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Biomedical subjects

M Baldini

Publications and source records attributed to M Baldini.

At least 37 records · Page 2Linked to original sources
PubMed1999

A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E.

Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q31.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair -159 from the major transcription start site (CD14/-159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were significant only among children who were skin test-positive to local aeroallergens (P = 0.004). There was no association between CD14/-159 and either interleukin (IL)-4 or interferon (IFN)-gamma responses by peripheral blood mononuclear cells. However, IFN-gamma and IL-4 responses were positively and negatively correlated, respectively, with serum sCD14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels and total serum IgE levels.

Base Sequence↗
PubMed1998

Neurotoxicity of interferon-alpha in melanoma therapy: results from a randomized controlled trial.

BACKGROUND: The objective of this study was to evaluate the neurologic and quality of life impact of low dose adjuvant interferon (IFN)-alpha immunotherapy in patients with malignant melanoma metastatic to regional lymph nodes after radical surgery. METHODS: One hundred and thirteen patients were randomized to receive IFN-alpha, 3 x 10(6) IU three times weekly by subcutaneous injection for 36 months or until melanoma recurrence (IFN group), or to act as controls (CTR group). Seventy-five of these patients (66%) entered the toxicity study and underwent formal neurologic, neuropsychologic, psychologic, and quality of life assessments. Patients were assessed at baseline and after 1, 3, 6, and 12 months of follow-up. For each variable, maximum worsening of symptoms from baseline was considered as a response variable. The differences between the two groups regarding this variable were evaluated by means of the Hodges-Lehmann median unbiased point estimates and their 95% confidence interval. RESULTS: A significant degree of action tremor was found in eight patients in the IFN group and in none of the controls. No differences were found during psychiatric evaluation and for cognitive tests. There was a greater increase in anxiety in the IFN group on both trait and state anxiety. With regard to quality of life the analysis showed a significant worsening of at most one level on only three questionnaire items and on the fatigue scale. CONCLUSIONS: Neurologic dysfunction associated with IFN therapy was mild. Psychiatric symptoms and neuropsychologic impairment were not found. Levels of fatigue and anxiety were increased in the IFN group but without a sizable impact on quality of life measures.

Adult↗
PubMed1998

Linkage of circulating eosinophils to markers on chromosome 5q.

Although peripheral blood eosinophilia is strongly associated with the risk of developing asthma, genetic determinants of eosinophilia have not been extensively studied. We used sib-pair analysis to assess linkage of circulating eosinophils (as a percent of total white blood cells [WBC]) to nine markers located in chromosome 5q31-33. The study was divided into two phases. Of 246 sib pairs available for the first phase, 35 were classified as low concordant (LC) (both sibs had <= 2% circulating eosinophils), 18 were defined as high concordant (HC) (both sibs had 5% or more circulating eosinophils), and 26 were defined as discordant (one sib had <= 2% and the other sib had 5% or more circulating eosinophils). Significant evidence for linkage among low concordant sib pairs was found for several markers in the region under study, with a peak for marker D5S500 (proportion of alleles shared identical by descent [ibd] = 0.68 +/- 0.05 [mean +/- SE], p = 0.0004). A cross-validating study was done in which an additional 19 sib pairs that were low concordant for circulating eosinophils were studied. Evidence for linkage was also observed in this subset. Results were independent of current wheezing, total serum IgE levels, and other potential confounders. A multipoint analysis done for all low-concordant sib pairs available showed that the maximal logarithm of the odds favoring genetic linkage (LOD) score (2.4, p = 0.0004) was observed in correspondence with marker D5S658. We conclude that a locus or loci may be present in chromosome 5q31-33 that controls for circulating eosinophils as a proportion of total WBC.

Alleles↗
PubMed1997

Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

The beta2-adrenergic receptor (beta2AR) agonists are the most widely used agents in the treatment of asthma, but the genetic determinants of responsiveness to these agents are unknown. Two polymorphic loci within the coding region of the beta2AR have been recently described at amino acids 16 and 27. It has been reported that glycine at codon 16 (Gly-16) is associated with increased agonist-promoted downregulation of the beta2AR as compared with arginine-16 (Arg-16). The form of the receptor with glutamic acid at codon 27 (Glu-27), on the other hand, has been shown to be resistant to downregulation when compared with glutamine-27 (Gln-27), but only when coexpressed with Arg-16. To assess if different genotypes of these two polymorphisms would show differential responses to inhaled beta2AR agonists, we genotyped 269 children who were participants in a longitudinal study of asthma. Spirometry was performed before and after administration of 180 microg of albuterol, and a positive response was considered an increase of >15.3% predicted FEV1. There was marked linkage disequilibrium between the two polymorphisms, with 97.8% of all chromosomes that carried Arg-16 also carrying Gln-27. When compared to homozygotes for Gly-16, homozygotes for Arg-16 were 5.3 times (95% confidence interval 1.6-17.7) and heterozygotes for beta2AR-16 were 2.3 times (1.3-4.2) more likely to respond to albuterol, respectively. Similar trends were observed for asthmatic and nonasthmatic children, and results were independent of baseline lung function, ethnic origin, and previous use of antiasthma medication. No association was found between the beta2AR-27 polymorphism and response to albuterol. These results may explain some of the variability in response to therapeutic doses of albuterol in children.

Adrenergic beta-Agonists↗
PubMed1997

Thyroid vascularization by color doppler ultrasonography in Graves' disease. Changes related to different phases and to the long-term outcome of the disease.

To investigate possible correlations between thyroid vascularization and activity of Graves' disease, we measured blood flow (TBF) at the inferior thyroid artery and intraparenchymal vascularization (number of vessels per square centimeter) by color Doppler ultrasonography (CDU) on Graves' patients at different phases of the disease. We studied 88 patients cross sectionally: 22 untreated; 17 euthyroid after 6 months of methimazole; 49 euthyroid at drug withdrawal after 12 to 24 months of treatment. The patients of the latter group were followed up for 29.1 +/- 6.3 months after discontinuation of treatment. On the day of CDU examination, free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), antiperoxidase and anti-TSH receptor (TRAb) antibodies were measured. Vascularization indices were significantly higher in the Graves' patients than in controls. In the patients euthyroid under treatment, vascularization was not significantly lower than in the untreated group, but TBF and vessel number both appeared clearly reduced in the patients tested at drug withdrawal. The vascularization indices at drug withdrawal were significantly higher in the patients who relapsed than in those in stable remission: TBF (mL/min) 50.6 +/- 36.8 vs. 23.8 +/- 17.5, p = 0.001; vessel number/cm2 1.8 +/- 0.8 vs. 0.8 +/- 0.5, p = 0.002. A multivariate analysis, evaluating the predictive value of vascularization, hormonal and immunological parameters for relapse, demonstrated a significant predictive value for TRAb (RR 8.2; p = 0.001) and a weak predictive value for TBF (RR 1.1; p = 0.02). In conclusion, CDU examination confirms that thyroid hypervascularization in Graves' disease is not related to thyroid hormone circulating levels. The association of increased TBF and high levels of TRAb in the relapsing forms of disease suggests that thyroid hypervascularization is probably related to the activity of the underlying autoimmune processes.

Adult↗
PubMed1996

[Not Available].

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Greece↗
PubMed1996

[Serum lactate-dehydrogenase isoenzymes in HIV positive children. A longitudinal study].

The impairment of humoral immunity with rapid turn-over of cellular B clones in children with HIV infection is known as well as the conduct of LDH isoenzymes in B cell lymphoproliferative diseases like Burkitt's lymphoma. Therefore, serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its isoenzymes have been evaluated twice (within 12 months) in 11 children with HIV infection with respect to a control group (30 subjects). Furthermore, the relationship between those and other clinical and immunologic parameters (total lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta CDC 1987) has been studied. HIV infected children have shown a significant decrease in LD1 rates, which was directly correlated to CD4/CD8 values. After the follow-up, this correlation became even more significant. Thus, these findings may suggest the usefulness of LDH isoenzymes evaluation as a marker of disease activity in children with HIV infection.

Antibody Formation↗
PubMed1995

Acute traumatic posterior fossa subdural haematomas.

Acute Posterior Fossa Subdural Haematoma (PFSDH) caused by trauma is a clinical rarity: only 13 cases have been encountered in the literature. Three consecutive personal cases of PFSDH are presented. Two of them are respectively the sixth and the seventh surgically treated cases with success. Among the 16 cases 60% had a sudden clinical worsening within 24 hours. Seven cases had an occipital fracture. Of the thirteen cases operated upon 11 (85%) were in a state of deep coma. The surgical mortality was 46%. One patient had a good recovery (Grade 5) and six a moderate disability (Grade 4) on the Glasgow Outcome Scale. We conclude that surgical treatment must always be carried out even in patients presenting in an agonal state.

Adolescent↗
PubMed1995

Human lymphocyte antigens in Graves' disease: correlation with persistent course of disease.

Graves' disease is a thyroid autoimmune disorder associated with specific human lymphocyte antigen (HLA) alleles, characterized by an unpredictable long-term course. To investigate possible relations between HLA phenotype and outcome of the disease, the authors typed for HLA antigens in 105 patients with Graves' disease with different course of disease. All patients were treated with antithyroid drugs for at least 12 months; 29 patients had stable remission 24 or more months after withdrawal of treatment; 76 patients had persistent disease--66 unremitting/relapsing hyperthyroidism, 10 stable hypothyroidism--36 or more months after onset of disease. The following findings emerged from this study: 1) HLA B8 and DR3 were increased significantly in Graves' patients versus 6,682 control subjects from the same geographic area (23.80% vs 12.01%, odds ratio [OR] 1.98, and 31.43% vs 18.00%, OR 1.75, respectively); the antigen combinations B8-DR3, B8-Cw7-DR3, and A1-B8-Cw7-DR3 were significantly more frequent in Graves' patients vs control subjects; in addition, these combinations were present exclusively in patients with persistent disease (B8-DR3 28.95%, OR 7.14, B8-Cw7-DR3 27.63%, OR 11.24, and A1-B8-Cw7-DR3 18.42%, OR 11.29). These data provide evidence that not only susceptibility to Graves' disease, but also persistent activity of the autoimmune process, producing either hyperthyroidism or stable hypothyroidism, is associated with specific HLA antigen phenotypes.

Adolescent↗
PubMed1995

Typical interhemispheric subdural haematomas and falx syndrome: four cases and a review of the literature.

Typical Interhemispheric Subdural Haematomas (ISDHs) are located along the whole interhemispheric fissure. In the four cases of our series, three of which surgically treated, and in the 29 cases reported in literature ISDH has been usually encountered in elderly age (mean age 56) in most of cases following head injury. Anticoagulant therapy was a favouring factor. The source of bleeding was never demonstrated at surgery, nevertheless some authors report a parafalcic bridging-veins laceration due to a brain linear acceleration during trauma, as cause. Clinically, immediate loss of consciousness was usually absent. Focal symptoms arose within 8-48 hours after trauma. In the majority of cases with ISDH, focal symptoms have been characterized by controlateral motor palsy with crural dominance as it has been observed in the "falx syndrome". Facial palsy was absent in all cases but one. Skull fractures were rare. On CT scan ISDH was shown as a spontaneously high density parafalcic area in a flat-convex lenticular shape. In the only case studied with MRI, the site where the ISDH emerged at brain convexity from the interhemispheric fissure, has been clearly localized by means of multiplanarity reconstructions, allowed us a target surgical approach. The majority of patients underwent surgery. The overall mortality rate was 24%: 14% among the 7 cases conservatively treated and 27% among the 26 operated ones. These last patients had a good recovery in 58% and an improvement in 15%. Surgical treatment must be promt as much as possible because of the possible sudden worsening of patient clinical conditions. Craniotomy is the surgical treatment that achieved the best results, nevertheless in our opinion the additional data offered by MRI may repropose the use of target cranial burr holes.

Adult↗
PubMed1994

Airway response to a bronchodilator in healthy parents of infants with bronchiolitis.

In order to assess the role of genetic factors and environmental influences in bronchial responsiveness, we studied the airway response to an inhaled bronchodilator in 66 nonasthmatic parents (age, 30.9 +/- 5.9 years) of infants with bronchiolitis (group 1). It was a placebo-controlled double-blind study. A control group (group 2) of healthy parents of infants who did not have bronchiolitis also were investigated with the test of bronchodilator response. All subjects showed normal expiratory airflow and lung volumes (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and mean forced expiratory flow during the middle half of FVC [FEF25-75%] > 80 percent of predicted) at baseline forced expiratory maneuver. In 16 (24.2 percent) subjects of group 1, there was significant increase in at least one parameter after salbutamol administration, but not after placebo inhalation, with respect to baseline levels. Furthermore, no significant changes in FVC, FEV1, or FEF25-75% values were found in group 2. In conclusion, this study confirms that parents of infants with bronchiolitis have an enhanced airway responsiveness, greater than control parents. Further studies are needed to assess whether one may infer the outcome of infants with bronchiolitis from this characteristic in their parents.

Adult↗
PubMed1994

[Not Available].

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Cardiology↗
PubMed1994

[Brief analytical review of additional possible mechanisms in the pathogenesis of AIDS].

It is generally agreed that HIV itself has the primary role in the initiation and propagation of the pathogenic process of the infection. Nonetheless, a number of important issues concerning the pathogenesis of HIV infection remain unresolved. For example, it remains unclear how CD4+ T cells are lost after HIV infection. The low frequency of infected cells seen even in advanced infection implies that a direct cythopathic effect of HIV on infected CD4+ T cells cannot explain their disappearance. Multiple and diverse mechanisms have been proposed as supplements to the HIV in the destruction of CD4+ cells and the pathogenesis of AIDS. However, it is not yet possible to state confidently which additional mechanism(s) is important. Identification of the nature of this supplemental process has become essential for successful, non-harmful intervention. We propose here a short analytical review of the possible supplemental mechanisms of immunological destruction in AIDS in order to emphasize the complexity of the pathogenesis of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Giant fusiform aneurysm in middle cerebral artery branches: a report of two cases and a review of the literature.

Giant fusiform aneurysm (2.5 cm in length or more) is an unusual pathological entity typically described involving the main trunks of cerebral arteries and, rarely, cerebral artery branches. We are presenting two cases of middle cerebral artery branch giant fusiform aneurysm, one surgically and the other conservatively treated. We were unable to find in the literature reports of similar aneurysms at the same location. Clinical and pathological aspects, radiological findings, and treatment are discussed.

Cerebral Angiography↗
PubMed1993

Pure subdural haematomas of arteriolar origin.

Fifteen consecutive cases of subdural haematomas (SDHs) of arteriolar origin operated on during the last twenty years in the Neurosurgical Clinic of the University of Genoa are reported. These SDHs are rare and form as a result of a rupture of a cortical arteriolar branch typically on the vicinity of the Sylvian fissure. They are always in a pure form and never associated with parenchymal lesions. Their aetiology is spontaneous, as in the 40% of our series, or more frequently related to minor traumas. These SDHs are often encountered in elderly patients generally presenting with severe clinical conditions (in the 60% of our patients GCS on admission was < 8). Prompt surgical treatment is required in all cases before further worsening of their neurological condition, even if CT scanning does not reveal parenchymal lesions. The mortality rate is over 50% and mainly relates to the pre-operative GC score. Clinical features, neuroradiological aspects and treatment are discussed and literature reviewed.

Adult↗
PubMed1993

Reduction of insulin resistance after correction of nonneoplastic ovarian virilization.

A 60-year-old woman with a progressive virilization for about 5 yr developed diabetes mellitus with elevated insulin levels (fasting insulinemia ranging 32.4-45.8 microU/ml). The marked increase of plasma testosterone (total 5.7-8.2 ng/ml; free 11.5 pg/ml) and other endocrine markers clearly indicated the ovarian origin of hyperandrogenism. Pelvic ultrasonography, computerized axial tomography, and direct examination of ovaries during laparotomy, showed no evidence of neoplasia. Microscopic examination and immunocytochemical investigations confirmed the diagnosis of hyperthecosis. After oophorectomy and regression of hyperandrogenism, fasting and postprandial blood glucose concentrations normalized in spite of persistently elevated levels of insulinemia (fasting values ranging 32.0-61.0 microU/ml). The present case suggests that pathological increase of testosterone can interfere with insulin-glucose balance impairing the peripheral sensitivity to insulin.

Blood Glucose↗
PubMed1993

Prognostic significance of the CaMBr1 antigen on breast carcinoma: relevance of the type of recognised glycoconjugate.

An extensive study of the expression of the blood group-related antigen CaMBr1 has been performed by immunohistochemistry, immunoblotting and high performance thin layer chromatography both on frozen and paraffin-embedded (paraffin) samples from normal and neoplastic breast tissues. The glycolipid antigenic fraction (from frozen samples) was preferentially expressed on functioning breast epithelium. In a prospective series of 143 breast cancer cases CaMBr1 expression was associate, on frozen sections, with the transferrin receptor (P = 0.01), the positivity with oestrogen receptor immunochemical assay (P = 0.06), premenopausal status (P = 0.06) and node negativity (P = 0.07). Non-significant correlation with longer disease-free survival (DFS) was observed. In a retrospective series of 862 cases on paraffin sections the glycoproteic antigenic fraction was significantly associated with premenopausal status (P < 0.05) and lobular histotype (P < 0.01), but failed to predict survival, although a trend for longer DFS was observed for positive cases.

Antigens, Neoplasm↗