Chiari II malformation: MR imaging evaluation

The purpose of this study was to explore the value of high-detail MR imaging in the diagnosis of the Chiari II malformation. Twenty-four patients with known Chiari II malformation as diagnosed by CT scanning were evaluated with cranial MR scans. Two patients also had spine scans. The sagittal-plane images were the most informative, and abnormalities of the telencephalon, diencephalon, mesencephalon, rhomboencephalon, upper spinal cord, and mesencephalon were shown extremely well. We found MR to be an easy and accurate method for demonstrating the abnormalities of the Chiari II malformation, and it is our procedure of choice.     

The differential retrocardiac air-fluid level: a sign of intrathoracic gastric volvulus

A single retrocardiac air-fluid level on a chest radiograph typically implies the presence of a sliding hiatal hernia. A differential retrocardiac fluid level (two air-fluid interfaces at different heights) suggests not a simple sliding hiatal hernia but rather an intrathoracic gastric volvulus. Simultaneous fluid levels above and below the diaphragm are not required to make the diagnosis. We have seen four patients with chronic gastric volvulus confirmed by upper gastrointestinal barium examination. Each case was diagnosable on the basis of the chest radiographs obtained on admission, using the radiographic sign described above. We draw attention to this sign because chronic gastric volvulus has the potential to progress to acute volvulus and gastric ischemia or infarction.     

Double-orifice mitral valve with intact atrioventricular septum: an echocardiographic study with anatomic and functional considerations.

We identified 18 patients with double-orifice mitral valve (DOMV) and intact atrioventricular (AV) septum out of 40,179 echocardiographic studies performed between 1997 and 2002 at Children's Hospital, Denver, CO. In this study we describe (1) the anatomic characteristics of the DOMV in the absence of AV septal defect, (2) the function of the mitral valve by spectral and color Doppler flow mapping, and (3) associated lesions. The topographic location of the orifices in the leaflets suggests possible embryologic mechanisms of DOMV. In this series, DOMV was most commonly associated with left-sided obstructive lesions (in 39% of patients). Spectral and color Doppler interrogation demonstrated a normal flow profile in most cases; only 2 patients had significant mitral regurgitation or stenosis. Therefore, due to the uncertain natural history of this lesion and the potential need for endocarditis prophylaxis, careful imaging of the mitral valve is recommended, particularly in the presence of left-sided obstructive lesions.     

Interferon-gamma knockout fails to confer protection against obliteration in heterotopic murine tracheal allografts.

BACKGROUND: Interferon-gamma, produced by T-helper cells, activates macrophages and increases expression of major histocompatibility complex (MHC) products in acute and chronic rejection. We investigated the role of interferon-gamma in murine heterotopic tracheal allografts. METHODS: Tracheas from BALB/c mice were heterotopically transplanted to BALB/c (12 isografts: 2 weeks [n = 6] and 4 weeks [n = 6], C57BL/6 (12 allografts: 2 weeks [n = 6] and 4 weeks [n = 6]) and C57BL/6 interferon-gamma knockout mice (12 interferon-gamma knockout allografts: 2 weeks [n = 4] and 4 weeks [n = 8]). BALB/c interferon-gamma knockout tracheas were transplanted to C57BL/6 mice (reverse knockout: 4 weeks [n = 6]) and BALB/c interferon-gamma knockout mice (4 weeks [n = 2]). C57BL/6 tracheas were transplanted to Bm12 mice (MHC Class II mismatch allografts: 4 weeks [n = 6]). Conventional histology and immunohistochemistry for CD4, CD8 and CD11b were performed. RESULTS: Minimal (<20%) obliteration was seen at 2 weeks in the allograft groups. No obliteration was seen in the isograft groups. However, all allografts were completely obliterated at 4 weeks. Interferon-gamma knockout allograft combinations displayed severe rejection characterized by intense intra- and extraluminal infiltration by CD4-, CD8- and CD11b-labeled cells. The MHC Class II mismatch allograft group showed normal epithelium and mild sub-epithelial infiltration by CD4+ cells at 4 weeks (CD8-, CD11b-). CONCLUSIONS: Absence of interferon-gamma does not protect the allograft from obliteration. Epithelial destruction by cytotoxic T cells appears to be an important mechanism in the development of obliteration in murine heterotopic tracheal allografts.     

TGF-beta promotes the establishment of renal cell carcinoma bone metastasis.

Bone metastases develop in approximately 30% of patients with RCC, and the mechanisms responsible for this phenomenon are unknown. We found that TGF-beta1 stimulation of RCC bone metastasis cells promotes tumor growth and bone destruction possibly by stimulating paracrine interactions between tumor cells and the bone. INTRODUCTION: Bone metastasis is a frequent complication and causes marked morbidity in patients with renal cell carcinoma (RCC). Surprisingly, the specific mechanisms of RCC interaction with bone have been scarcely studied despite the inability to prevent or effectively treat bone metastasis. Bone is a reservoir for various growth factors including the pleiotropic cytokine TGF-beta1. TGF-beta1 has been shown to have tumor-supportive effects on advanced cancers and evidence suggests its involvement in promoting the development of breast cancer bone metastasis. Here, we studied the potential role of TGF-beta1 in the growth of RCC bone metastasis (RBM). MATERIALS AND METHODS: To inhibit TGF-beta1 signaling, RBM cells stably expressing a dominant-negative (DN) TGF-betaRII cDNA were generated. The in vivo effect of TGF-beta1 on RBM tumor growth and osteolysis was determined by histological and radiographic analysis, respectively, of athymic nude mice after intratibial injection of parental, empty vector, or DN RBM cells. The in vitro effect of TGF-beta1 on RBM cell growth was determined after TGF-beta1 treatment by MTT assay. RESULTS: TGF-beta1 and the TGF-beta receptors I and II (TGF-betaRI/II) were consistently expressed in both RBM tissues and cell lines. Inhibition of TGF-beta1 signaling in RBM cells significantly reduced tumor establishment and osteolysis observed in vivo after injection into the murine tibia, although no effect on tumor establishment was observed after injection of RBM cells subcutaneously or into the renal subcapsule. Treatment of five RBM cell lines with TGF-beta1 in vitro either had no effect (2/5) or resulted in a significant inhibition (3/5) of cell growth, suggesting that TGF-beta1 may promote RBM tumor growth indirectly in vivo. CONCLUSIONS: TGF-beta1 stimulation of RBM cells plays a role in promoting tumor growth and subsequent osteolysis in vivo, likely through the initiation of tumor-promoting paracrine interactions between tumor cells and the bone microenvironment. These data suggest that inhibition of TGF-beta1 signaling may be useful in the treatment of RBM.     

Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy: potentially serious and unappreciated complications of Roux-en-Y gastric bypass.

BACKGROUND: Neither the presence nor prevalence of enteric hyperoxaluria has been recognized after Roux-en-Y gastric bypass (RYGBP). We have noted a high rate of oxalate nephrolithiasis and even 2 patients with oxalate nephropathy in this patient population postoperatively. Our aim was to determine the frequency of the occurrence and effects of enteric hyperoxaluria after RYGBP. METHODS: Retrospective review of all patients at our institution diagnosed with calcium oxalate nephrolithiasis or oxalate nephropathy after standard (n = 14) or distal (n = 9) RYGBP. The mean postoperative follow-up was 55 months. RESULTS: A total of 23 patients (14 men and 9 women; mean age 45 years; mean preoperative body mass index 55 kg/m(2)) developed enteric hyperoxaluria after RYGBP, defined by the presence of oxalate nephropathy (n = 2) or calcium oxalate nephrolithiasis (n = 21) and increased 24-hour excretion of urinary oxalate and/or calcium oxalate supersaturation. Enteric hyperoxaluria was recognized after a mean weight loss of 46 kg at 29 months (range 2-85) after RYGBP. Two patients developed renal failure and required chronic hemodialysis. Of the 21 patients with nephrolithiasis, 14 had no history of nephrolithiasis preoperatively, and 19 of 21 required lithotripsy or other intervention. Of the 23 patients, 20 tested had increased oxalate excretion, and 14 of 15 tested had high urine calcium oxalate supersaturation. CONCLUSION: Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP. Efforts should be made to identify factors that predispose patients to developing hyperoxaluria.     

Integrating disability management into strategic plans: creating healthy organizations.

The integration of disability management into the strategic planning of a corporation ensures a work environment is created that motivates employees to consistently meet customer expectations. Disability management strategies can achieve significant decreases to the human and financial cost of workers' compensation, sick leave or short term disability, and long-term disability. The business case for disability management including effective return to work programs clearly supports program implementation to enhance employee engagement, delivery of corporate priorities, and improvement to the company's bottom line.