Laparoscopic colectomy for colonic polyps

Background  Benign colonic polyps not amenable to colonoscopic resection or those containing carcinoma require surgical excision. Traditionally, formal colectomy with clearance of the lymphatic basin has been performed. The aim of this study was to review our experience with the laparoscopic approach for retrieval of colonic polyps with specific emphasis on safety, feasibility, and tumor localization. Methods  Retrospective chart review of all patients who underwent laparoscopic colectomy for colonic polyps was performed. Initial colonoscopic biopsies were compared with the postoperative pathology report of the resected specimen. Results  Forty-nine patients (22 males, 27 males, mean age 66 years) underwent laparoscopic colectomy for colonic polyps. Indications for surgery were presumably benign polyps in 38 patients, and superficial carcinoma in a polyp, diagnosed by colonoscopy, in 11; twenty-three patients underwent preoperative localization procedures. In 19% of patients who did not have preoperative localization, difficulties locating the polyp were encountered during surgery, requiring intraoperative endoscopy or conversion to laparotomy. In 7 of the 38 patients with presumably benign lesion, colon cancer was diagnosed in the colectomy specimen. None of the 18 patients who had cancerous lesions had any positive lymph nodes. Conclusions  Laparoscopic surgery for the treatment of colonic polyps seems to be feasible and safe, with a low complication rate. Tumor localization is crucial for adequate resection. Although one-fifth of presumably benign polyps harbored cancer, none of these patients had positive lymph nodes. These preliminary results may question the need for radical lymph node clearance in these patients. Poster presentation at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Dallas, TX, USA, April 26–29, 2006. Poster presentation at the annual meeting of the European Society for Endoscopic Surgeons (EAES), Berlin, Germany, September 13–16, 2006.     

Regulatory T cells: prospective for clinical application in hematopoietic stem cell transplantation

PURPOSE OF REVIEW: Regulatory T cells exert a dominant effect in controlling autoimmunity and maintaining peripheral tolerance. Regulatory T cells are also involved in preventing allograft rejection and graft versus host disease. Cellular therapy with expanded regulatory T cells represents a promising approach to control T-cell mediated pathology. In this review we will summarize the efforts to design new methods for expanding regulatory T cells and exploit their regulatory function as cellular therapy for the treatment of graft versus host disease after hematopoietic stem cell transplantation. RECENT FINDINGS: Among CD4+ T cells, the best described are the naturally occurring CD4+CD25+ regulatory T cells and type 1 regulatory T cells. Recent progress has been made in the characterization of both subsets in terms of isolation and induction, respectively. However, a clear definition of their mechanisms of action has still to be achieved. SUMMARY: Better understanding of the mechanisms of suppression mediated by regulatory T cells might enable their use to modulate specific immune responses. Moreover, the recent development of methods allowing the ex-vivo expansion of regulatory T cells, to provide sufficient number of cells for in-vivo infusion, represents the first step toward the use of these cells as cellular therapy for the treatment of immunologic and hematological diseases.     

Stone Age hut in Israel yields world's oldest evidence of bedding

The earliest archaeological remains of dwelling huts built by Homo sapiens were found in various European Upper Paleolithic open-air camps. Although floors of huts were found in a small number of cases, modern organization of the home space that includes defined resting areas and bedding remains was not discovered. We report here the earliest in situ bedding exposed on a brush hut floor. It has recently been found at the previously submerged, excellently preserved 23,000-year-old fisher-hunter-gatherers' camp of Ohalo II, situated in Israel on the shore of the Sea of Galilee. The grass bedding consists of bunches of partially charred Puccinellia confer convoluta stems and leaves, covered by a thin compact layer of clay. It is arranged in a repeated pattern, on the floor, around a central hearth. This study describes the bedding in its original context on a well preserved intentionally constructed floor. It also reconstructs on the basis of direct evidence (combined with ethnographic analogies) the Upper Paleolithic hut as a house with three major components: a hearth, specific working locales, and a comfortable sleeping area near the walls.     

Energy landscape of amyloidogenic peptide oligomerization by parallel-tempering molecular dynamics simulation: significant role of Asn ladder

Recent evidence suggests that amyloidogenic oligomers may be the toxic species in cell cultures. Thus, it is crucial to understand their structure and oligomerization mechanism in atomistic detail. By employing tens of fast central processing units and an advanced phase-space sampling algorithm, parallel-tempering molecular dynamics, we have explored the energy landscape of amyloidogenic peptide oligomerization in explicit water. A pentapeptide, DFNKF, derived from human calcitonin and its mutant, DFAKF, was simulated with a total simulation time of approximately 500 ns. The detailed oligomerization process of a DFNKF parallel beta-sheet formation at 300 K has been characterized. The assembly of a parallel beta-sheet from the amorphous state mainly occurs via a "bottleneck" channel where the interstrand Asn-Asn stacking is the major interaction. The interactions of Asn-Asn stacking include both backbone and side-chain hydrogen bonds. The Asn-Asn interactions work like "glue" by sticking the DFNKF strands together and assist the "on-pathway" oligomerization. The Asn-Asn stacking observed here is similar to the Asn ladder commonly found in globular beta-helix proteins. A control run shows that when Asn is mutated to Ala, the stability and population of the DFAKF parallel beta-sheet is decreased. Furthermore, our in vitro mutagenesis experiments show that the ability of DFAKF peptides to form amyloid fibrils is significantly reduced, in agreement with the simulations. Knowledge of the energy landscape of oligomerization may provide hints for rational drug design, preventing amyloid-associated diseases.     

Peripartum hypertension from pheochromocytoma: a rare and challenging entity

BACKGROUND: Pheochromocytoma, a rare and usually curable cause of hypertension, is characterized by symptoms and signs related to increased catecholamine secretion. Pregnancy can elicit clinical manifestations of otherwise unrecognized pheochromocytoma. METHODS AND RESULTS: Four women, ranging in age from 27 to 37 years, were referred to the hypertension clinic with the following presentations: 1) a 35-year-old woman, diagnosed with gestational hypertension and headaches during the third trimester of her pregnancy and 5 months after delivery, was hospitalized with pulmonary edema. Echocardiography revealed severe dilated left ventricular (LV) dysfunction. Cardiac function was normalized after surgical resection of a pheochromocytoma from her left adrenal; 2) a 37-year-old woman suffered from preeclampsia, persistent hypertension and orthostatic hypotension after a cesarean section. A diagnostic work-up revealed a catecholamine-secreting paraganglioma in the retroperitoneum. The patient underwent a laparosopic resection of the tumor; 3) a 27-year-old woman suffered from hypertension and episodes of palpitations, sweating, and dyspnea in the first trimester of her pregnancy. An ultrasound revealed a 5-cm mass in the left adrenal. She underwent a left adrenalectomy at the 17th week of pregnancy, which confirmed the diagnosis of pheochromocytoma; 4) a 34-year-old woman, at the 26th week of pregnancy, presented with an acute loss of vision and blood pressure of 230/140 mm Hg. Fundoscopy showed papilledema with soft exudates in both eyes. Chemical studies were positive and imaging revealed a left adrenal pheochromocytoma. Despite aggressive medical treatment, fetal distress mandated a laparotomy at the end of the 28th week of pregnancy. A healthy newborn was delivered and resection of the adrenal tumor confirmed the diagnosis of pheochromocytoma. CONCLUSIONS: Although rare, pheochromocytoma can cause severe peripartum hypertension. Screening for pheochromocytoma, ideally with plasma-free metanephrines, should be considered in cases of peripartum hypertension.     

Future strategies for the treatment of diastolic heart failure

It is estimated that 30% to 50% of heart failure patients have preserved systolic left ventricular (LV) function, often referred to as diastolic heart failure (DHF). Mortality is high in this patient population, and morbidity and rate of hospitalization are similar to those of patients with systolic heart failure. The management of patients with diastolic heart failure is essentially empirical, limited, and disappointing. New drugs, devices, and gene therapy based treatment options are currently under investigation. In this review, future strategies for the treatment of diastolic heart failure are discussed.     

Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/- 2.7%, p = 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteine-lowering, but does not modulate markers of inflammation.