A concealed small bowel perforation in an adult secondary to bicycle handlebar trauma

Traumatic abdominal wall hernia (TAWH) secondary to bicycle handlebar is a rare injury. The majority of the literature describes abdominal wall herniation in children. We present a rare case of TAWH in an adult with a concealed small bowel perforation. Although clinical examination in conjunction with computed tomography can exclude the majority of solid organ injuries, small bowel injuries can often be missed. Our case initially revealed a serosal tear in the small bowel but, on close inspection, a separate 3mm perforation was identified, hidden in the small bowel mesentery. We strongly support a low threshold for operative intervention if there is any suspicion. Moreover, we stress the importance of meticulous examination during laparotomy as this injury could have been easily missed, resulting in potential morbidity or mortality in a patient sustaining such an injury.     

Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus

We have investigated the role of plasminogen activator inhibitor 1 (PAI- 1) in the regulation of fibrinolysis using a model thrombus composed of thrombin-stimulated platelets, fibrin(ogen), plasminogen, and recombinant tissue-type plasminogen activator. Laser light scattering kinetic measurements showed that clot lysis was significantly delayed both by thrombin-stimulated platelets and their cell-free releasate. This delay in lysis was almost fully reversed by the addition of a PAI- 1-specific monoclonal antibody that blocks the ability of PAI-1 to inhibit plasminogen activators. Lysis half-times exhibited a linear dependence on the concentration of PAI-1 antigen present, as determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecylsulfate- polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting confirmed the presence of PAI-1 antigen in the platelet releasates. Scanning electron micrographs of the model thrombus components sampled late in lysis showed considerable unproteolyzed fibrin still attached to platelets. Immunogold cytochemistry detected large amounts of PAI-1 antigen in the partially lysed platelet-fibrin thrombi. This PAI-1 appeared to be bound to the fibrin network rather than to the platelet surface itself. We conclude that the residual clots observed late in lysis represent platelet-associated fibrin to which platelet-released PAI-1 has bound, rendering it less susceptible to degradation.     

Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD,McKay RR,Werner L,Atkins MB,Van Allen EM,Olivier KM,Song J,Signoretti S,McDermott DF,Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503.

Background

Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Gut epithelial apoptosis after severe burn: effects of gut hypoperfusion

BACKGROUND: Severe cutaneous burn causes transient mesenteric vasoconstriction and altered gut mucosal integrity. We recently showed that burn also increases gut epithelial cell death by apoptosis. The goal of this study was to determine whether changes in gut perfusion after burn contribute to burn-associated gut apoptosis. STUDY DESIGN: We first correlated superior mesenteric artery blood flow with measurement of gut perfusion at the tissue level by laser doppler in four nonburned rats before, during, and after arterial clamping to validate our measurements of gut perfusion. We then characterized gut perfusion sequentially over time after burn; gut perfusion was measured 3 cm from the ligament of Treitz before burn and hourly for 6 hours. A group of control rats underwent the exact same protocol without the burn to exclude effects of anesthesia and laparotomy on tissue perfusion (n = 4). We studied a third group of rats with hypoperfusion of the same duration and magnitude induced mechanically without burn (n = 7). Sections of the proximal gut from all three groups (control without burn, burn, and hypoperfusion without burn) were examined for epithelial apoptosis. RESULTS: Linear regression analysis demonstrated a strong correlation between superior mesenteric artery blood flow and intestinal tissue perfusion measured by laser doppler under both low and high flow conditions (r = 0.85). Laser doppler measurements of gut perfusion after burn showed deceased gut perfusion that was maximal at 2 hours postburn (p < 0.05), and that persisted for 4 hours (p < 0.05). By 6 hours, gut perfusion returned to baseline. Apoptosis increased significantly in the burn group (2.11 +/- 0.17%) compared with control (0.52 +/- 0.2%) and the mechanically decreased perfusion group (0.51 +/- .03) (p < 0.001). CONCLUSIONS: We conclude that burn-induced gut hypoperfusion is insufficient to cause burn-related increased gut epithelial apoptosis. We speculate that the signal for increased gut epithelial apoptosis is primarily related to proinflammatory mediators induced by the burn wound.     

Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

BACKGROUND AND PURPOSE

Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.

EXPERIMENTAL APPROACH

The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.

KEY RESULTS

Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB₁) inverse agonist, {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 but were unaffected by the 5-HT_1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB₁ receptor antagonist, AM251, in addition to {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 and WAY100135.

CONCLUSIONS AND IMPLICATIONS

Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT_1A and CB₁ receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD.     

Laparoscopic Hartmann’s procedure: a viable option for treatment of acutely perforated diverticultis

Background  A laparoscopic technique for acutely perforated diverticulitis (i.e., laparoscopic Hartmann’s procedure) has not been described. The authors present their technique for laparoscopic sigmoid resection, end colostomy, and subsequent laparoscopic takedown of colostomy. Methods  A retrospective review of patients with Hinchey III/IV diverticulitis who underwent a laparoscopic Hartmann’s procedure was performed in this study. Laparoscopic takedown of sigmoid colostomy was performed 2 to 3 months later. Data from these procedures including estimated blood loss (EBL), length of the operative procedure, patient outcomes, and demographics were evaluated. Results  Seven patients with a mean age of 49.7 years underwent laparoscopic sigmoid colectomy with end colostomy. None of these patients had a history of diverticulitis. Their mean EBL was 138 ml, and their mean operative time was 154 min. None of the procedures required conversion to use of a hand port or conversion to open procedure. The average time to return of bowel function was 3.7 days, with one patient experiencing a postoperative ileus. The mean postoperative hospital stay was 6.6 days. There were no complications. Laparoscopic Hartmann’s takedown was performed for all the patients approximately 2 to 3 months later. The mean EBL was 107 ml, and the average operative time was 189 min. One patient had intraoperative anastomotic leak, which was successfully repaired and retested. Again, none of the procedures required the use of a hand port or a laparotomy. The average time to return of bowel function was 3.4 days. The average length of hospital stay was 5.3 days, with one patient experiencing a fat necrosis. Conclusions  Laparoscopic Hartmann’s procedure and laparoscopic takedown are technically feasible procedures with reasonable outcomes.     

Assessment of Survival and Clinical Benefit in Malignant Pleural Mesothelioma (MPM) Patients Treated with Gemcitabine and Carboplatin

Purpose: To evaluate the efficacy, safety, and clinical benefit of combined gemcitabine and carboplatin in patients with previously untreated malignant pleural mesothelioma (MPM). Patients and Methods: This prospective phase II study was performed on 42 eligible patients with histologically or cytologically proven MPM presenting to Ain Shams University hospitals and Sohag Cancer Center between January 2002 and April 2006. They were assigned to receive combined gemcitabine (1250mg/m2) on days, 1 and 8 and carboplatin (AUC 6) on day 1. The regimen was repeated every 21 days. The treatment continued until disease progression or intolerable drug toxicity. Results: The patients received a total of 227 cycles of chemotherapy (median 5.4 cycles and range from 2 to 9 cycles). The chemotherapy was generally well tolerated. Neutropenia, thrombocytopenia and anemia were the most severe (Grade 3 or 4) toxicities recorded during therapy and were reported in (14%), (9.5%), and (9.5%), respectively. Twelve patients (29%) achieved partial response, 18 patients (42%) had stable disease and the disease progressed in the remaining 12 patients (29%). The median follow-up duration was 11 months (range 5 from 20 months). The overall survival (OS) and progression free survival (PFS) at one year was 44.5% and 33.2%, respectively. The median survival and time to disease progression were 11 months and 8.5 months respectively. Of 32 patients assessed for clinical benefit, 20 patients (62.5%) were considered clinical benefit responders. Conclusion: The combination of gemcitabine and carboplatin is a safe and tolerable treatment with reasonable response rate, OS, and PFS compared with the historical phase II single agents and combined chemotherapy studies in patients with MPM. Key Words: Mesothelioma , Gemcitbine , Carboplatin.