Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

Unexplained hyperferritinemia is a common clinical finding, even in asymptomatic persons. When early onset bilateral cataracts are also present, the hereditary hyperferritinemia-cataract syndrome (HHCS), because of heterozygous point mutation in the L ferritin iron-responsive element (IRE) sequence, can be suspected. We sequenced the L ferritin exon 1 in 52 DNA samples from patients referred to us for molecular diagnosis of HHCS. We identified 24 samples with a point mutation/deletion in the IRE. For the 28 samples in which no IRE mutation was present, we also genotyped HFE mutations and sequenced both H ferritin and ferroportin genes. We found an increased frequency of His63Asp heterozygotes (12 of 28) but no H ferritin mutations. We identified 3 new ferroportin mutations, producing, respectively, Asp157Gly, Gln182His, and Gly323Val amino acid replacements, suggesting that these patients have dominant type 4 hemochromatosis. This study demonstrates that both L ferritin IRE and ferroportin mutations can account for isolated hyperferritinemia. The presence of cataract does not permit the unambiguous identification of patients with HHCS, although the existence of a family history of cataract was only encountered in these patients. This raises the intriguing possibility that lens ferritin accumulation might be a factor contributing to age-related cataract in the general population. Additional causes of isolated hyperferritinemia remain to be identified.     

Pulmonary Artery Access Embolization in Patients with Massive Hemoptysis in Whom Bronchial and/or Nonbronchial Systemic Artery Embolization Is Contraindicated

The objective of this paper is to present an alternative therapeutic approach for the treatment of patients with massive hemoptysis in whom bronchial and/or nonbronchial systemic arterial embolization is not possible. We describe a percutaneous procedure for pulmonary segmental artery embolization. Between May 2000 and July 2006, 27 adult patients with hemoptysis underwent percutaneous treatment at our department; 20 of 27 patients were embolized via bronchial and or nonbronchial systemic arteries and 7 patients were embolized via pulmonary artery. Femoral arterial access for systemic artery catheterization and femoral vein access for pulmonary arterial catheterization were used. Gelfoam particles and coils were used for embolization. In this study, we report on three cases of massive hemoptysis from a systemic arterial source in whom bronchial and/or nonbronchial arteries embolization was not possible. Percutaneous embolization via the pulmonary artery access was successful in all three patients. In conclusion, embolization via pulmonary artery is presented as an alternative approach for the management of hemoptysis in patients in whom bronchial arterial embolization is not possible.     

Living-related liver transplantation and vena cava reconstruction after total hepatectomy including the vena cava for hepatoblastoma.

BACKGROUND: In most cases of total hepatectomy (TH) required for hepatoblastoma (HB), the retrohepatic inferior vena cava (IVC) has to be removed with the native liver for complete tumor excision. Because the liver graft procured by living donation has no IVC, a reconstruction of the recipient IVC is needed. We report our experience with living-related liver transplantation (LRLT) and IVC replacement in such cases. METHODS: Between May 1998 and December 1999, four children underwent TH, including IVC and LRLT with IVC replacement for otherwise irresectable HB after chemotherapy (SIOPEL 2 and 3 protocols). IVC reconstruction used an allogenic iliac vein procured from a cadaveric donor (bank graft) in two cases and an internal jugular vein procured from the donor parent in two cases. Median age and weight at surgery were 17 months (range 10-60) and 9.6 kg (range 8.3-17.9). RESULTS: In the living donors, there were two complications of the procurement: one intra-abdominal biliary collection and one subcutaneous abscess. In all four children, complete excision of the tumor could be achieved without any intra-operative complication. One patient died 5 months after LRLT due to lung metastases. Three patients were alive and well with no evidence of tumor recurrence 13-24 months after surgery. Reconstructed IVC was patent in two patients, and asymptomatic thrombosis occurred 2 years after operation in one patient. CONCLUSION: Total hepatectomy including the retrohepatic IVC is not a technical obstacle to LRLT. Therefore, scheduled surgery, at the best time after chemotherapy, can be considered in all patients with otherwise irresectable HBs.     

Shoulder arthroplasty: evolving techniques and indications

The development of modern shoulder replacement surgery started over half a century ago with the pioneering work done by CS Neer. Several designs for shoulder prostheses are now available, allowing surgeons to select the best design for each situation. When the rotator cuff is intact, unconstrained prostheses produce reliable and reproducible results, with prosthesis survival rates of 97% after 10 years and 84% after 20 years. In patients with three- or four-part fractures of the proximal humerus, the outcome of shoulder arthroplasty depends largely on healing of the greater tuberosity, which is therefore a major treatment objective. Factors crucial to greater tuberosity union include selection of the optimal prosthesis design, flawless fixation of the tuberosities, and appropriate postoperative immobilization. The reverse shoulder prosthesis developed by Grammont has been recognized since 1991 as a valid option for patients with glenohumeral osteoarthritis. Ten-year prosthesis survival rates are 91% overall (including trauma and revisions) and 94% for glenohumeral osteoarthritis with head migration. These good results are generating interest in the reverse shoulder prosthesis as a treatment option in situations where unconstrained prostheses are unsatisfactory (primary glenohumeral osteoarthritis with marked glenoid cavity erosion; comminuted fractures in patients older than 75 years; post-traumatic osteoarthritis with severe tuberosity malunion or nonunion; massive irreparable rotator cuff tears with pseudoparalysis; failed rotator cuff repair; and proximal humerus tumor requiring resection of the rotator cuff insertions).     

Sex differences in diencephalon serotonin transporter availability in major depression.

BACKGROUND: Major depression is more prevalent in women than men. The present study evaluated if previous findings that demonstrated decreased 5-hydroxytryptamine (5-HT) transporter availability in depressed patients would be confirmed in a larger sample and also evaluated sex differences. METHODS: Depressed (n = 32) and healthy subjects (n = 32), including 16 pairs of women and men, participated in an iodine-123-2 beta-carbomethoxy-3beta-(4-iodophenyltropane) ([(123)I]beta-CIT) single photon emission computed tomography (SPECT) and a magnetic resonance imaging (MRI) scan. Participants were administered [(123)I]beta-CIT (225.7 +/- 3.7 MBq) and imaged 23.0 +/- 1.6 hours later. Statistical analyses included analysis of variance and a regression analysis of the main and interactive effects of age, sex, and depression. RESULTS: Overall, depressed patients demonstrated 12% lower diencephalon and no change in striatal or brainstem [(123)I]beta-CIT uptake. Significant age by sex, sex by depression, and age by sex by depression interactions were noted due to 22% lower diencephalon [(123)I]beta-CIT uptake in depressed women compared with less than a 1% decrease in depressed men. CONCLUSIONS: As observed previously, diencephalon 5-HT transporter availability is decreased in depressed patients. However, the decrease appears to be sex-specific and age-dependent. These findings suggest that serotonergic mechanisms mediating depressed mood differ between men and women in an age-dependent manner and may explain why young women respond better to treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants.     

Improved toxicity profile following high-dose postprostatectomy salvage radiation therapy with intensity-modulated radiation therapy

Background

With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy.

Objective

Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting.

Design, setting, and participants

A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo.

Intervention

All patients were treated with SRT with either 3D-CRT (n = 109) or IMRT (n = 176). A total of 205 patients (72%) were treated with doses ≥70 Gy.

Measurements

Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition.

Results and limitations

The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p = 0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p = 0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p = 0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p = 0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up.

Conclusions

Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity.     

E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancer

BACKGROUND: This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. METHODS: Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. RESULTS: The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). CONCLUSIONS: The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis.     

Minimum Alveolar Concentration of Volatile Anesthetics in Rats during Postnatal Maturation

Background: Although neonatal rats have become widely used as experimental laboratory animals, minimum alveolar concentration (MAC) values of volatile anesthetics in rats during postnatal maturation remain unknown.

Methods: We determined MAC values of volatile anesthetics in spontaneously breathing neonatal (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2% steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each group), using the tail-clamp technique. MAC and its 95% confidence intervals were calculated using logistic regression and corrected for body temperature (37[degrees]C).

Results: In adult rats, inspired MAC values corrected at 37[degrees]C were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane, 1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58-1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21-2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72-2.01%); and sevoflurane, 3.28% (3.09-3.47%).     

Reverse total shoulder arthroplasty: a review of results according to etiology

BACKGROUND: Reverse total shoulder arthroplasty provides a surgical alternative to standard total shoulder arthroplasty for the treatment of selected complex shoulder problems. The purpose of the present study was to evaluate the effects of etiology on the results of reverse total shoulder arthroplasty. METHODS: Between May 1995 and June 2003, 240 consecutive reverse total shoulder arthroplasties were performed in 232 patients with an average age of 72.7 years. Patients were grouped according to etiology, and the clinical and radiographic outcomes for each group were measured and compared. RESULTS: One hundred and eighty-six patients with 191 retained reverse total shoulder arthroplasty prostheses were followed for an average of 39.9 months. Overall, the average Constant score improved from 23 points before surgery to 60 points at the time of follow-up and 173 of the 186 patients were satisfied or very satisfied with the result. Although substantial clinical and functional improvement was observed in all etiology groups, patients with primary rotator cuff tear arthropathy, primary osteoarthritis with a rotator cuff tear, and a massive rotator cuff tear had better outcomes, on average, than patients who had posttraumatic arthritis and those managed with revision arthroplasty. Dislocation (fifteen cases) and infection (eight cases) were the most common complications among the 199 shoulders that were followed for two years or were revised prior to the minimum two-year follow-up. Patients who received the reverse prosthesis at the time of a revision arthroplasty had a higher complication rate than did those who received the reverse prosthesis at the time of a primary arthroplasty. CONCLUSIONS: The reverse total shoulder arthroplasty prosthesis can produce good results when used for the treatment of a number of other complex shoulder problems in addition to cuff tear arthropathy. Patients with posttraumatic arthritis and those undergoing revision arthroplasty may have less improvement and higher complication rates in comparison with patients with other etiologies. The advanced age of the patients in the present series and the relatively short duration of follow-up suggest that the prosthesis should continue to be used judiciously.