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Biomedical subjects

C Belloni

Publications and source records attributed to C Belloni.

At least 19 recordsLinked to original sources

Low prevalence of islet autoantibodies in patients with gestational diabetes mellitus.

OBJECTIVE: To determine the proportion of patients with gestational diabetes mellitus (GDM) who have serological characteristics typical of IDDM. RESEARCH DESIGN AND METHODS: Islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD65, and IA-2 antibodies were measured in 145 pregnant women with GDM, 33 with impaired glucose tolerance (IGT), and in 73 with normal glucose tolerance (NGT). ICAs were measured by indirect immunofluorescence; GAD65 and IA-2 antibodies, by a radio-ligand immunoassay incorporating 35S-labeled recombinant antigen; and IAAs, by a liquid-phase radiobinding assay. RESULTS: The prevalences of islet autoantibodies were low and not significantly different between groups. ICAs were detected at levels ranging from 5 to 45 Juvenile Diabetes Foundation U in 14 (10%) women with GDM, 2 (6%) women with (GT, and in 4 (5%) women with NGT. IAAs were detected at levels between 3 and 4 SD above the mean in 4 (3%) women with GDM, 0 women with IGT, and in 1 (1%) woman with NGT. None had both ICAs and IAAs. Neither GAD65 nor IA-2 antibodies, which have been detected in the majority of pre-IDDM and IDDM patients, were found in NGT, IGT, or GDM patients. CONCLUSIONS: Low-titer ICAs and IAAs are not infrequent in pregnant women, but multiple islet autoantibodies and antibodies to GAD65 or IA-2 were not found in GDM. These findings suggest that the serological characteristics of IDDM are rare in GDM.

Adult

Postnatal variations of growth hormone bioactivity and of growth hormone-dependent factors.

OBJECTIVE: To evaluate whether the low insulinlike growth factor I (IGF-I) levels that are observed in the neonate depend on the biological inactivity of the molecular forms of growth hormone (GH) or on the immaturity of the hepatic GH receptors during the early postnatal period. MATERIALS AND METHODS: Serum samples were collected from 60 normal full-term neonates on day 5 and at 1 and 4 months of age to evaluate the GH concentrations by using both an immunofluorometric assay and Nb2 cell bioassay, as well as the GH-binding protein, IGF-I, and IGF-binding protein 3 values by radioimmunoassay. RESULTS: Five-day-old neonates showed significantly higher (P < .001) mean +/- SEM GH levels that were measured by using the immunofluorometric assay (27.22 +/- 1.62 micrograms/L) and Nb2 cell bioassay (3.56 +/- 0.14 U/mL) compared with those levels in 11 prepubertal children who were studied as control subjects (1.26 +/- 0.28 micrograms/L and 0.74 +/- 0.08 U/mL, respectively). At 1 and 4 months of age, GH values that were measured by using both the immunofluorometric assay (9.15 +/- 0.89 and 2.58 +/- 0.32 micrograms/L, respectively) and Nb2 cell bioassay (2.52 +/- 0.11 and 1.71 +/- 0.15 U/mL, respectively) were decreased significantly (P < .001). In 5-day-old neonates, we observed significantly lower (P < .001) serum GH-binding protein (9.73% +/- 0.42%), IGF-I (67.63 +/- 5.20 ng/mL), and IGF-binding protein 3 (1.46 +/- 0.17 mg/L) concentrations compared with those in the prepubertal children (30.74% +/- 2.01%, 210 +/- 25 ng/mL, and 3.08 +/- 0.22 mg/L, respectively). At 1 month of age, serum GH-binding protein (16.00% +/- 0.70%) and IGF-binding protein 3 (2.96 +/- 0.30 mg/L) values were increased significantly (P < .001), while IGF-I levels (72.55 +/- 7.6 ng/mL, P = .09) were not increased. Serum IGF-I values were increased significantly (P < .005) at 4 months of age (97.94 +/- 9.68 ng/mL). CONCLUSION: The interaction of bioactive molecular forms of GH with the increased hepatic GH receptors induces the rise in postnatal IGF-I levels in early infancy.

Age Factors

Prevalence of fetal left ventricular hyperechogenic foci in a low risk population.

OBJECTIVE: To ascertain the prevalence and clinical significance of small hyperechogenic foci detected in the fetal left ventricle in routine ultrasound screening of pregnant women attending our hospital. POPULATION AND METHODS: From April 1994 to April 1995, 1135 consecutive pregnant women examined at the obstetric ultrasound unit of our hospital were studied prospectively. A postnatal cardiologic examination was performed when signs of cardiopathy were observed at the prenatal ultrasound investigation or the neonatal examination. RESULTS: Congenital heart disease was detected in 10/1148 infants born (0.9%); eight diagnoses were made prenatally (detection rate 80%). The prevalence of left ventricular hyperechogenic foci was 3.2% (37/1148 fetuses). In 35 cases (94.6%) the foci were no longer observed at the routine third trimester examination. Only in two cases (5.4%) did foci persist at the postnatal examination but without clinical signs of cardiopathy or karyotype anomalies. No association was observed between foci and major structural abnormalities. The foci were single in 32 cases (86.5%). Four foci (10.8%) were located at the interventricular septum, five (13.5%) bilaterally at the papillary apparatus of the mitral valve, and the others at the ventricular wall. No focus was associated with incompetence of the affected valve, whereas five (13.5%) were associated with a fetal disorder. CONCLUSIONS: The prevalence of intracardiac hyperechogenic foci in our general population considered at low risk was more than five times greater than that reported in the literature. Foci were not associated with structural heart defects or chromosomal abnormalities. Persistence during the third trimester and postnatal life was rare and without evident signs of heart disease.

Cardiomyopathies

Insulin antibodies do not preclude optimization of metabolic control in women with IDDM during pregnancy.

OBJECTIVE: To evaluate whether the presence of insulin antibodies (IAs) may preclude the optimization of metabolic control during pregnancy and affect outcome in women with IDDM. RESEARCH DESIGN AND METHODS: IAs were measured by radiobinding assay in 44 women with IDDM referred to the Diabetes and Pregnancy Outpatients' Clinic during 46 pregnancies. Age, duration of IDDM, metabolic control (HbA1c, mean pre- and postprandial capillary blood glucose, frequency of hypo- or hyperglycemia), insulin requirement at 1st and 3rd trimester of pregnancy, BM1, and weight gain were recorded. Neonatal variables such as gestational age, weight, length, and the presence at birth of either hypoglycemia, hypocalcemia, or jaundice requiring phototherapy were also considered. RESULTS: IAs correlated positively with insulin requirement (P < 0.05) and negatively with HbA1c at term (P < 0.01). Patients with IA levels > or = 40% insulin binding (8 of 46) had a higher insulin requirement and lower preprandial capillary blood glucose at the beginning of pregnancy but not at term (P < 0.005), whereas they had lower HbA1c at term than did patients with low IA levels (P < 0.01). IA levels decreased slightly at term (P = 0.007). IA levels > or = 40% were not associated with a higher rate of hypo- or hyperglycemic episodes or with diabetic complications or thyreopathy. No correlation was found between 1A levels and any of the neonatal variables considered. CONCLUSIONS: The presence of IAs does not preclude optimization of metabolic control during pregnancy and is compatible with a favourable outcome.

Adult

Anti-HBV neonatal immunization with recombinant vaccine. Part I. Critical appraisal for a long-lived antibody course.

This study involved 912 infants born to HBsAg-negative mothers from 1 May 1991 to 30 June 1992. The subjects were randomly allocated to an accelerated (Group A) or traditional (Group B) immunization schedule and immunized with 10 micrograms of recombinant HBV vaccine. At the end of the vaccinal cycle 98.14% of both groups were protected against HBV with a high percentage of high responders (88.1% group B and 68% group A). Following a random plan, 345 of the initial 912 infants (144 group A and 201 group B) were serologically evaluated, 15-18 months after the booster dose, to identify the level of long-lasting specific antibody. The data obtained allowed us to identify the non-responder subjects after the seroconversion, to propose the evaluation of antibody titre after the booster dose of vaccine and, because one year after the booster dose 5.6% of the subjects responsive at seroconversion have shown undetectable anti-HBsAg titre, to propose the elevation of the antibody level considered as protective at the end of the vaccinal cycle.

Hepatitis B

Anti-HBV neonatal immunization with recombinant vaccine. Part II. Molecular basis of the impaired alloreactivity.

HLA study was performed in 9 absolute non-responder (serum titre of anti-HBsAg < 2 mIU ml-1) and 8 hyporesponder (serum antibody level between 2 and 9.9 mIU ml-1) babies who underwent, in neonatal period, HBV vaccination with Engerix B recombinant vaccine. The investigation pointed out that many of these subjects carry HLA haplotypes classically involved in autoimmune diseases: namely HLADR7; DQ2, DR4; DQ8 and DR3; DQ2. The genomic typing for DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 genes revealed an increased frequency of the DRB1*0701; DQA1*0201; DQB1*0201 haplotype (23.5 vs 9.9% of the controls) and of DPB*0201 allele (42.3 vs 13.2% of controls). The polymorphism of Bf, C4A and C4B complement serum components, recognized as important "immune-function-related genes", pointed out an increased frequency of the null allele C4AQ0 (34.3 vs 6.8% of the controls) stressing the role of C4A serum complement component in response to foreign peptide. The immunogenetic investigation has been extended to 23 responder babies (titre of anti-HBsAg > 50 mIU ml-1), vaccinated with the same trial as the poor responders. The HLA frequencies observed in this group were comparable to those of control population and, with respect to the HLA markers cited above, absolutely different from the non/hyporesponder infants. From the HLA class II sequence analysis in the group of poor-responder babies some characteristics, peculiar to autoimmune diseases, have been observed: the majority of the infants showed at least an arginine at the 52 residue of the alpha chain of DQ molecule and a non-aspartic acid at the 57 position of the DQ beta chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles

Heterogeneous IgG subclass distribution of islet cell antibodies.

Islet cell antibodies (ICA)-IgG are the serological marker of type 1 diabetes, an organ-specific autoimmune disease. A proportion of patients also have thyro-gastric autoimmunity, implying a broader humoral autoreactivity in these cases. In order to determine whether this is also reflected within islet cell antibodies (ICA) we examined the ICA-IgG subclass distribution in type 1 diabetic patients with or without associated thyro-gastric autoantibodies. ICA-IgG subclasses were detected by two-step indirect immunofluorescence, using monoclonal antibodies against the four IgG subclasses, in sera from 51 patients with type 1 diabetes and detectable ICA; 31 had no other antibodies (group 1) and 20 had at least one associated thyroid and/or gastric autoantibody (group 2). Our results show that ICA are polyclonal and invariably IgG1. In 48% of patients with type 1 diabetes without associated thyro-gastric autoantibodies, ICA were restricted to IgG1 only. Conversely, only 10% of those with thyro-gastric antibodies had ICA-IgG1 only (P < 0.02), and a larger ICA-IgG subclass recruitment was observed in these patients (P = 0.002). These findings provide evidence of heterogeneity within ICA at the IgG subclass level, with a broader clonal recruitment within this specificity in individuals displaying features of multiple organ autoimmunity. These results support the hypothesis of heterogeneity within the pathogenetic process leading to type 1 diabetes.

Autoantibodies

Estimating the depth of myometrial involvement by endometrial carcinoma: efficacy of transvaginal sonography vs MR imaging.

OBJECTIVE: In this study we compare transvaginal sonography with MR imaging for use in detecting the depth of myometrial involvement by endometrial carcinoma. SUBJECTS AND METHODS: Forty-two consecutive patients with stage I endometrial carcinoma had transvaginal sonography and MR imaging at 0.5 T. All the patients had a hysterectomy within 1-10 days after the imaging studies. The results of histologic examination of the surgical specimen were considered the gold standard of the study. We compared transvaginal sonography and MR imaging for use in assessing myometrial invasion by endometrial carcinoma by means of the staging classification of the International Federation of Gynecology and Obstetrics: stage Ia (tumor limited to endometrium), stage Ib (invasion of less than half the myometrium), stage Ic (invasion of more than half the myometrium). The overdiagnoses and the underdiagnoses for both techniques were calculated. We also evaluated the sensitivity and specificity of the two techniques for assessing the presence of myometrial invasion (stage Ib + stage Ic) and the presence of deep myometrial invasion (stage Ic). The diagnostic indexes evaluated and the differences between them were analyzed by using McNemar's test and 95% confidence intervals. The staging diagnoses based on MR imaging and sonographic findings were compared with staging diagnoses based on histologic examination, and a score was assigned to each diagnosis: these scores were then evaluated with Wilcoxon's signed rank test for paired data. RESULTS: Histologic examination showed that six of the 42 patients had tumor confined to the endometrium (stage Ia), 14 had involvement of the inner half of the myometrium (stage Ib), and 22 had involvement of the outer half of the myometrium (stage Ic). The staging was concordant between the two imaging techniques in 32 cases (concordance, 76%). Among the 10 discordant cases, diagnosis was correct in six cases for MR and four cases for sonography. Overall staging based on sonography was correct with respect to histologic staging in 29 cases (69%; 95% confidence interval, 52-81%). Five tumors (12%) were underdiagnosed and eight (19%) were overdiagnosed. Staging based on MR findings was correct with respect to histologic staging in 31 cases (74%; 95% confidence interval, 58-85%). Five tumors (12%) were underdiagnosed, and six (14%) were overdiagnosed. CONCLUSION: In our experience, there is no difference in the staging diagnoses of transvaginal sonography and MR imaging. Also, concordance with histologic staging diagnoses and sensitivity and specificity indexes did not show statistical differences between the two techniques, although these last results have to be considered with caution because of the low power of the statistical tests.

Adult

Control of hepatitis B: evaluation of two different vaccinal schedules in newborns from HBsAg negative mothers.

504 healthy infants, born to HBsAg negative mothers from May 1st to December 31st 1991, were randomly allocated to an accelerated (group A) or traditional (group B) immunization schedule. The group A infants were immunized at 4 days, 1 month and 3 months of life with 10 micrograms of recombinant HBV vaccine (Engerix B, SKF) while the group B infants were immunized at 4 days, 1 month and 6 months of life with the same dose of vaccine. One month after the first dose of vaccine, 9.2% of the infants in both groups had an HBsAb serum level > 10 mIU/ml. One month after the booster dose, at 4 months of life for group A and at 7 months for group B, 97.40% and 98.53% of the infants presented a serum level > 10 mIU/ml respectively. None in group A and only 2 patients in group B could be considered non-responders (serum concentration below 2 mIU/ml) and 4 infants in group A and 4 in group B were considered hypo-responders (serum level between 2.1 and 9.9 mIU/ml). Immunogenetic study performed on the 2 non-responders and 6 of the hypo-responders, revealed the presence in all but two of the HLA haplotypes, classically involved in the lack of hyporesponsiveness to foreign peptides, namely: HLA-DR7; DQ2, DR4; DQ3, DR15; DQ6 and DR3; DQ2. Surprisingly, 2 hypo-responders carried the HLA haplotypes (DR11, DQ7 and DR13, DQ6), usually associated with hyperresponsiveness. Both vaccinal cycles provided evidence that infants respond well to vaccination, started at birth, against hepatitis B virus with a high degree of protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin.

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3-5 days later by 100-150 micrograms of indium-111 streptavidin, at the specific activity of 280-370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1-8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1-30:1) and 45:1 (range 12:1-120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1-30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01-0.3) for recurrences and 0.05 for primary tumour (range 0.005-0.2). Over 24-48 h 14% i.d. (range 8-18% i.d.) was found in the urine, 14% i.d. (range 6-29% i.d.) in the blood and 63% i.d. (range 56-70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer.

Bacterial Proteins

Myometrial invasion by endometrial carcinoma: assessment with plain and gadolinium-enhanced MR imaging.

A prospective study was designed to determine the sensitivity and specificity of nonenhanced T2-weighted and contrast material-enhanced T1-weighted magnetic resonance (MR) imaging in assessing the depth of myometrial invasion in patients with proved endometrial cancer. In 56 consecutive patients with clinically determined early-stage disease, findings of the two MR imaging techniques were compared with results of histologic examination of surgical specimens. Myometrial invasion was classified as absent (stage IA), superficial (stage IB), or deep (stage IC). In the assessment of each tumor stage, the sensitivity and specificity of contrast-enhanced T1-weighted MR imaging were higher than those of non-enhanced T2-weighted MR imaging. In determining the degree of myometrial tumor invasion, the overall sensitivity of enhanced T1-weighted MR imaging was 87.5%, whereas that of nonenhanced T2-weighted MR imaging was 71.4% (P less than .05). The use of contrast material may improve the ability to assess, with MR imaging, the depth of myometrial invasion by endometrial cancer.

Adult

Neonatal B lymphocyte subpopulations and method of delivery.

We studied four groups of healthy term newborn infants: (1) 11 infants born by vaginal delivery; (2) 11 infants born by elective cesarean section; (3) 10 infants born by emergency cesarean section with labor, and (4) 10 infants born by complicated vaginal delivery. Total and differential leukocyte counts, cortisol blood level, and B lymphocyte subpopulations (SmIg, sIgD, sIgM, CD19, CD20, CD21, CD23) were evaluated in cord blood samples from the four infant groups. Furthermore, the Pentothal blood level was measured in infants born by elective cesarean section and in their mothers at delivery. Higher total and differential leukocyte counts and cortisol blood levels were observed in group 1 and 4 infants as compared with group 2 and 3 infants. A significant correlation was observed between cortisol blood level and leukocyte counts. The percentages of positivity to cell surface markers of B lymphocyte subpopulations were significantly higher in infants born by elective cesarean section. A negative significant correlation of thiopentone with sIgM and CD21 was observed. These data indicate a significant influence of method of delivery and of thiopentone on B lymphocyte subpopulations.

Analysis of Variance

Myometrial invasion by endometrial carcinoma: assessment by MR imaging.

In patients with early-stage endometrial cancer, preoperative knowledge of myometrial tumor extension has important prognostic and therapeutic implications. The purpose of this prospective study was to determine the sensitivity and specificity of MR imaging for assessing the depth of myometrial invasion in patients with endometrial cancer that clinically was thought to be confined to the uterine corpus. Sixty-five consecutive patients were included in the study. All patients had MR imaging before radical surgery. MR imaging findings were compared with microscopic pathologic findings in all cases. On MR images and at histologic analysis, myometrial invasion was classified as absent (tumor confined to the endometrium), superficial (less than 50% of myometrial thickness), or deep (50% or more of myometrial thickness). At histologic examination, tumor limited to the endometrium was proved in 14 cases, superficial myometrial invasion by tumor was present in 34 cases, and deep tumor invasion was demonstrated in 17 cases. In determining the presence of tumor confined to the endometrium, MR imaging had a sensitivity of 57% and a specificity of 96%. In the assessment of tumor with superficial myometrial invasion, MR imaging had a sensitivity and a specificity of 74%, whereas in assessing deep myometrial penetration, the sensitivity and specificity of MR were 88% and 85%, respectively. Errors in MR interpretation when determining myometrial tumor spread were more frequently overestimations rather than underestimations. Our results indicate that MR imaging is useful for the preoperative assessment of myometrial invasion in patients with proved endometrial cancer.

Adult

Neutrophil chemotaxis in infants delivered by caesarean section.

We evaluated polymorphonuclear leucocyte (PMN) chemotaxis and cortisol levels in cord blood from 15 healthy term infants delivered by caesarean section and from 15 healthy vaginally delivered term infants. Mean neutrophil chemotaxis was significantly higher in infants delivered by caesarean section (78.3 +/- 23.4 microns) than in vaginally delivered infants (57.8 +/- 16.6 microns; P = 0.01). Mean blood cortisol level was significantly lower in infants delivered by caesarean section (9.14 +/- 2.76 micrograms/dl) than in infants born by vaginal delivery (20.71 +/- 6.98 P = 0.0001). No relationship was found between PMN chemotaxis and blood cortisol level. The higher neutrophil chemotactic activity observed in infants delivered by caesarean section could be related to general maternal anaesthesia.

Anesthesia, General

Invasive cervical carcinoma: MR imaging after preoperative chemotherapy.

To evaluate assessment of tumor regression with magnetic resonance (MR) imaging, the authors studied 21 consecutive patients with cervical carcinoma tumors that were more than 3 cm in diameter. Thirteen of the 21 also demonstrated parametrial invasion. In all cases, MR imaging was performed both before and after chemotherapy. Pathologic specimens were obtained at hysterectomy in all patients. Comparison of pathologic and MR imaging findings after chemotherapy showed that all tumors decreased in size. Size of tumor was correctly determined at MR in 17 cases and was slightly overestimated in four cases. Five patients had residual parametrial invasion that was histologically confirmed. In detecting parametrial spread after treatment, MR imaging had an accuracy of 90.4%. Tumors had high signal intensity on T2-weighted images, whereas intratumoral necrosis was characterized by low signal intensity on the same images. Peritumoral inflammatory tissue found at pathologic examination in four of 21 cases was not specifically identified on MR images. In patients with invasive cervical carcinoma, MR imaging may be useful in evaluating tumor response to preoperative chemotherapy.

Adult

Carcinoma of the cervix: value of MR imaging in detecting parametrial involvement.

In patients with cervical carcinoma, precise knowledge of parametrial tumor extension affects the therapeutic decision between surgery and radiation therapy. The purpose of this prospective study was to determine the efficacy of MR imaging in detecting the presence or absence of parametrial invasion in patients with cervical cancer thought clinically to be confined to the cervix. Twenty-five consecutive patients were included in the study. All patients underwent radical hysterectomy or total abdominal hysterectomy and had detailed histologic evaluation of the parametrium. Ten had pathologic evidence of parametrial invasion; in the remaining 15, no parametrial invasion was identified pathologically. MR findings were compared with pathologic findings in all cases. For determining parametrial involvement, MR imaging had an accuracy of 88%, a sensitivity of 100%, and a specificity of 80%. Our results suggest that MR imaging is a reliable means of assessing parametrial invasion by cervical cancer.

Adnexa Uteri