Unplanned splenectomy during oesophagectomy does not affect survival.

OBJECTIVE: There are limited and conflicting data available concerning the incidence of inadvertent splenectomy and its impact on the outcome in patients who have undergone oesophagectomy. The aim of this study is to identify the factors associated with a likelihood of inadvertent splenectomy and its influence on early and long-term outcome in patients having oesophagectomy for oesophageal carcinoma. METHODS: A consecutive series of 738 oesophagectomies performed between 1991 and 2004 was analysed. In our practice, the spleen was removed only if damaged intraoperatively. Routine chemo- and immunoprophylaxis would subsequently be used. Multivariate analysis with logistic and Cox models determined significant variables. RESULTS: Of the 738 oesophagectomies, 48 (6.5%) had splenectomy. Neoadjuvant chemotherapy was administered to a minority of patients; none subsequently had splenectomy. There were significant differences between types of operation (Ivor-Lewis 18 (9.0%), left thoracolaparotomy 14 (9.9%) and left thoracophrenotomy 15 (3.9%), p=0.01). Splenectomy was more common with advanced N stage disease (OR=0.44 [0.20-0.95]; p=0.04). Splenectomy resulted in more blood transfusions (median, 2 units vs 0 units; p=0.03) more anastomotic leaks (7 [14.6%] vs 42 [6.1%]; p=0.02) but not an increase in pulmonary complications (p=0.64) or in-hospital mortality (1 [4.6%] vs 37 [5.4%]; p=0.30). Splenectomy did not significantly affect median survival (551 [332-770] days vs 627 [554-700] days; p=0.63). CONCLUSION: Although inadvertent splenectomy increased the morbidity of oesophagectomy, it did not impair survival. Type of operation and advanced N stage are important risks for splenectomy. Though best avoided, most of the consequences of splenectomy can be managed. An unexpected relationship between splenectomy and anastomotic leaks needs further investigation.     

Right ventricle-to-pulmonary artery shunt versus modified Blalock-Taussig shunt in the Norwood procedure for hypoplastic left heart syndrome - influence on early and late haemodynamic status.

OBJECTIVE: The aim of this study was to assess changes in early and late haemodynamic status after the Norwood procedure (NP), caused by the implementation of right ventricle-to-pulmonary artery shunt (RV-PA). METHODS: A consecutive series of 68 children with hypoplastic left heart syndrome underwent NP: Group 1 (n=31) with the application of a modified Blalock-Taussig shunt and Group 2 (n=37) with RV-PA. Haemodynamic data from the early postoperative period (72 h after the operation) and cardiac catheterisation data, as well as blood tests before the hemi-Fontan procedure (HF) were analysed. Univariate (chi(2) test, Mann-Whitney's and Student's t-tests) and multiple regression analysis were carried out. RESULTS: In Group 1, circulatory collapse requiring resuscitation occurred in 15 (48.4%) children, within 72 h after the procedure. The resuscitation was unsuccessful in nine (29%) cases. The operative mortality (30 days) was 35%. In Group 2, two (5%) children died within the early and two (5%) within the late postoperative period. The postoperative course in the remaining children from Group 2 was uneventful. In Group 2 there was a significantly higher mean diastolic pressure after NP (P<0.05). The arterial pulse pressure after NP was significantly lower in Group 2 (P<0.05). Before HF, the application of RV-PA was associated with a lower Qp:Qs ratio (P=0.020), lower aortic pulse pressure (P=0.004) and lower aortic oxygen saturation (P=0.039). CONCLUSIONS: A stable haemodynamic status due to independent coronary perfusion, higher diastolic and lower pulse pressure is the most advantageous effect of RV-PA, resulting in a lower mortality and morbidity after NP. A lower Qp:Qs ratio eliminates the danger of the ventricular volume overload and ensures good conditions for the development of the pulmonary circulation before HF.     

RANK signaling is not required for TNFalpha-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis.

To address the controversy of whether TNFalpha can compensate for RANKL in osteoclastogenesis in vivo, we used a TNFalpha-induced animal model of inflammatory arthritis and blocked RANKL/RANK signaling. TNFalpha increased osteoclast precursors available for RANK-dependent osteoclastogenesis. RANK signaling is not required for the TNFalpha-stimulated increase in CD11b(hi) osteoclast precursors but is essential for mature osteoclast formation. INTRODUCTION: Although critical roles of TNFalpha in inflammatory arthritis and RANKL in bone resorption have been firmly established, a central controversy remains about the extent to which TNFalpha can compensate for RANKL during osteoclastogenesis and the stage at which RANK signaling is required for osteoclastogenesis. Here, we used the human TNFalpha transgenic mouse model (TNF-Tg) of erosive arthritis to determine if there are both RANK-dependent and -independent stages of osteoclastogenesis in TNFalpha-induced erosive arthritis. MATERIALS AND METHODS: Osteoclastogenesis and osteoclast precursor (OCP) frequency were analyzed using histology, fluorescence-activated cell sorting (FACS), and cell culture from (1) TNF-Tg mice treated with the RANKL antagonist, RANK:Fc, or (2) TNF-Tg X RANK -/- mice generated by crossing TNF-Tg mice with RANK-/- mice. RESULTS: Treatment of TNF-Tg mice, which have increased OCPs in their spleens, with RANK:Fc dramatically reduced osteoclast numbers on the surface of their arthritic joints and within their bones, but did not decrease CD11b(hi) OCP numbers in their spleens. Long-term RANK:Fc administration alleviated joint erosion. Furthermore, TNF-Tg x RANK -/- mice had severe osteopetrosis, no osteoclasts, and no joint erosion, but increased CD11b(hi) precursor numbers that failed to form mature osteoclasts in vitro. CONCLUSION: RANK signaling is essential for mature osteoclast formation in TNFalpha-mediated inflammatory arthritis but not for the TNFalpha-induced increase in CD11b(hi) OCP that subsequently can differentiate into osteoclasts in inflamed joints.     

Matrix Metalloproteinases

Drugs & Aging - Matrix metalloproteinases (MMPs), or matrixins, are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. Normally,...     

Gaudier patients with oculomotor abnormalities do not have a unique genotype

Sixteen non-Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro-ophthalmologic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis.     

Prediction of Remission of Acute Posttraumatic Stress Disorder in Motor Vehicle Accident Victims

One hundred forty five individuals who sought medical attention as a result of a motor vehicle accident (MVA), and who were initially assessed 1 to 4 months post-MVA, were followed up prospectively for 6 months to determine how many of the 55 with posttraumatic stress disorder (PTSD) and the 43 with sub-syndromal PTSD would remit and what variables would predict remission. Thirty (55%) of those with initial PTSD had remitted at least in part by 6 months while 67% of those with sub-syndromal PTSD had remitted (and 5% had worsened). Four variables, including severity of initial symptoms, degree of initial physical injury, relative degree of physical recovery by 4 months and whether a close family member suffered a trauma during the follow-up interval, combined to classify 6-month clinical status of 84% of those with initial PTSD secondary to MVAs.     

Coronary artery and saphenous vein graft remodeling: A review of histologic findings after various interventional procedures—part V

Catheter balloon angioplasty is a well accepted form of nonsurgical treatment of acutely and chronically obstructed coronary artery vessels. It is also the centerpiece for various new intervention techniques. Their morphologic effect on the site of obstruction has been termed “remodeling.” Part V of this six-part series focuses on remodeling effects of balloon angioplasty on obstructed young (≤ 1 year) and old (> 1 year) saphenous vein bypass grafts.     

Collagen synthesis activities of chondrocytes from histologically distinct zones of chick embryo tibia

Monolayer cultures of 12-day chick embryo chondrocytes from the regions of dividing (zone 1), elongated (zone 2), and hypertrophied (zone 3) chondrocytes in the tibial cpiphyseal growth plate were analyzed for their capacity to synthesize types II, IX, X, and XI collagens. Synthesis of types II and IX collagens was markedly elevated in the zone 2 culture, while type X collagen synthesis was maximal in zone 3. Type XI collagen was synthesized at low rates in all cultures, with some elevation of its rate in zones 2 and 3. In terms of mol percent of total collagen synthesis, types II and IX collagens decreased from zone 1 to zone 3, while type X collagen increased progressively. Thus, the composition of the extracellular collagens produced by the different zones changed markedly during chondrocyte differentiation. In addition, type X collagen was released exclusively into the culture medium, whereas type XI collagen was retained in the extracellular cell-associated matrix. In contrast, types II and IX collagens were found in both the culture medium and the cell matrix pools. Although types II and IX collagens showed similar changes during differentiation, the synthetic molar ratios of these two collagens varied from 3 to 18 in different cultures, suggesting that the synthesis of these two products is not tightly coupled in these cells.