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Biomedical subjects

R Rinaldi

Publications and source records attributed to R Rinaldi.

At least 55 records · Page 3Linked to original sources
PubMed1999

ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy.

PURPOSE: Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). DMD is associated with an abnormal electroretinogram (ERG) if the mutation disrupts the translation of retinal dystrophin (Dp260). Our aim was to determine if incomplete ERG abnormalities would be associated with heterozygous carriers of dystrophin gene mutations. METHODS: Ganzfeld ERGs were obtained under scotopic and photopic testing conditions from a family which includes the heterozygous maternal grandmother, the heterozygous mother, and her children, two affected boys and dizygotic twin sibs, an unaffected male and heterozygous female. Southern blot analyses were done to characterise the dystrophin mutation. RESULTS: The dystrophin gene was found to contain a deletion encompassing exon 50. The ERGs in the two affected boys were abnormal, consistent with the DMD ERG phenotype. Serial ERGs of the heterozygous females were abnormal; however, they were less severely affected than the DMD boys. The ERG of the female sib showed a greater abnormality than her mother and maternal grandmother. The unaffected twin had a normal ERG. CONCLUSIONS: The ERG shows abnormalities associated with carrier status in this family with a single exon deletion. A large study of confirmed obligate carriers is planned to clarify further the value of the ERG in detecting female heterozygous carriers of dystrophin gene mutations.

Adult↗
PubMed1999

Quantitative immunoprofiles of breast cancer performed by image analysis.

OBJECTIVE: To determine the biopathologic profiles of breast cancer for greater knowledge of tumor natural history and clinical outcome. STUDY DESIGN: In 99 in situ (ISC) and 2718 infiltrating breast carcinomas (IC), biologic markers (estrogen receptor [ER], progesterone receptor [PR] proliferation index, cerbB-2/NEU, p53, bcl-2 and DNA ploidy) were evaluated with an image analysis system (CAS 200/486). In 105 mixed invasive cancers with size < or = 1 cm, a separate analysis of in situ (ISCm) and invasive component (ICm) was obtained. A clinical study of 836 invasive breast cancers was performed. RESULTS: Different biophenotypes were obtained: among ISCs, cribriform type exhibited biologic behavior similar to that of normal breast tissue (ER+, PR+, proliferation index [PI] low, NEU-, p53-, bcl-2+) the opposite profile was displayed by comedo type, and intermediate phenotypes were observed in noncomedo and lobular types. Comparing ISC and ISCm, PI and p53 expression had the highest levels in ISCm with respect to other groups. NEU overexpression exhibited a decreasing value from ICm to IC. Younger women (< or = 40 years) with IC demonstrated a worse biologic profile (high PI, p53+, ER- and size > 2 cm). In multivariate analysis, PI and NEU in node-negative patients, and NEU, PR and size in node-positive ones emerged as prognostic parameters. CONCLUSION: The results underline the importance of the quantitative biologic profile for defining tumor behavior and patient management.

Adult↗
PubMed1998

Modulation of biomarkers in minimal breast carcinoma: a model for human breast carcinoma progression.

BACKGROUND: The widespread use of diagnostic breast imaging has yielded an increase in the detection of in situ, microinvasive, and small invasive carcinomas and has provided opportunities to study the earliest stages of breast carcinoma development. The authors of this report analyzed the pathobiologic features of 577 minimal breast carcinomas (MBCs), including in situ carcinomas and invasive carcinomas < or =1 cm, according to the definition given by Hartmann in Cancer (1984;53:681-4). METHODS: Estrogen and progesterone receptors (ER and PR), proliferation index (PI), and p53 and neu expression were studied by immunohistochemical technique and measured by quantitative image analysis in 99 pure in situ carcinomas (ISCp); in 105 mixed invasive/in situ carcinomas, with a separate analysis of in situ (ISCm) and invasive (ICm) components; and in 373 invasive carcinomas < or =1 cm (IC). Follow-up data were available for 164 invasive carcinomas. RESULTS: A progressive increase in the levels of hormone steroid receptors, from the lowest in ISCm to the highest in IC, was observed (ER, P< 0.001; PR, P=0.005). Levels of PI and p53 expression were higher in ISCm than in the other categories (PI, P=0.007; p53, P=0.046). Overexpression of neu was greater in ICm than in IC (P=0.013). Younger women (< or =40 years) with invasive carcinoma had worse biologic profiles, with lower ER (P < 0.001) and higher PI (P=0.021), neu (P=0.008), and p53 (P=0.040). It was demonstrated clinically that PI and neu were the biologic markers with the highest predictive prognostic values in univariate analysis (PI for recurrence, P < 0.015; neu for recurrence and overall survival, P < 0.001 and P < 0.007, respectively) and in multivariate analysis (neu for recurrence and overall survival, P < 0.007 and P < 0.017, respectively). CONCLUSIONS: Biologic phenotypes of MBC can be interpreted as reflecting a dimension of neoplastic progression capacity that is independent of tumor size. This study suggests that biologic markers can be integrated with traditional pathologic indicators for accurate staging of patients.

Biomarkers↗
PubMed1998

Cholinergic stimulation and nonadrenergic, noncholinergic relaxation of human colonic circular muscle in idiopathic chronic constipation.

The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P<0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.

Acetylcholine↗
PubMed1998

Functional evaluation of 5-hydroxytryptamine receptor activity in rat resistance vessels.

1. To characterize 5-hydroxytryptamine (5-HT) receptors in rat perfused mesenteric vascular bed (MVB), the effect of 5-HT and related compounds was investigated by functional assay. 2. In quiescent preparations, 5-HT elicited a concentration-dependent conctractile response. After addition of ketanserin, a 5-HT2 receptor antagonist, EC50 values were significantly higher than in controls. 3. In noradrenaline (NA)-precontracted preparations, under continuous infusion of ketanserin, 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced relaxation. Their rank order of relaxant potency and maximum effect were sumatriptan > 5-HT > 5-CT. Methysergide (1 microM) and spiperone (20-100 nM) caused a rightward shift of the relaxation curve to sumatriptan. These data suggest that vasodilatation in rat MVB is mediated by an 'atypical' subtype of 5-HT1-like receptor, which reveals a pharmacological profile similar to that of the 5-HT1D receptor. The involvement of both 5-HT3 and 5-HT4 receptors can be ruled out, since tropisetron (up to 10 microM) was not able to antagonize the relaxant effect by sumatriptan. 4. Under granisetron infusion (3 microM), the contractile response evoked by perivascular nervous stimulation, but not exogenous NA contraction, was significantly reduced (P < 0.001). These data demonstrate the presence of 5-HT3 receptors in peripheral neurones, modulating neurotransmitters release.

Animals↗
PubMed1998

Biological profile of in situ breast cancer investigated by immunohistochemical technique.

In 74 in situ breast cancers an immunohistochemical study for estrogen (ER) and progesterone (PR) receptors, proliferation index (PI), and c-erbB-2, p53, and bcl-2 overexpression was performed. Cases were categorized as ductal carcinoma in situ (DCIS) comedo: 24.3% of cases; DCIS non comedo: 27% of cases; DCIS cribriform: 5.4% of cases; lobular carcinoma in situ (LCIS): 16.3% of cases; mixed carcinoma in situ: 27% of cases. Quantitation of immunohistochemical results was obtained with an image analysis computerized system (CAS 200). The cutoff values used were: 10% of positive area for ER, PR, NEU, and bcl-2; 5% of positive area for p53; 13% of PI for proliferative activity. DCIS cribriform and LCIS displayed a higher positivity for ER (92.6 and 93.8% of cases); DCIS cribriform and DCIS non comedo a higher for PR (89 and 75.3%); DCIS comedo presented the highest values for PI (65.4%), NEU (72.8%), and p53 expression (37.3%). All DCIS cribriform and DCIS non comedo and 99.6% of LCIS expressed bcl-2. The results underscore the importance of biological characterization of breast carcinoma in situ with the aim to define lesions natural history.

Adult↗
PubMed1998

Long-term changes in nodular goiter: a 5-year prospective randomized trial of levothyroxine suppressive therapy for benign cold thyroid nodules.

We studied for 5 yr a homogeneous group of 83 patients randomly assigned to a levothyroxine (L-T4) suppressive therapy or to a control group to evaluate changes in nodule or thyroid size, appearance of new nodules, and correlations with clinical parameters. In the control group, mean nodule volume increased significantly after 5 yr (2.12 +/- 1.46 vs. 1.46 +/- 0.77 mL), whereas in the treatment group it decreased, although not significantly (1.45 +/- 1.17 mL vs. 1.53 +/- 0.61 mL). Baseline nodule volume was not different in the two groups, but a significant difference was observed at 5 yr. After 5 yr, sonograms detected 12 new nodules in the control group (28.5%) and 3 (7.5%) in the treatment group. Nodule shrinkage was more frequent in patients with complete TSH suppression, but no correlation was found with other parameters. A significant increase in thyroid size was observed in the control group. In conclusion, long term TSH suppression induced volume reduction in only a subgroup of thyroid nodules, but effectively prevented the appearance of new lesions and increases in nodule and thyroid volume. As the changes in the natural history of nodular goiter are related to prolonged TSH suppression, which can induce unfavorable side-effects, L-T4 suppressive therapy should be reserved for small nodules in younger patients.

Adult↗
PubMed1998

Detection of a 46,XX,der(3)t(3;4)(p25;p16.1) by using chromosome microdissection.

We performed chromosome microdissection in order to define the "de novo" rearrangement observed in a female patient affected by: frontal microgyria, mild psychomotor retardation, thoracic scoliosis, XIIth rib asymmetry and facial dysmorphisms. Through the use of the micro-FISH we evidenced a deletion of the 3p25pter region and a 4p16.1 duplication. We performed a karyotype-phenotype correlation in our patient and in the ones previously reported in literature which had a 3p25pter deletion or the 4p16 duplication.

Adolescent↗
PubMed1997

Dystonia as an isolated symptom of multiple sclerosis?

Sustained dystonia has seldom been reported during the course of multiple sclerosis (MS) [5-8, 10], and has been described as the first manifestation of the disease in only three cases [1,3]. We describe a patient with a diagnosis of laboratory-supported, defined MS in which sustained dystonia was the only neurological symptom.

Brain↗
PubMed1997

Altered thymic endocrine activity along with impairments of peripheral zinc metabolism and T-lymphocyte populations are associated with myasthenia gravis: a follow-up study.

Thymic endocrine activity was assessed by a bioassay to determine the basal activity of thymulin (TH), a zinc dependent hormone, and its in vitro reactivation in two different age groups of patients with myasthenia gravis (MG). Before thymectomy, basal TH plasma levels were increased in patients over the age of 50 years. Plasma zinc levels were increased in all patients, this increment being very high in old patients. One year after thymectomy both TH and zinc plasma levels decreased. While zinc plasma levels were within the normal ranges for their respective ages, TH levels were lower in young and higher in old patients than in age comparable controls. Young patients with MG showed increased CD3,DR positive peripheral T-cells as well as lymphocytes with the CD16,CD56 phenotype. An increment of CD3 positive cells along with CD4 and CD16,CD56 positive cells were found in older patients. Thymectomy partially affected blood lymphocyte representation only in young patients, since CD3,DR T-cells decreased one year after surgery. No significant variations in T-cell representation were found in old patients after thymectomy. Immunosuppression in thymectomized patients did not significantly affected TH and zinc plasma levels. Very high levels of TH and the presence of additional alterations in T-lymphocyte subsets in old patients suggested that differential age related pathogenetic immunological mechanisms might be associated with the disease.

Adolescent↗
PubMed1997

Treatment of chronic hepatitis C with interferon-alpha by monitoring the response according to viraemia.

In chronic hepatitis C (HCV) infection, treatment with interferon is associated with a rather low rate of sustained response and many treated patients do not achieve significant benefit. Efforts have therefore been made to identify non-responders as early as possible to avoid unjustified costs and side-effects. We treated 106 cases of HCV with an algorithm based on the results of sequential alanine aminotransferase (ALT) and HCV RNA determinations, using an initial dose of 6 MU thrice weekly for 4 months, and modified the subsequent treatment according to the biochemical and virological profile. Thirty-three out of 48 patients (68.7%) who were HCV RNA negative with normal ALT at 4 months after initiation of treatment were sustained responders when treated for an additional 4-month period with a reduced 3 MU dose, while sustained response was achieved in 12.5% of HCV RNA positive patients treated with a higher dosage and for a more prolonged period of time. Our findings indicate that HCV RNA monitoring during interferon therapy may be useful in modifying of the treatment schedule for the individual patient.

Adolescent↗
PubMed1997

Brain and skeletal muscle bioenergetic failure in familial hypobetalipoproteinaemia.

OBJECTIVE: To determine whether a multisystemic bioenergetic deficit is an underlying feature of familial hypobetalipoproteinaemia. METHODS: Brain and skeletal muscle bioenergetics were studied by in vivo phosphorus MR spectroscopy (31P-MRS) in two neurologically affected members (mother and son) and in one asymptomatic member (daughter) of a kindred with familial hypobetalipoproteinaemia. Plasma concentrations of vitamin E and coenzyme Q10 (CoQ10) were also assessed. RESULTS: Brain 31P-MRS disclosed in all patients a reduced phosphocreatine (PCr) concentration whereas the calculated ADP concentration was increased. Brain phosphorylation potential was reduced in the members by about 40%. Skeletal muscle was studied at rest in the three members and during aerobic exercise and recovery in the son and daughter. Only the mother showed an impaired mitochondrial function at rest. Both son and daughter showed an increased end exercise ADP concentration whereas the rates of postexercise recovery of PCr and ADP were slow in the daughter. The rate of inorganic phosphate recovery was reduced in both cases. Plasma concentration of vitamin E and CoQ10 was below the normal range in all members. CONCLUSIONS: Structural changes in mitochondrial membranes and deficit of vitamin E together with reduced availability of CoQ10 can be responsible for the multisystemic bioenergetic deficit. Present findings suggest that CoQ10 supplementation may be important in familial hypobetalipoproteinaemia.

Brain↗
PubMed1997

2q35qter duplication syndrome: phenotypic definition.

Two sibs with multiple congenital anomalies and severe mental retardation were found to have a 2q35qter duplication as a result of a balanced maternal translocation. The clinical features of our two cases are compared with those reported in literature as having either a 2q35qter duplication or a wider duplicated segment without the involvement of any other chromosome deletion or duplication. The typical phenotype is described considering the characteristic clinical features as: hypotonia, hypertelorism, short and beaked nose, flat nasal bridge, thin upper lip, micrognathia, low set and dysmorphic ears, clinodactyly finger V and cryptorchidism.

Abnormalities, Multiple↗