Alagille syndrome (AGS) is an autosomal dominant disorder with developmental abnormalities affecting the liver, heart, eyes, vertebrae, and craniofacial region. The Jagged-1 (JAG1) gene, which encodes a ligand of Notch, has recently been found mutated in AGS. In this study, mutation analysis of the JAG1 gene performed on 20 Italian AGS patients led to the identification of 15 different JAG1 mutations, including a large deletion of the 20p12 region, six frameshift, three nonsense, three splice-site, and two missense mutations. The two novel missense mutations were clustered in the 5' region, while the remaining mutations were scattered throughout the gene. The spectrum of mutations in Italian patients was similar to that previously reported. We also studied in detail a complex splice site mutation, 3332dupl8bp, which was shown to lead to an abnormal JAG1 mRNA, resulting in a premature stop codon. With the exception of the missense mutations, the majority of the JAG1 mutations are therefore likely to produce truncated proteins. Since the phenotype of the patient with a complete deletion of the JAG1 gene is indistinguishable from that of patients with intragenic mutations, our study further supports the hypothesis that haploinsufficiency is the most common mechanism involved in AGS pathogenesis. Furthermore, our data confirmed the absence of a correlation between the genotype of the JAG1 gene and the AGS phenotype.

Alagille Syndrome↗

PubMed1999

Clinical and neuroradiological follow-up in mucopolysaccharidosis type III (Sanfilippo syndrome).

Mucopolysaccharidosis type III (Sanfilippo syndrome) is an autosomal recessive disorder characterised by progressive nervous system involvement with mental retardation, behavioural problems and seizures. Three patients, of 20 months to 12 years of age, were followed up for 3 years both clinically and by using brain magnetic resonance imaging (MRI). Our results suggest that in MPS III patients MRI findings, including atrophy and abnormal or delayed myelination, may precede the onset of overt neurological symptoms. The increasing neurological morbidity is accompanied by different degrees of progressive atrophic changes, mainly affecting the cerebral cortex and the corpus callosum. However, it appears that, across subjects, the rate of MRI changes is unrelated to the severity of the clinical phenotype. On this basis it could be argued that in MPS III the worsening of the neurological symptoms might not necessarily reflect only the progressive cerebral abnormalities detectable by MRI.

Atrophy↗

PubMed1999

Fatal biphasic brainstem and spinal leptomeningitis with Cryptococcus neoformans in a non-immunocompromised child.

Cryptococcal meningitis is one of the most common life-threatening, invasive fungal infections of the central nervous system in patients with defective T-lymphocyte function. It is, however, unusual in children. We report on a non-immunocompromised 10-y-old boy without evidence of immunological abnormality who developed headache, vomiting, disturbances of consciousness and areflexia. Magnetic resonance imaging of the brain and the spinal cord revealed enlargement of the ventricles and high signal lesions in the leptomeninges at the level of the cerebral peduncles and the cervical and thoracic cord. Cerebrospinal fluid analysis was positive for Cryptococcus neoformans. He was treated with amphotericin B and was symptom-free within 1 wk. Despite an extended course of therapy his symptoms suddenly relapsed and he succumbed to the medical complications of cardiac and respiratory failure. Central nervous system appearances at postmortem were those of cryptococcal leptomeningitis.

Arachnoid↗

PubMed1999

The prevalence of coeliac disease in infertility.

An increased incidence of reproductive problems, including infertility, miscarriage, low birth weight newborns, and shorter duration of breast-feeding, are known to exist in women with coeliac disease; some of these conditions are improved by a gluten-free diet. We have tried to ascertain the prevalence of coeliac disease in 99 couples who were being evaluated for infertility, compared with the known prevalence of silent disease in the population of Northern Sardinia, in which it is endemic. Of all women, four tested positive for at least two out of three markers: immunoglobulin A (IgA) antigliadin, immunoglobulin (IgG) antigliadin, and anti-endomysium antibodies, and underwent a jejunal biopsy; three had histological evidence of coeliac disease. One male partner was positive for two markers, and had a diagnostic jejunal biopsy. The prevalence of coeliac disease in infertile women seems higher (three out of 99, 3. 03%) in the study group than in the general population (17 out of 1607, 1.06%), and particularly in the subgroup with unexplained infertility (two out of 25, 8%, P < 0.03). Screening for coeliac disease should be part of the diagnostic work-up of infertile women, particularly when no apparent cause can be ascertained after standard evaluation.

Adult↗

PubMed1998

Endoscopic saphenous vein harvesting versus 'open' technique. A prospective study.

OBJECTIVE: Preparation of the great saphenous vein for coronary artery bypass grafts is usually performed through one or many cutaneous incisions. A technique of endoscopic harvesting is now available. An aim of the study was to compare both methods, prospectively. METHODS: Sixty coronary artery bypass grafting patients were randomly assigned to two groups according to saphenous vein harvesting technique: 30 patients to group 1 -- open harvesting technique (OHT) and 30 patients to group 2 -- endoscopic harvesting technique (EHT). The results were assessed on the basis of (1) clinical outcome (hematomas, inflammations), (2) length of the cutaneous incisions compared to length of the segment of vein harvested, (3) time of harvesting, (4) postoperative pain. RESULTS: Both groups were comparable in terms of: age, sex, diabetes, peripheral artery disease, site of harvesting, number of anastomoses, and length of the vein harvested. Both the length of the cutaneous incisions and the postoperative pain were decreased in the EHT group. Harvesting time was increased in the OHT group. CONCLUSIONS: Endoscopic saphenous vein harvesting allows improved aesthetic aspect, less postoperative discomfort, with an increased time in harvesting in the beginning.

Aged↗

PubMed1998

Genome search in celiac disease.

Celiac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. In addition to the HLA loci, our study suggests that a risk factor in 5qter is involved in both forms of CD (symptomatic and silent). Furthermore, a factor on 11qter possibly differentiates the two forms. In contrast, none of the regions recently published was confirmed by the present screening.

Celiac Disease↗

PubMed1998

Thromboembolic events in beta thalassemia major: an Italian multicenter study.

Thromboembolic (TE) events have been frequently reported in beta-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.

Adolescent↗

PubMed1998

Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement.

Explore the source record for details and available documents.

Cerebral Veins↗

PubMed1998

[Significance of electrocardiographic projection of ST-segment depression during exercise test in the prediction of the location of regional myocardial ischemia].

There is still some controversy whether ST segment depression during exercise testing might predict the location of myocardial ischemia. From a population of 1196 patients who underwent myocardial 99mTc-tetrofosmin exercise SPECT scintigraphy, 22 consecutive patients (20 males and 2 females, mean age 54 +/- 10 years) with no previous myocardial infarction, positive exercise testing (> or = 1 mm ST segment depression) performed in pharmacologic wash-out and angiographically documented isolated single vessel coronary artery disease (> or = 70% diameter stenosis in a main coronary artery) were selected. None of the patients showed > or = 1 mm ST segment depression exclusively in inferior leads (II-III-aVF). Eight patients (36%) showed > or = 1 mm ST segment depression exclusively in precordial leads (Group 1). The remaining 14 patients (64%) showed > or = 1 mm ST segment depression in both inferior and precordial leads (Group 2). No differences between groups were observed regarding peak exercise test parameters such as heart rate (124 +/- 28 vs 135 +/- 21 b/min, NS), rate-pressure product (22592 +/- 5323 vs 23118 +/- 4197 mmHg x b/min, NS) and exercise time (14.5 +/- 3.9 vs 15.1 +/- 2.9 min, NS) and the number of stress-induced reversible and partially reversible defects (3.3 +/- 3.4 vs 4.6 +/- 2.8, NS). All reversible and partially reversible defects were seen in the related coronary artery stenosis region. Among Group 1, 5 patient (62.5%) showed a > or = 70% stenosis of left descending coronary artery, 1 patient (12.5%) of left circumflex and 2 patients (25%) of right coronary artery. Similarly, among Group 2, 9 patients (64.3%) showed a significant stenosis of left descending coronary artery, 1 patient (7.1%) of left circumflex and 4 patients (28.6%) of right coronary artery. Thus, we were not able to show a relation between exercise ST segment depression and the location of myocardial ischemia as assessed by myocardial 99mTc-tetrofosmin SPECT scintigraphy in a population of patients selected on the basis of single coronary artery disease.

Adult↗

PubMed1997

Antibody pattern in childhood celiac disease.

BACKGROUND: We carried out a study of the antibody pattern in 50 celiac children [34 females (F) and 16 males (M); F/M, 2.1], ages 7 months-15 years, compared with that in 25 control subjects (13 females and 12 males) of the same age. METHODS: IgA and IgG antigliadin antibodies (AGA) were determined with an enzyme-linked immunosorbent assay technique. IgA anti-R1-reticulin antibodies (ARA) and IgA antiendomysium antibodies (EmA) were determined with the fluorescein isothiocyanate-conjugate-labeled anti-human immunoglobulin technique. To compare sensitivity and specificity, EmA were identified using monkey esophagus and human umbilical cord as substrates. RESULTS: While AGA (IgA and IgG) showed a high sensitivity but a low specificity, ARA showed a high specificity but a low sensitivity. Data on EmA showed a high sensitivity and specificity with both tissue sections, with monkey esophagus being more sensitive (96%) and umbilical cord more specific (100%). CONCLUSIONS: Our results confirm the importance of celiac disease-related antibodies in identifying celiac children. Moreover, the easy availability of human umbilical cord indicates that it would be proper to use this tissue as substrate, instead of monkey esophagus, for EmA search in the future.

Adolescent↗

PubMed1997

Effect of alpha-interferon on natural killer cell activity and lymphocyte subsets in thalassemia patients with chronic hepatitis C.

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.

Adolescent↗

PubMed1997

Tuberculosis of the ankle in childhood: clinical, roentgenographic and computed tomography findings.

We report on three Italian children who presented with unilateral ankle tuberculosis (TB) consecutively during a short time period and in the same geographical area. A 6-year-old-girl with a family history of TB had limited mobility of the right leg at age 9 months; Mantoux test and radiographs at that age yielded normal findings. When severe right tibiotarsal swelling, reddening, pain and restriction of motion became apparent at age 4.6 years, the typical lesions of TB were evident on radiographs and computed tomographic (CT) scans. Mantoux test and synovial biopsy confirmed TB. A three-drug regimen of treatment proved useless: articular cartilage destruction and diffuse osteosclerosis ensued. Only a four-drug prolonged regimen of treatment proved to be somewhat effective. A 5-year-old girl had a 6-month history of painless swelling and limited mobility of the ankle; radiographs and CT showed osteopenia with marginal erosion of cartilages. A 14-month-old boy presented with a 2-week history of painless swelling ankle. Radiographs showed decreased bone density of talocalcanear bones. Mantoux test and synovial biopsy confirmed TB in both patients; treatment with a three-drug regimen greatly reduced symptoms. A careful suspicion of the diagnosis of tuberculosis is paramount in children with chronic or subacute monoarticular arthritis, even in absence of a positive tuberculin test or abnormalities on chest radiograph. When negative early on, the tuberculin test should be repeated after 6 weeks of arthritis, and a needle biopsy of the synovium is required in those children with monoarticular arthritis and a positive tuberculin test. Careful therapy is necessary to avoid sequelae that may lead to severe osteoarticular damage.

Ankle Joint↗

PubMed1997

[Surgery of the ascending aorta: the 1984-1995 experience of the cardiac surgery teaching unit in the University of Milan. Multivariate analysis of its risk factors for hospital mortality and reduced long-term survival].

Between 1984 and 1995, 183 patients underwent an ascending aorta procedure at our institution. Their mean age was 60 +/- 12.3 years; 116 (63.4%) patients were male, 35 (19.1%) had a history of congestive heart failure, 72 (39.3%) presented acute type A dissection, 23 (12.6%) were redos and 63 (34.4%) were operated on an emergency basis. In-hospital mortality was 10% (12/120) in elective procedures and 36.5% (23/63) in emergency operations (p < 0.0001). Multivariate stepwise logistic regression analysis identified cardiopulmonary by-pass time, emergency operation, arch replacement and the need for femoral vein cannulation at surgery as independent predictors of in-hospital death. Mean follow-up time was 54 +/- 30 months (median 50 months), with a Kaplan-Meier survival of 69 +/- 4% and of 60 +/- 5% at 5 and 7 years, respectively. Cox regression analysis identified arch replacement, perioperative myocardial infarction, preoperative NYHA class, acute type A aortic dissection, the need for femoral vein cannulation at intervention and redo operations as independent predictors of reduced survival at follow-up. When this kind of analysis was performed on hospital survivors only, postoperative tracheostomy, reexploration for bleeding, and the occurrence of postoperative ventricular arrhythmias emerged as risk factors. In conclusion, multiple factors affect both early and long-term outcome following ascending aorta surgery. Preoperative clinical status of patients, priority of surgery and aortic dissection are the main determinants of the short-term results. Otherwise, in hospital survivors, the main determinant for long-term outcome seems to be the immediate postoperative course.

Aged↗

PubMed1996

Acute palsy of the recurrent laryngeal nerve complicating Epstein-Barr virus infection.

We report an 11-year-old boy with active Epstein-Barr virus (EBV) infection who developed acute aphonia and had signs and symptoms of recurrent laryngeal nerve palsy. The association of isolated recurrent laryngeal nerve palsy and EBV infection has not previously been reported. This case report expands the spectrum of neurologic complications of EBV infection, and suggests that infectious mononucleosis should be considered in the differential diagnosis of acute aphonia in children.

Antibodies, Viral↗