High intrafamilial variability in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy: a case study.

INTRODUCTION: Autoimmune polyendocrinopathy- candidiasis-ectodermal-dystrophy syndrome (APECED) is a monogenic disease whose phenotype may reveal wide heterogeneity. The reasons of this variability still remain obscure. PATIENTS AND METHODS: Two APECED siblings with identical genotype and extremely different phenotype were compared with regard to exposure to infectious triggers, autoantibodies' profile, mechanisms of peripheral tolerance, and human leukocyte antigen (HLA) haplotype. The following infectious markers were evaluated: rubella, Epstein Barr virus, cytomegalovirus, toxoplasma, varicella zoster virus, parvovirus B19, herpes simplex virus, and parainfluenza virus. APECED-related autoantibodies were detected by indirect immunofluorescence or complement fixation or enzyme- linked immunosorbent assay or radioimmunoassay. Resistance to Fas-induced apoptosis was evaluated on peripheral blood mononuclear cells (PBMC) activated with phytohemoagglutinin, the number of TCD4+CD25+ regulatory cells (Treg) was evaluated through flow-cytometry and natural killer (NK) activity through Wallac method. Perforin (PRF1) was amplified by PCR and sequenced. RESULTS: No difference was observed between the siblings in common infectious triggers, extent of Fas-induced apoptosis, NK-cell activity and PRF1 sequence, the number of Tregs and HLA haplotypes. CONCLUSION: Although APECED is a monogenic disease, its expressivity may be extremely different even in the same family. This variability cannot be explained by common triggering infectious agents or functional alterations of mechanisms governing peripheral tolerance.

In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by alterations of the A-T mutated (ATM) gene. Although A-T is a non-curable disease, we, previously, documented a clear improvement of cerebellar functions during a short-term betamethasone trial. The aim of this study was to define the underlying biochemical mechanism. METHODS: In six A-T patients receiving a short-term steroid therapy, intracellular glutathione (GSH) levels were evaluated with a colorimetric assay. The lipid peroxidation level and reactive oxygen species (ROS) production were evaluated using commercial assays. All the parameters were compared with the improvement of cerebellar functions expressed as delta (Delta) of the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS: We observed an inverse correlation between Delta SARA and the severity of cerebellar atrophy and between the latter and basal GSH values. Four of the five patients with the highest Delta SARA also had the highest GSH values. Moreover, even though basal ROS values were comparable in patients and controls, in the only patient studied at different time-points of therapy, a remarkable reduction in ROS levels was documented. CONCLUSION: We suggest that antioxidative mechanisms play a role in favouring the improvement of cerebellar functions observed in A-T patients receiving a short-term betamethasone trial.

Longitudinal study on thyroid function in patients with thalassemia major.

UNLABELLED: Primary hypothyroidism is one of the most frequent complications observed in patients suffering from thalassemia. We investigated thyroid function in a group of patients attending the Pediatric Department of Cardarelli Hospital in order to determine in how many patients thyroid function worsened during a 12 year-period of follow up. PATIENTS AND MEASUREMENTS: Fifty patients with beta-thalassemia major (27 females and 23 males), mean age 25.7+/-1.4 years, were re-evaluated according to the criteria of Faglia et al. Thyroid dysfunction was defined as follows: overt hypothyroidism (low FT4 and increased TSH levels >10 microU/ml); compensated hypothyroidism (normal FT4, TSH 5-10 microU/ml, and abnormal TRH test); subclinical hypothyroidism (normal FT4, basal TSH 0-5 microU/ml, abnormal TRH test). Correlation with hematological, biochemical and growth parameters was evaluated. RESULTS: Ten out of 50 patients evaluated in a previous study had moved to other centers, and four patients had died from cardiac problems. Thus, 36 patients completed a 12 year-period of follow-up. In 25% of the patients the degree of thyroid dysfunction worsened with different degrees of severity. The prevalence of overt hypothyroidism had risen to 13.9% from 8.4%. No cases of secondary hypothyroidism were observed, and anti-thyroglobulin and anti-thyroperoxidase (TPO) antibody titers were negative in all patients. Five (28%) out of 17 patients with normal thyroid function previously (one female, four male) showed an exaggerated TSH response to a TRH test, with normal serum levels of FT4, and they were classified as having subclinical hypothyroidism; while another patient died of cardiac complications. Four out of twelve patients with previous subclinical hypothyroidism showed worsening with a different degree of severity: two females changed to compensated hypothyroidism, and two males to overt hypothyroidism. Furthermore, two out of six patients with compensated hypothyroidism and one out of four patients with overt hypothyroidism died of cardiac failure. In all patients there was no correlation between serum ferritin levels, blood transfusion, pretransfusion Hb levels and worsening of thyroid function. Echographic data showed features of dishomogeneity of the parenchyma with different degrees of severity in accordance with the criteria of Sostre and Reyes. The highest score was observed in all patients with overt and compensated hypothyroidism. CONCLUSIONS: A slow worsening of thyroid function was observed in 25% of the studied patients and only two of them developed overt hypothyroidism. The echographic pattern seems to be strongly predictive of thyroid dysfunction.

[Liver rupture in HELLP syndrome. Report of a case]. / Rottura epatica in corso di HELLP sindrome. Descrizione di un caso.

Liver rupture and hemorrhage, are the most unusual and serious complications of HELLP syndrome (hemolysis--elevated liver enzymes--low platelet count). The management should be aggressive by treating coagulopathy and favouring a prompt delivery. Liver rupture remains a surgical emergency with control of bleeding based on trauma surgery. The aggressive approach to the management of these patients led to a remarkable decrease of mortality rates.

[Traumatic liver injuries: advances in diagnostic and therapeutic methods]. / Lesioni traumatiche del fegato: evoluzione delle strategie diagnostico-terapeutiche.

One hundred five patients affected by traumatic rupture of the liver were admitted in the Emergency Surgical Unit at Ospedale "A. Cardarelli" in Napoli over a period of five years. In 40 patients a conservative treatment was applied, monitoring red blood count, and haemoglobin values as well as abdominal ultrasound and CT scans. The remaining 65 patients underwent surgery for liver trauma. Twelve out of 65 patients presented with an hepatic injury alone whereas in 53 liver injury was associated with other lesions, as splenic rupture, kidney hematoma, bone fracture, chest trauma, diaphragmatic or cranial injury. Eleven out of 65 patients underwent postoperative complications such as bile collection (nine) and biliary fistula (two); however, none of these complicated patients died or underwent further surgery. On the basis of their data the Authors conclude that a careful preoperative assessment and the monitoring of haemodynamic pattern are advisable in patients with liver trauma, allowing the choice of a conservative treatment whenever possible. In the patients undergoing surgical treatment, a more conservative approach should be advocated, with a wider use of intraparenchymal haemostasis and packing, both to improve the haemodynamic status and to refer the patient to specialized units.

Antibiotic prophylaxis for biliary tract surgery: selection of patient and agent.

One hundred and three patients undergoing biliary surgery have been entered in a randomized prospective trial for antibiotic prophylaxis. Fifty six received piperacillin (2 gr) and 47 tobramycin (100 mg). Cultures were taken from bile at operation and a clinical and microbiological assessment for infection was carried out postoperatively. Overall infection rate was significantly lower in the piperacillin group (P less than 0.05). The positive bile culture and wound infection rates were also lower in the piperacillin group, though this did not reach statistical significance. Anaerobic bacteria (three patients) and Streptococcus faecalis (one patient) were isolated in the tobramycin group. Overall postoperative infection rate was similar in patients with risk factors for infection and in those without. In conclusion, piperacillin did not significantly improve bile and wound infection rates compared to tobramycin. However piperacillin showed a more appropriate spectrum of activity. Antibiotic prophylaxis is suggested for all patients undergoing biliary surgery.