/l versus 8.1 +/- 2.8 x 10(9)/l, p < 0.05, respectively), while CD24+ cell percentage did not change (72.1% +/- 4.6 versus 67.5% +/- 8.8, p not significant). In the majority of cases myelomonocytic markers (CD11c, CD14, CD11b) transitorily decreased during the treatment. Serum sIL-2R levels, elevated in all cases before IFN treatment, increased in responders. Serum TNF levels decreased in patients showing high values before the treatment. The explanation of these findings and their possible implication are discussed.

Aged↗

[Social integration in adulthood in a group of subjects with Turner syndrome].

The aim of the present study was to evaluate social integration in adulthood in a group of 48 subjects with Turner's syndrome. This was done by asking subjects to fill in a multi-choice questionnaire concerning their personal, social and working situation. The mean age (+/- SD) of the group was 24.8 +/- 1 and the reported stature was 142.2 +/- 1.4. The results obtained were compared with those formulated by ISTAT in 1990 for the entire Italian population. As far as regards education it was seen that 100% of subjects had completed primary school, 52% had attended secondary school, 29% had been to high school and 6% had attended university. It was therefore concluded that educational status, at least in this group, was higher than that of the Italian population in general. The cultural level of these subjects meant that most had found appropriate employment and only 6% were unemployed. 90% of the subjects were unmarried and only 5 were married (10%); the majority of those unmarried lived with their parents (83%). This underlines a prolonged dependence on the family nucleus and probable disorders regarding the subjects' own sexual identity and affective capacities. Among the parameters examined no substantial differences were found between subjects with a 45,X karyotype and those with chromosomic mosaicism. In the light of these findings it is apparent that efficacious medical and psychological strategies should be developed to enable a greater realization of interpersonal relations in the familial and social field.

Adult↗

[Melatonin secretion in Klinefelter's syndrome].

It has been observed that the pineal gland seems to modulate diencephalic neuroendocrine activity through its principal hormone, melatonin. In animals, melatonin inhibits the secretion and release of hypophyseal gonadotropins, probably by inhibiting hypothalamic releasing factors; in man, on the contrary, the administration of LHRH seems to have a stimulating effect on melatonin serum levels. In the light of this, in pathologies characterised by an imbalance in the hypothalamus-hypophyseal-gonad axis, it is possible to hypothesise variations in the secretion of melatonin and/or in its circadian fluctuations. In order to clarify further the relationship between the epiphysis and the hypothalamus-hypophyseal axis, the present study evaluated the pattern of melatonin secretion in a group of 16 patients with Klinefelter's syndrome. The circadian rhythm of melatonin secretion was determined from venous blood samples taken at 9 am, 1 pm, 5 pm, 9 pm, 1 am and 5 am; the same protocol was also followed in two control groups of respectively prepuberal and puberal healthy subjects. During the night samples were taken as rapidly as possible, using a red light source in order to not interfere with melatonin secretion. All of the examinations were performed during the winter period. Serum levels of melatonin were determined, after extractions with diethylether, by means of a double antibody RIA using commercially available kits (Bioscience Product--The Netherlands). Intra- and inter-assay coefficients of variation were respectively 3% and 8%. The data are reported as mean values +/- SD; the results were analysed by means of Student's test for unpaired data and analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The effect of GH on erythropoiesis in vivo].

It has been demonstrated that the direct and/or indirect stimulation of hematopoiesis is one of the effects of the growth hormone (GH) in vitro. In order to study the effect of GH on erythropoiesis in vivo, the variation of hemochrome in a group of 8 subjects with GH deficiency (GHD) were monitored during a substitutive therapy with biosynthetic GH (rhGH) at dose of 0.4 U/kg/week. Hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), number of red blood cells (RBC) were analysed in all subjects at the beginning and after 9 months of treatment. The effectiveness of therapy was demonstrated by statistically significant variations in height, height SDS, growth velocity, serum levels of IGF-I. After 9 months of rhGH therapy, a significant increase was observed in all values considered with exception of MCV. In conclusion Gh would appear to stimulate erythropoiesis, directly or indirectly, and these results would appear to indicate an in vivo confirmation.

Adolescent↗

Phenotypic and genotypic switch in Philadelphia-positive, BCR-positive blast crisis of chronic myeloid leukemia.

We report a case of Ph1-positive, bcr-positive chronic myeloid leukemia blast crisis (CML-BC) which at presentation showed a mixed myeloid/B-lymphoid immunophenotype along with TdT positivity and, at the molecular level, an oligoclonal rearrangement of the immunoglobulin heavy chain (IgH) gene region. After obtaining a successful remission, at the time of relapse the patient underwent a phenotypic and genotypic switch from mixed to myeloid phenotype, characterized by the loss of the lymphoid markers and TdT expression and by a germline configuration of the IgH gene region. The same bcr rearrangement was, however, found in both phases of the disease, supporting the suggestion of a true phenotypic and genotypic conversion. This report confirms that the neoplastic event in CML may take place at an early multipotent stem-cell level, prior to a well-defined phenotypic and genotypic lineage expression. Moreover, it is suggested that different factors (chemotherapy? growth factors?) may have either eradicated the bcr+/IgH+ clone and promoted the growth of bcr+/IgH- leukemic cells or, alternatively, supported the lymphoid differentiation program and induced a myeloid lineage shift.

Adult↗

Diagnostic and prognostic relevance of the immunophenotype in acute myelocytic leukemia.

The immunophenotype of 72 cases with acute myelocytic leukemia was investigated with a panel of monoclonal antibodies. When the morphologic criteria of the FAB classification was compared with the normal myeloid and erythroid pathway of differentiation identified by MoAbs, a relationship was found with FAB M5 and M6. Moreover, a constant negativity to HLA-DR and CD15 antigens in M3 and the contemporaneous expression of HLA-DR and CD11b antigens on the M4 and M5 leukemic cells were observed. We identified phenotypically distinct groups of patients with different responses to therapy. In fact, patients whose leukemic cells did not express the HLA-DR antigen showed, in a univariate analysis, a significantly higher percentage of complete remissions than did HLA-DR-positive patients. Multivariate discriminant analysis, in line with this result, showed that the parameters of discriminant capacity were, in order of statistical significance, young age, low WBC count and the lack of DR expression, respectively. A trend for a better response to therapy, without any statistical relevance, was also observed in CD11b-negative and CD33-positive cases. Similar results were detected in patients who expressed either DR or CD11b, or none of these markers. These findings indicate that immunophenotype may identify some FAB subtypes. Moreover, in some cases the phenotypic profile can provide useful information about the clinical outcome.

Adult↗

[Growth in stature in infantile-juvenile obesity].

The study aimed to assess the effect of juvenile simple adiposity on growth. The height (measured using a Hapenden stadiometer) of 1443 subjects (799 boys and 644 girls) aged from 6 to 16 was measured. The Quetelet index (QI) of adiposity was used; all subjects examined exceeded the 95th centile of the standard Cronk and Roche scale. Heights are expressed as standard deviation scores (SDS) and are compared to the British Standard. Adipose boys are taller than British boys up to the age of 12, then the difference lessens and the average heights of 15-year-old adipose boys are below the 50th centile of British growth charts. Female subjects showed a higher SDS from 6 to 8 years, after which the difference lessens gradually, and after 13 years the average height is below the 50th centile of British standards. Adipose boys are taller than normal boys during childhood; in prepuberty and puberty this difference lessens and during puberty they are shorter than British boys. This growth model is probably due to advanced skeletal maturity in adipose subjects with the result that at puberty growth lessens because it is exhausted. The wide epidemiological cross-sectional study confirms that growth is favourable in juvenile adiposity but does not alter adult height.

Adolescent↗