Extracellular truncations of h beta c, the common signaling subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5, lead to ligand-independent activation

The hypothesis that extracellular truncation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony- stimulating factor, and IL-5 (h beta c) can lead to ligand-independent activation was tested by infecting factor-dependent hematopoietic cell lines with retroviruses encoding truncated forms of h beta c. A truncation, resembling that in v-Mpl, and retaining 45 h beta c-derived extracellular residues, led to constitutive activation in the murine myeloid cell line, FDC-P1. However, infection of cells with retrovirus encoding a more severely truncated receptor, retaining only 7 h beta c- derived extracellular residues, did not confer factor independence on these cells. These experiments show that truncation activates the receptor and define a 37-amino acid segment of h beta c (H395-A431) which contains two motifs conserved throughout the cytokine receptor superfamily (consensus Y/H XX R/Q VR and WSXWS), as essential for factor-independent signaling. The mechanism of activation was also investigated in less severe truncations. A receptor that retains the entire membrane-proximal domain (domain 4) also conferred factor independent growth on FDC-P1 cells; however, a retrovirus encoding a truncated form of h beta c having two intact membrane proximal domains did not have this ability, suggesting that domain 3 may have an inhibitory role in h beta c. The ability of these receptors to confer factor independence was cell specific as demonstrated by their inability to confer factor-independent growth when introduced into the murine IL-3-dependent pro-B cell line BaF-B03. These results are consistent with a model in which activation requires unmasking of an interactive receptor surface in domain 4 and association with a myeloid- specific receptor or accessory component. We suggest that in the absence of ligand intramolecular interactions prevent inappropriate signaling.     

Effect of Intrathecal Baclofen Concentration on Spasticity Control: Case Series

Background/Objective: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.     

Robot-Assisted Transaxillary Thyroid Surgery in the United States: Is it Comparable to Open Thyroid Lobectomy?

Background  

The purpose of this study was to compare the outcome of robot-assisted transaxillary thyroid surgery (RATS) to the standard open technique for thyroid lobectomy in the U.S. population.     

Breast Surgery Outcomes as Quality Measures According to the NSQIP Database

Background

The National Surgical Quality Improvement Program (NSQIP) is a risk-adjusted database designed to benchmark quality initiatives. NSQIP captures uniform morbidity variables for all operations and calculates expected morbidity probabilities. Given the frequent need for reoperation following breast-conserving surgery (BCS) and mastectomy, we hypothesized that NSQIP may inaccurately reflect surgical morbidity after breast cancer operations.

Methods

Using the 2008 NSQIP database, we identified 24,447 breast surgery patients. We calculated the observed versus expected (O/E) morbidity ratios, compared them to other general surgery procedures, and analyzed the O/E morbidity ratios among benign and malignant breast diagnoses.

Results

The NSQIP database shows that breast surgery has an O/E morbidity ratio of 3.11, which is higher than other general surgery procedures. Additionally, breast operations for malignancy have higher O/E morbidity ratios (3.22) than those performed for benign disease (2.59). Analysis of malignant patients by CPT code revealed that BCS patients had an O/E morbidity ratio of 7.75 and attributed 89?% of morbidity to reoperation, whereas mastectomy patients had an O/E morbidity ratio of only 1.7. Elimination of the reoperation variable from morbidity calculations in breast surgery reduces the O/E morbidity ratio to less than expected in all breast procedures.

Discussion

Breast surgery has a higher O/E morbidity ratio than other general surgery procedures. Reoperations are expected in BCS for positive margins and in mastectomy for completion ALND. Breast surgeons should advocate for benchmarking by surgical site-specific metrics, because current NSQIP criteria may negatively affect the quality assessment of high-volume breast centers.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

高压氧综合治疗糖尿病足的临床疗效观察

糖尿病足(diabetic foot,DF)是常见的糖尿病慢性合并症之一,也是导致糖尿病人截肢致残的主要原因.近年来,糖尿病患病率逐年增高,使糖尿病足的患病率也呈逐年上升的趋势.     

Unexpected findings at diagnostic laparoscopy: caecal incarceration with concurrent appendicitis in a patient with bilateral broad ligament defects

Internal herniations through broad ligament defects are very rare. We present the first report of the triad of broad ligament defect, internal herniation of the caecum and appendicitis. A 36-year-old woman with phocomelia presented with right iliac fossa pain and vomiting. The patient had no previous history of trauma or surgery. Abdominal ultrasound showed a small amount of free fluid. At laparoscopy, bilateral broad ligament defects were found, with herniation of the caecum and an inflamed appendix through the right-sided defect. A laparoscopic salpingo-oophorectomy was required for reduction of the herniated bowel, and an appendicectomy was performed. Broad ligament defects may be congenital or acquired. In this case, in light of the limb abnormality and absence of previous surgery, a congenital aetiology is more likely. Ultrasound scan is not reliable and, although computed tomography may be of help, a diagnostic laparoscopy is the best investigation.