Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation

Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.     

Ultrasound-guided brachial plexus block in a patient with multiple glomangiomatosis

BACKGROUND AND OBJECTIVES: Glomangiomas are rare, vascular tumors consisting of an afferent artery, arteriovenous canal, neuro-reticular elements, collagen, and efferent veins, and are most often located in the soft tissue of the upper extremities. We describe how the use of ultrasound-guided nerve blockade altered the anesthetic management of a patient with multiple glomangiomatosis undergoing elective forearm surgery. ULTRASOUND FINDINGS: A 32-year-old man was scheduled for excision of painful glomangiomas from the ulnar aspect of his right wrist, with exploration of his ulnar nerve. The anesthetic concerns included (1) morbid obesity, (2) chronic pain syndrome and opioid intolerance, (3) a potentially difficult airway, and (4) obstructive sleep apnea. Ultrasound-guided supraclavicular blockade was the proposed anesthetic of choice. Ultrasound scan of the supraclavicular fossa revealed numerous vascular lesions surrounding the divisions of the brachial plexus. Color Doppler imaging confirmed these pulsatile lesions to be vascular in origin. Even under two-dimensional ultrasound guidance, we believed that the risk of vascular puncture and unintentional intravascular injection of local anesthetic was high, and therefore we abandoned the supraclavicular approach. A successful ultrasound-guided axillary brachial plexus blockade was performed uneventfully. CONCLUSIONS: Although multiple glomangiomatosis is a rare disease, this case illustrates the invaluable contribution that ultrasound has made to modern, regional anesthetic practice, especially for patients with aberrant anatomy in whom traditional nerve-localization techniques could result in serious complications.     

Spontaneous coronary dissection in late pregnancy: a multidisciplinary approach to management

Spontaneous coronary dissection is a rare but potentially life-threatening condition. It often occurs in late pregnancy and may pose significant risks for the patient and the fetus. Its cause remains uncertain, and established guidelines for management have not been developed. In this report, close multidisciplinary collaboration has led to excellent outcomes in this condition.     

Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) of the salivary glands exhibits persistent growth, invasion and metastasis. Chromosome 11q13 amplification is a frequent event associated with tumor progression in a number of carcinomas and is associated with poor prognosis. Two genes within the 11q13 amplicon that are overexpressed as a result of 11q13 amplification are the cell cycle regulatory protein cyclin D1 (CCND1) and cortactin (CTTN), a protein involved cell motility and invasion. To determine the expression and gene status of cyclin D1 and cortactin in ACC, we evaluated 39 ACC cases by immunohistochemistry (IHC) for cyclin D1 and cortactin expression. Amplification of CCND1 and CTTN was determined by fluorescent in situ hybridization (FISH). Cyclin D1 overexpression was present in 90% (35/39) and cortactin expression in 62% (24/39) of evaluated cases, although CCND1 and CTTN levels were elevated in only two cases (5%) as determined by FISH. Our results indicate that chromosome 11q13 amplification is uncommon in ACC, but that cyclin D1 and cortactin are frequently overexpressed and may therefore contribute to the growth and invasive potential of ACC.     

Impact of Varicocelectomy on Gonadal and Erectile Functions in Men with Hypogonadism and Infertility

IntroductionPrevious reports linked varicocele in infertile males with Leydig cell dysfunction and hypogonadism.AimThe aim of this study was to determine the impact of varicocelectomy on serum total testosterone (TT) level and erectile function in men with infertility and clinical varicocele.MethodsThis study included 141 heterosexual infertile men diagnosed to have clinical varicocele. They were divided into two groups: group 1 (103 men), who had microsurgical varicocelectomy, and group 2 (38 patients), who decided to pursue assisted reproduction procedures. All participants completed the International Index of Erectile Function (IIEF)‐5 questionnaire and underwent semen analysis. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and TT were measured both at recruitment time and 6 months later.Main Outcome MeasureChanges in serum TT and IIEF‐5 following varicocelectomy.ResultsIn group 1, the mean TT level increased significantly post‐varicocelectomy (379.1 ± 205.8 to 450.1 ± 170.2 ng/dL, P < 0.0001). No similar change was found in group 2. Out of the 49 patients in group 1 with hypogonadism at baseline assessment (TT < 300 ng/dL), 37 (75.5%) exhibited a postoperative normalization of TT. However, only 3/15 hypogonadal men (20%) in group 2 had normal testosterone levels at the second visit. IIEF‐5 scores improved significantly postoperatively in patients with hypogonadism (17.1 ± 2.6 to 19.7 ± 1.8, P < 0.001). Neither operating vein diameter 3.6 ± 0.57 mm nor testicular size 10.46 ± 3.3 mL correlated with the mean change in TT (71.1 ± 101.2 ng/dL) (r = 0.162, P = 0.183 and r = ?0.077, P = 0.536, respectively).ConclusionsVaricocele is associated with hypogonadism in some infertile patients. Varicocelectomy significantly improves serum testosterone in infertile men, especially those with hypogonadism. This improvement in TT level may be reflected in the IIEF score. Zohdy W, Ghazi S, and Arafa M. Impact of varicocelectomy on gonadal and erectile functions in men with hypogonadism and infertility.     

Management of resistant halo nevi

Background: Halo nevus (HN) is a rare dermatologic disorder characterized by typical whitish rim surrounding an existing melanocytic nevus resembling halo. It is a cosmetic problem that may be linked to vitiligo, and it is advised to remove these nevi in order to avoid development of vitiligo.

Objectives: The aim of the present study is to evaluate the cosmetic outcome after nevus removal and leukoderma dermabrasion with epithelial graft followed by narrow-band ultraviolet B (NB-UVB) phototherapy as management of resistant halo nevi and avoidance of development of vitiligo.

Patients and Methods: Ten patients with persisting halo nevi were selected as candidates in this study. Superficial dermabrasion was carried out using proper diamond fraises on depigmented rim and then punch biopsy probes with suitable size were used to harvest the nevus. Thiersch graft was prepared and applied on the dermabraded depigmented area. After 1 week of the procedure, patients were exposed to NB-UVB twice weekly and were followed up for 3 months.

Results: Repigmentation was noticed in 2 weeks and was nearly fully accomplished in all 10 patients within the 3-month period. No other vitiligo lesions developed during this period in all patients except for one case.

Conclusion: Excision of Sutton’s nevus with combined dermabrasion and Thiersch grafting followed by phototherapy is a good aesthetic maneuver in treating halo nevi and helps in avoiding further vitiligo depigmentation.     

Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes

Inducing an apoptotic response is the goal of most current chemotherapeutic interventions against cancer. However, little is known about the effect of chemotherapeutic agents on the alternative splicing of apoptotic genes. Here, we have tested 20 of the mainstream anticancer drugs for their ability to influence the production of Bcl-x splice isoforms. We find that many drugs shift splicing toward the proapoptotic Bcl-x(S) splice variant in 293 cells. The drugs modulate splicing decisions most likely through signaling events because the splicing switch is not compromised by inhibiting de novo protein synthesis or the activity of caspases. Several drugs also shift Bcl-x splicing in cancer cell lines (MCF-7, HeLa, PC-3, PA-1, and SKOV-3), but the set of active drugs varies between cell lines. We also examined the effect of anticancer agents on the alternative splicing of 95 other human apoptotic genes in different cell lines. Almost every drug can alter a subset of alternative splicing events in each cell line. Although drugs of the same class often influence the alternative splicing of the same units in individual cell lines, these units differ considerably between cell lines, indicating cell line-specific differences in the pathways that control splicing.     

Appendicitis in children treated by pediatric versus general surgeons

BACKGROUND: Pediatric appendicitis is treated by both pediatric and general surgeons. We investigated whether specialty-dependent differences existed in patients' characteristics and outcomes. STUDY DESIGN: A retrospective chart review of 465 consecutive children treated for appendicitis at a university-affiliated children's hospital during a 28-month period was performed. Characteristics and outcomes of patients treated by pediatric surgeons were compared with those treated by general surgeons. Rates of misdiagnosis, postoperative readmission, wound infection, intraabdominal infection, and duration of hospital stay were considered primary outcomes and analyzed by chi-square, Fisher's exact test, or Student's t-test where appropriate. Hospital charges were considered secondary outcomes and analyzed by Wilcoxon rank sum test. RESULTS: Three hundred four children (65%) were treated by pediatric surgeons and 161 (35%) by general surgeons. Pediatric-surgeon patients were younger (8.3 +/- 3.6 versus 13.2 +/- 3.1 years, p < 0.001), and more likely to have gangrenous or perforated appendicitis (54% versus 33%, p < 0.001). There was no significant difference in the normal appendix rate (pediatric surgeon, 4.3% versus general surgeon, 5.6%, p = 0.53). In patients with simple and complicated appendicitis, there were no significant differences between pediatric and general surgeons in readmissions, postoperative complications, or hospital stay. Median hospital charges were not significantly different for complicated appendicitis, but were lower for pediatric-surgeon patients with simple appendicitis (10,735 dollars versus 11,613 dollars, p = 0.005). CONCLUSIONS: Pediatric surgeons treat younger children with more severe appendicitis. There are no specialty-dependent differences in clinical outcomes for simple or complicated appendicitis. Hospital charges are lower for simple appendicitis treated by pediatric surgeons.