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Biomedical subjects

M Giovannini

Publications and source records attributed to M Giovannini.

At least 235 records · Page 13Linked to original sources
PubMed1992

Mother-to-child transmission of human immunodeficiency virus type 1: risk of infection and correlates of transmission.

One thousand eight hundred eighty-seven children born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers, including 1045 infants prospectively followed up from birth, were studied. Intravenous drug use was the most frequent maternal risk factor, although the percentage of women infected by sexual contact increased from 5.8% in 1985 to 28.5% in 1990. Of the 551 first children followed up from birth and older than 15 months of age, 101 (18.3%) acquired infection and seroconverted to HIV-1. Another 31 (5.6%) asymptomatic seronegative children showed the presence of viral markers, for an apparent mother-to-offspring transmission rate of 23.9%. Overlapping results were seen in 22 second-born children followed up from birth. Of 59 sibships with definite infection status, when the first child was infected, 14 (40%) of 35 second children were infected, whereas when the first child was not infected, only 2 of 24 (8.3%) second children were infected. Discordance in HIV-1 transmission was found in 1 of 18 pairs of twins. Univariate and multivariate analyses of possible risk factors for HIV-1 transmission performed on the entire population of children and in the cohort of those followed up from birth were basically in agreement in indicating that the development of symptoms in the mother before delivery and breast-feeding (indeed adopted in only 22 infants in whom HIV-1 infection was identified at birth) were significantly and independently associated with a higher transmission rate. In addition, girls were more frequently infected than boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗
PubMed1992

[Serum gastrin levels in colorectal cancers. Evolution after treatment].

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.

Adenocarcinoma↗
PubMed1991

[Kaposi's sarcoma in AIDS. 70 cases].

Although Kaposi's sarcoma is the most frequent of malignant diseases associated with AIDS and one of the first recognized manifestations of the syndrome, its management has not yet been standardized. This study concerns 70 AIDS patients with Kaposi's sarcoma followed up in the author's hospital department between june 1985 and december 1989. Most of these patients were homosexual or bisexual males. The mean time elapsed between the finding of a positive HIV test and the discovery of Kaposi's sarcoma was 15 +/- 3.2 months. Systematic evaluation disclosed visceral lesions in 50 percent of the patients. Chemotherapy was used in 55 cases, interferon-alpha in 23 cases and radiotherapy in 13 cases. The presence of visceral lesions clearly reduced survival time, although deaths were mainly due to opportunistic infections. Atypical forms of Kaposi's sarcoma sometimes make its diagnosis difficult, but the main problem is that of treatment, in view of the underlying immunodepression. The authors advocate the setting up of multicentre trials aimed at determining the best therapeutic approach in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Impaired GM-CSF production by cultured light density mononuclear cells and T lymphocytes correlates with the number of circulating CFU-gm in HIV-1 seropositive subjects.

The production of granulocyte/macrophage colony-stimulating factor (GM-CSF) by peripheral blood (PB) light density mononuclear cells (LD-MNC), CD2+ T lymphocytes and purified CD4+ T lymphocytes was investigated in 20 human immunodeficiency virus type 1 (HIV-1) seropositive (WRII-III) individuals in comparison with 18 normal controls. GM-CSF in supernatants of stimulated cultures was determined by biological and immunoenzymatic assays. GM-CSF production by LD-MNC, CD2+ T lymphocytes and purified CD4+ T lymphocytes was significantly (p less than 0.01) reduced in HIV-1 infected individuals, especially in patients at the more advanced stages of the disease. Moreover, the number of circulating granulocyte/macrophage colony-forming units (CFU-gm) was significantly (p less than 0.01) reduced in HIV-1 seropositive subjects (31.5 +/- 4.4) compared with normal controls (78 +/- 10). There was a positive correlation (r = 0.720, p less than 0.01) between CFU-gm and GM-CSF production by LD-MNC in HIV-1 seropositive individuals. On the other hand, the absolute number of CD4+ lymphocytes did not correlate with GM-CSF production by LD-MNC (r = 0.158) or CD2+ T lymphocytes (r = 0.225). These data indicate that the impaired production of GM-CSF in HIV-1-infected individuals is not only due to a reduction in CD4+ T lymphocytes, but also to a qualitative impairment of these cells which may contribute to the loss of circulating hematopoietic progenitors in HIV-1-infected subjects.

Adolescent↗
PubMed1991

Molecular characterization of PKU allele prevalent in southern Europe and Ireland.

A novel substitution has been characterized in the phenylalanine hydroxylase (PAH) gene that is linked exclusively to mutant haplotype 6, which is prevalent in southern Europe but rare in northern and eastern Europe. It is a G-to-A transition in intron 10, 11 bases from exon 11. This substitution creates an additional AG dinucleotide, which may serve as a cryptic splice acceptor site. Individuals who bear this substitution in the homozygous state have a severe PKU phenotype with pretreatment serum phenylalanine levels over 1200 mumol/liter. The frequency and distribution of this substitution among European populations suggests two possible founding populations, one being Middle Eastern and the other Roman. The use of this substitution as a marker to identify PKU chromosomes will be an invaluable aid to carrier screening and prenatal diagnosis in populations where mutant haplotype 6 is prevalent.

Alleles↗
PubMed1991

Phenylketonuria missense mutations in the Mediterranean.

Two missense mutations have been identified in the phenylalanine hydroxylase (PAH) genes of an Italian phenylketonuria (PKU) patient. Both mutations occurred in exon 7 of the PAH gene, resulting in the substitution of Trp for Arg at amino acid 252 (R252W) and of Leu for Pro (P281L) at amino acid 281 of the protein. Expression vectors containing either the normal human PAH cDNA or mutant cDNAs were constructed and transfected into cultured mammalian cells. Extracts from cells transfected with either mutant construct showed negligible enzyme activity and undetectable levels of immunoreactive PAH protein as compared to the normal construct. These results are compatible with the severe classical PKU phenotype observed in this patient. Population genetic studies in the Italian population revealed that both the R252W and the P281L mutations are in linkage disequilibrium with mutant restriction fragment length polymorphism (RFLP) haplotype 1, which is the most prevalent RFLP haplotype in this population. The R252W mutation is present in 10% and the P281L mutation is present in 20% of haplotype 1 mutant chromosomes. These mutations are both very rare among other European populations, suggesting a Mediterranean origin for these mutant chromosomes.

Base Sequence↗
PubMed1991

Reduced plasma C-20 and C-22 polyunsaturated fatty acids in children with phenylketonuria during dietary intervention.

The fatty acid composition of plasma and erythrocyte lipids was analyzed in 15 children with phenylketonuria (aged 3 to 12 years) during dietary treatment aimed to maintain plasma phenylalanine levels at less than 8 mg/dl (485 mumol/L), and compared with those of 12 matched control subjects. The diet of children with phenylketonuria provided less protein, with a very low proportion of animal proteins, less fat, but a higher proportion of linoleic acid as a percentage of calories, and a higher carbohydrate content versus that in the diet of control subjects. The children with phenylketonuria had higher plasma levels of oleic acid but lower levels of arachidonic (n-6) and n-3 fatty acids. Linoleic and eicosatrienoic (n-9) acid levels were the same in both groups. These changes in patients with phenylketonuria resemble those observed in vegetarians and may be due to the absence of preformed arachidonic acid and long-chain n-3 fatty acids in the phenylketonuric diet.

Child↗
PubMed1991

Elevated serum gastrin levels in patients with colorectal neoplasia.

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.

Adenocarcinoma↗
PubMed1991

Effect of human immunodeficiency virus type 1 on CD34+ cells.

The effect of HIV-1 on the in vitro growth of enriched hematopoietic stem cells (CD34+ cells) obtained from normal peripheral blood samples was studied. In comparison to untreated controls, the number of viable CD34+ cells progressively and significantly decreased in liquid cultures containing interleukin-3 (IL-3, 100 U/ml) after inoculation with HIV-1. In inoculated samples there was a significant reduction of all the hematopoietic progenitors (CFU-GM, BFU-E, CFU-Meg) starting from the second day of culture, CFU-GM being the most affected. In spite of these findings, no evidence of viral replication was observed: the total amount of p24 in HIV-1-inoculated CD34+ cell cultures showed a plateau, slightly declining towards the end of the experimental observation period. Moreover, erythroid and granulomacrophage colonies harvested from inoculated CD34+ cell cultures were unable to infect susceptible cells.

Antibodies, Monoclonal↗
PubMed1991

Evidence for an HIV-1 mediated suppression of in vitro growth of enriched (CD34+) hematopoietic progenitors.

The effect of HIV-1 on the in vitro growth of CD34+ cells, purified from bone marrow of normal donors, was studied. HIV-1 treated CD34+ cells exhibited a progressive and significant decrease of cell viability in liquid cultures and a reduced percentage of committed progenitors in the absence of viral infection. The same results were obtained treating CD34+ cell cultures with recombinant gp 120 alone. These results point to a direct cytotoxic activity of gp120 for CD34+ cells.

Antigens, CD↗
PubMed1991

HIV-1 infection and hematologic picture.

This review examines the wide spectrum of hematological abnormalities frequently observed in the peripheral blood and bone marrow of HIV-1 infected subjects. Several pathogenetic mechanisms have been implicated in the derangement of the hematopoietic system occurring during the course of HIV-1 infection: imbalance of the T-cell subpopulation (CD4/CD8 ratio), altered cytokine production by infected CD4+marrow cells, production of inhibitory factors by infected marrow stromal cells, antibody-mediated suppression of hematopoietic progenitors, direct infection of hematopoetic progenitors and/or precursors, and HIV-1 mediated suppression of CD34+ cell growth in the absence of a complete viral replication cycle. Each point is considered in the text, with particular attention to the mechanisms most likely to operate in the early stages of the syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Cancer of the rectum. Results of a prospective study comparing preoperative rectal touch and transrectal ultrasonography with postoperative histopathology before and after preoperative radiotherapy].

Between January 1988 and December 1990, 23 patients with rectal cancer were evaluated by clinical staging (23) and transrectal sonography before (22, one complete stenosis) and after radiotherapy (21). Two criteria were correlated with histological findings: a) the confinement to the rectal wall or spread beyond and b) the presence of meso-rectal lymph node involvement. The 22 patients who underwent transrectal sonography before radiotherapy were staged as uT2: 3 cases, uT3: 17 cases and uT4:2 cases. Fifteen days after irradiation, transrectal sonography showed a regression on the tumor in all cases; the uT stage was different in 9 patients but there was no change in the uN stage. The comparison of the preoperative clinical and sonographic assessment of local invasion beyond the rectal wall with postoperative histopathology revealed a correlation: a) with digital examination in 13 of the 21 patients with palpable tumors, b) with transrectal sonography before irradiation in 12 of the 22 staged tumors, c) with transrectal sonography after irradiation in 17 of the 21 staged tumors. The presence of meso-rectal lymph node involvement determined by histologic examination was correlated with the results of transrectal sonography for 14 of the 21 staged tumors. Transrectal sonography provides a good assessment of the tumor stage before irradiation. This stage should be considered for the study of survival.

Adenocarcinoma↗
PubMed1990

Inoperable nonmetastatic squamous cell carcinoma of the esophagus managed by concomitant chemotherapy (5-fluorouracil and cisplatin) and radiation therapy.

Thirty-five patients with nonmetastatic squamous cell carcinoma of the esophagus were treated with chemotherapy (5-fluorouracil, cisplatin) and concomitant split-course radiation therapy. All of the patients presented with dysphagia. Treatment consisted of two courses of chemotherapy with 5-FU (1 g/m2/day in continuous infusion for 5 days [days 1 to 5 and days 29 to 33] ) and cisplatin (70 mg/m2 intravenous bolus at days 2 and 30). Radiation therapy was concomitant in two courses delivering 20 Gy in 5 days (days 1 to 5 and days 29 to 33). On the first day of treatment, endoscopic peroral dilation or Nd-YAG laser therapy was usually carried out. At the end of the treatment, all of the patients were capable of oral nutrition. Histoendoscopic confirmation was made 8 weeks after the beginning of the therapy. Twenty-five of the 35 patients had a complete response with negative biopsy findings. There was only one serious complication (fatal myelosuppression) in the only patient who received more than two courses of chemotherapy. Sixteen patients died and 19 were still alive at 3 to 42 months after the beginning of treatment. Overall median survival for the 35 patients is 17 months. Actuarial survival was 55 +/- 18% at 1 year and 41 +/- 21% at 2 years. The median survival of the Stage I and II patients is 28 months. These results confirm that concomitant chemoradiotherapy is capable of producing a very high histoendoscopic complete response rate and improved 1-year and 2-year survival. The use of concentrated split-course radiotherapy enabled the authors to reduce the total length of the treatment to two periods of 5 days, with results that are similar to previous studies using classic radiotherapy for a 5-week to 7-week period.

Adult↗