A novel DKC1 mutation,severe combined immunodeficiency (T+B-NK- SCID) and bone marrow transplantation in an infant with Hoyeraal-Hreidarsson syndrome

X-linked Hoyeraal-Hreidarsson syndrome (XL-HHS) is the severe infantile variant of X-linked dyskeratosis congenita (XL-DC) and both are due to mutations in the DKC1 gene within Xq28. We report a novel missense mutation in DKC1 exon 3 (T113-->C, Ile38Thr) in a Sardinian infant with XL-HHS in whom the disease was characterized by 'T+B-NK-' severe combined immunodeficiency and bone marrow failure. He underwent sibling bone marrow transplantation using a conditioning regimen (fludarabine, rabbit antithymocyte globulin, low-dose melphalan) selected according to the HHS/DC phenotype. This was associated with low toxicity, prompt engraftment with adequate immune reconstitution and full donor haemopoiesis.     

Relationship between leptin levels and bone mineral density in the elderly

OBJECTIVE: To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly. DESIGN: A cross-sectional study. PATIENTS: A cohort of 92 men and 171 women, with ages ranging from 68 to 75 years, selected as a healthy and normal functioning group, in the city centre of Verona. MEASUREMENTS: Plasma leptin levels were determined in each participant. Body composition was evaluated with dual energy X-ray absorptiometry (DXA). Bone mineral content (BMC) and bone mineral density (BMD) were measured at whole-body, hip and femoral neck level in all subjects. RESULTS: In both men and women a significant relationship between fat mass and whole-body BMC or BMD was found. The strength of this association was consistently reduced after adjustment for plasma leptin. A significant association between circulating leptin levels, whole-body, total hip and femoral neck BMC and BMD was found in both sexes. This association retained the statistical significance after adjustment for fat mass percentage, especially in women. In stepwise multiple linear regression analyses, leptin was shown to be a significant predictor of whole-body, total hip and femoral neck BMC and BMD, independently of age and the percentage of body fat in both sexes. The circulating levels of leptin accounted for a variance in whole-body BMC of 8.9% in men and 18.2% in women, and in whole-body BMD of 10.6% in women. CONCLUSION: Our data show a significant relationship between leptin, bone mineral mass and density in healthy elderly men and women.     

Platelet-derived growth factor C induces liver fibrosis, steatosis, and hepatocellular carcinoma

Members of the platelet-derived growth factor (PDGF) ligand family are known to play important roles in wound healing and fibrotic disease. We show that both transient and stable expression of PDGF-C results in the development of liver fibrosis consisting of the deposition of collagen in a pericellular and perivenular pattern that resembles human alcoholic and nonalcoholic fatty liver disease. Fibrosis in PDGF-C transgenic mice, as demonstrated by staining and hydroxyproline content, is preceded by activation and proliferation of hepatic stellate cells, as shown by collagen, alpha-smooth muscle actin and glial fibrillary acidic protein staining and between 8 and 12 months of age is followed by the development of liver adenomas and hepatocellular carcinomas. The hepatic expression of a number of known profibrotic genes, including type beta1 TGF, PDGF receptors alpha and beta, and tissue inhibitors of matrix metalloproteinases-1 and -2, increased by 4 weeks of age. Increased PDGF receptor alpha and beta protein levels were associated with activation of extracellular regulated kinase-1 and -2 and protein kinase B. At 9 months of age, PDGF-C transgenic mice had enlarged livers associated with increased fibrosis, steatosis, cell dysplasia, and hepatocellular carcinomas. These studies indicate that hepatic expression of PDGF-C induces a number of profibrotic pathways, suggesting that this growth factor may act as an initiator of fibrosis. Moreover, PDGF-C transgenic mice represent a unique model for the study of hepatic fibrosis progressing to tumorigenesis.     

Treatment of renal angiomyolipoma: pooled analysis of individual patient data

Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. The mean ages of groups A and B were 24.6 ± 19.7 (range, 8–52 months) and 31.4 ± 20.6 months (range, 10–59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P < 0.001). The incidence of epididymal anomalies in boys with undescended testis was significantly different according to testis location. Epididymal anomalies were observed in 100 %, 91.4 %, and 39.3 % of cases when the testis was located in the abdomen, inguinal canal, and distal to the external inguinal ring, respectively (P < 0.001). We conclude that epididymal anomalies were more frequent in boys with undescended testis than in boys with hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.     

Laparoscopic management of intra-abdominal infections: Systematic review of the literature

AIM: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections.METHODS: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically.RESULTS: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controlling the source.CONCLUSION: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections.     

Diagnostic decision support systems for atrial fibrillation based on a novel electrocardiogram approach

Background

The electrocardiogram (ECG) is one of the most non-invasive techniques to give support to the atrial fibrillation (AF) diagnosis. Several authors use the temporal difference between two consecutive R waves, a method known as RR interval, to perform the AF diagnosis. However, RR interval-based analysis does not detect distortions on the other ECG waves.

Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists

Objective To investigate how North American thyroidologists assess and treat amiodarone‐induced thyrotoxicosis (AIT) and to compare the results with those of the same questionnaire‐based survey previously carried out among European thyroidologists. Design Members of the American Thyroid Association (ATA) with clinical interests were sent by e‐mail a questionnaire on the diagnosis and management of AIT, 115 responses were received from the United States and Canada, representing about one‐third of ATA members with clinical interests. Results The majority of respondents (91%vs. 68% in Europe, P < 0·05) see < 10 new cases of AIT per year, and AIT seems less frequent than amiodarone‐induced hypothyroidism (AIH) in North America (34% and 66% of amiodarone‐induced thyroid dysfunction, respectively, vs. 75% and 25%, respectively, in Europe, P < 0·001). When AIT is suspected, in North America hormonal assessment is mostly based on serum free T4 (FT4) and TSH measurements, while serum free T3 (FT3) determination is requested less frequently than in Europe; thyroid autoimmunity is included in the initial assessment less than in Europe. Most commonly used additional diagnostic procedures include, as in Europe, thyroid colour‐flow Doppler sonography, and to a lesser extent, thyroid radioactive iodine uptake and scan, but Europeans tend to request multiple tests more than North Americans. Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists (21%vs. 10% in Europe in type 1 AIT, P < 0·05, 34%vs. 20% in type 2 AIT, P < 0·05). In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans, but the former use them as monotherapy in 65%vs. 51% of Europeans (P < 0·05) who more often consider potassium perchlorate as an useful addition (31%vs. 15% of North Americans, P < 0·01). Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0·05) or in association with thionamides (16%vs. 25% in Europe, P = NS). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans. If amiodarone therapy needs to be reinstituted, prophylactic thyroid ablation is advised by 76% in type 1 AIT, while a ‘wait‐and‐see’ strategy is adopted by 61% in type 2 AIT, similar to behaviour of European thyroidologists. Conclusion Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.