Usefulness of Ultrasound in Evaluating the Diaphragm in Neonates and Infants With Congenital Diaphragmatic Hernias

This report describes the evaluations of 2 patients with congenital diaphragmatic hernias using ultrasound (US). Identifying the size of the diaphragmatic defect is important when determining the type of surgical repair required. In case 1, the US evaluation of a Bochdalek hernia showed the rim of the anterolateral diaphragm; therefore, thoracoscopic primary repair was performed. In case 2, (Morgagni‐Larrey hernia), US revealed the left side of a retrosternal diaphragmatic hernia sac; therefore, thoracoscopic repair from the left thorax was performed. Ultrasound was useful for detecting the location and defect size of the diaphragmatic hernia and determining optimal surgical management.     

Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2)

It is well known that bone marrow contains mesenchymal stromal cells (MSCs), which can show osteoblastic differentiation when cultured in osteogenic medium containing ascorbic acid, beta-glycerophosphate and dexamethasone. The differentiation results in the appearance of osteoblasts, together with the formation of bone matrix; thus, in vitro cultured bone (osteoblasts/bone matrix) could be fabricated by MSC culture. This type of cultured bone has already been used in clinical cases involving orthopaedic problems. To improve the therapeutic effect of the cultured bone, we investigated the culture conditions that contributed to extensive osteoblastic differentiation. Rat bone marrow was primarily cultured to expand the number of MSCs and further cultured in osteogenic medium for 12 days. The culture was also conducted in a medium supplemented with either bone morphogenetic protein-2 (BMP-2) or fibroblast growth factor (FGF-2), or with sequential combinations of both supplements. Among them, the sequential supplementation of FGF-2 followed by BMP-2 showed high alkaline phosphatase activity, sufficient bone-specific osteocalcein expression and abundant bone matrix formation of the MSC culture. These data implied that the number of responding cells or immature osteoblasts was increased by the supplementation of FGF-2 in the early phase of the culture and that these cells can show osteoblastic differentiation, of which capability was augmented by BMP-2 in the late phase. The sequential supplementation of these cytokines into MSC culture might be suitable for the fabrication of ideal cultured bone for use in bone tissue engineering.     

Activation of PAR‐2 Elicits NO‐Dependent and CGRP‐Independent Dilation of the Dural Artery

(Headache 2010;50:1017‐1030) Objectives.— The goal of this study was to determine the vascular effects of protease‐activated receptor‐2 (PAR‐2) activation in the rat cranial vasculature. Background.— The role of PAR‐2 in pain and inflammatory conditions has been established but the information available on its effects and receptor distribution in the trigeminal vascular axis is limited. We studied the dilatory function and expression of PAR‐2 in the neuro‐vascular circuit, critical in migraine pathogenesis. We also investigated the interaction of PAR‐2 with calcitonin gene‐related peptide (CGRP) and dural mast cells. Methods.— We used an improved model of intravital microscopy on the closed cranial window in rats to study the vascular effects of PAR‐2 activating peptides (PAR‐2 APs; SLIGRL‐NH₂, 2‐Furoyl‐LIGRLO‐NH₂) in the dural vasculature. Measurement of immunoreactive CGRP in skull halves and in trigeminal nucleus caudalis was done by using an enzyme‐linked immunosorbent assay. We also analyzed the presence of PAR‐2 in different migraine relevant tissues by quantitative real‐time PCR and Western blot analysis. Results.— PAR‐2 APs and trypsin induced a dose‐dependent increase in dural artery diameter. The topical application of a nonspecific nitric oxide synthase (NOS) inhibitor, L‐N^G‐Nitroarginine methyl ester, attenuated SLIGRL‐NH₂ responses. Olcegepant, a CGRP receptor antagonist, did not a have significant effect on the SLIGRL‐NH₂ responses, though exogenous CGRP responses were completely blocked. There was no significant release of CGRP from skull halves incubated with SLIGRL‐NH₂ as compared with those incubated with the corresponding negative peptide. Chronic mast cell degranulation did not change the vascular effects of PAR‐2 APs. mRNA and protein expression of PAR‐2 were found throughout trigeminovasuclar axis. Conclusion.— PAR‐2 activation leads to vasodilation of dural arteries and these responses are partially mediated by nitric oxide. As PAR‐2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism.     

(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)

(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, Brivudin, Zostex, Zerpex, Zonavir), now more than 20 years after its discovery, still stands out as a highly potent and selective inhibitor of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) infections. It has been used in the topical treatment of herpetic keratitis and recurrent herpes labialis and the systemic (oral) treatment of herpes zoster (zona, shingles). The high selectivity of BVDU towards HSV-1 and VZV depends primarily on a specific phosphorylation of BVDU to its 5'-diphosphate (DP) by the virus-encoded thymidine kinase (TK). After further phosphorylation (by cellular enzymes), to the 5'-triphosphate (TP), the compound interferes as a competitive inhibitor/alternate substrate with the viral DNA polymerase. The specific phosphorylation by the HSV- and VZV-induced TK also explains the marked cytostatic activity of BVDU against tumor cells that have been transduced by the viral TK genes. This finding offers considerable potential in a combined gene therapy/chemotherapy approach for cancer. To the extent that BVDU or its analogues (i.e., BVaraU) are degraded (by thymidine phosphorylase) to (E)-5-(2-bromovinyl)uracil (BVU), they may potentiate the anticancer potency, as well as toxicity, of 5-fluorouracil. This ensues from the direct inactivating effect of BVU on dihydropyrimidine dehydrogenase, the enzyme that initiates the degradative pathway of 5-fluorouracil. The prime determinant in the unique behavior of BVDU is its (E)-5-(2-bromovinyl) substituent. Numerous BVDU analogues have been described that, when equipped with this particular pharmacophore, demonstrate an activity spectrum characteristic of BVDU, including selective anti-VZV activity.     

Ultrasound‐guided reduction of an incarcerated obturator hernia in an elderly patient

Obturator hernia is a rare but clinically relevant cause of intestinal obstruction, usually found in elderly, thin, multiparous women. It is difficult to diagnose, leading to diagnostic delay with a high incidence of strangulation and a high mortality rate. Surgery is the only reported treatment. We report the case of an 86‐year‐old woman, in whom an early diagnosis of incarcerated obturator hernia was made with subsequent reduction by compression with an ultrasound transducer. When the risk of strangulation is presumed to be low, ultrasound‐guided reduction of an obturator hernia is achievable and worth considering.     

IL-2 gene C/T polymorphism is associated with prostate cancer

Cytokines are reported to be associated with the formation of prostate cancer. Our aim was to investigate whether C/T polymorphisms of the interleukin-2 (IL-2) gene and IL-2 receptor beta (IL-2RB) gene are associated with prostate cancer. We compared the frequency of the polymorphisms of the IL-2 gene and the IL-2RB gene between 96 patients with prostate cancer and 105 healthy male volunteers from the same area (age >60 years). They were followed for at least 5 years. There was a significant difference in distribution of the genotype of the IL-2 gene polymorphism between the prostate cancer group and the control group (P = 0.017). The distribution of the TT homozygote of the IL-2 gene was significantly higher in the cancer group (32.3%) than in the control group (16.2%). However, no significant statistical difference was found between the polymorphism of the IL-2 gene and prostate cancer in survival analysis during a 5-year follow up period (log rank test; P = 0.19). There was no significant difference in the distribution of the genotype of the IL-2RB gene polymorphism between controls and cancer patients (P = 0.388). This study suggests that the IL-2 gene may be associated with susceptibility to prostate cancer in the Taiwan population.     

Short‐term outcome of single‐incision laparoscopic totally extra‐peritoneal inguinal hernia repair

We performed single‐incision laparoscopic surgery for totally extra‐peritoneal (SILS‐TEP) repair using a lightweight mesh fixed by absorbable tacks and without balloon dilation. Thirty‐four patients (mean age, 66.5 years) underwent SILS‐TEP repair in our hospital between September 2011 and April 2012; 30 patients had unilateral hernia and 4 had bilateral hernias. Mean operative time was 85.6 min for unilateral hernia and 137.7 min for bilateral hernias. All patients underwent successful SILS‐TEP repair. Mean hospital stay was 3.4 days. Mean duration of follow‐up was 7.1 months. Four seromas were observed, but no recurrences or major complications occurred. SILS‐TEP is an economical and useful method for decreasing postoperative complications, such as neuralgia and recurrence, and it could be an attractive approach for inguinal hernia.     

腹股沟疝Lichtenstein修补术与腹膜前修补术的对照研究

目的比较腹股沟疝Lichtenstein修补术与腹膜前修补术这两种腹股沟疝修补术的优缺点。方法回顾性分析2005年1月至2008年12月行Lichtenstein修补术患者114例和腹膜前修补术152例手术时间、住院时间、术后不适感、术后并发症、复发等资料。结果两种术式在住院时间、术后并发症、复发率等方面差异无统计学意义;Lichtenstein修补术手术时间较腹膜前修补术短,但术后不适感主诉较多;腹膜前修补的费用较高。结论两种术式各有优缺点,均可用于腹股沟疝的修补。     

Lumiracoxib (Prexige): a new selective COX-2 inhibitor

Lumiracoxib, a new selective COX-2 inhibitor, has been recently approved in England and Mexico for the treatment of acute and chronic pain. Although it is the fifth COX-2 inhibitor to come to the market, it has a unique structure that could prove to be important in the adverse event profile. Double blind randomised trials have proved its efficacy in acute pain, dysmenorrhea, rheumatoid arthritis and osteoarthritis. Its gastrointestinal safety profile has been studied in multiple trials. The main clinical trail, therapeutic arthritis research and gastrointestinal event trial, has as primary end point: perforations, obstructions and bleeding and as secondary end points: cardiovascular, renal and hepatic safety profile. The results of this trial will probably change the way we look at selective COX-2 inhibitors.     

腹膜前间隙疝修补术与疝环充填式疝修补术治疗老年腹股沟疝患者的临床效果比较

目的比较腹膜前间隙疝修补术与疝环充填式疝修补术治疗老年腹股沟疝患者的临床效果。方法将80例老年腹股沟疝患者根据手术方案不同分为观察组与对照组,各40例。观察组采取腹膜前间隙疝修补术治疗,对照组采取疝环充填式疝修补术治疗。比较两组的治疗效果。结果观察组的手术时间、术后离床活动时间、术后疼痛持续时间、住院时间均短于对照组,术中失血量少于对照组(P<0.05)。观察组的异物感、切口感染发生率低于对照组(P<0.05)。观察组的术后复发率低于对照组(P<0.05)。结论腹膜前间隙疝修补术治疗老年腹股沟疝患者的临床效果显著,有利于降低并发症发生率及复发率,同时能够减少手术创伤并优化围术期指标。     

Rare case of a right Bochdalek hernia with retroperitoneal prolapse of organs into the thoracic cavity in infancy: A case report

We report an extremely rare case of a right Bochdalek hernia with a sac, in which the retroperitoneal and intra-abdominal organs prolapsed into the thoracic cavity at the same time. The patient was a 7-month-old female with no comorbidities. She presented with cough and fever, and chest radiography revealed a right diaphragmatic hernia. Computed tomography showed that the right kidney, intestine, colon, and liver had prolapsed into the thoracic cavity. The patient underwent thoracoscopic surgery, which showed that the abdominal and retroperitoneal organs prolapsed into the thoracic cavity through the Bochdalek hernia. The herniated organs were spontaneously reduced using thoracoscopic insufflation. The defect hole was closed with artificial mesh. We adopted a thoracoscopic approach, in terms of easy reduction of herniated organs and accurate evaluation of the hernia orifice, which was useful.     

A 3-Month-Old Female with an Inguinal Mass

Background: Inguinal masses are a common finding among infants. The differential diagnosis of these masses in infants is broad, with inguinal hernia being the most common diagnosis in both males and females. However, the evaluation and management of males vs. females with inguinal masses is somewhat different due to the greater potential for gonad involvement in males. Objectives: The pathophysiology and management of inguinal hernias is discussed with a specific focus on inguinal hernias in females. Case Report: We present a case of a 3-month-old girl with an inguinal hernia and a mass, found to be an incarcerated ovary. Conclusions: Inguinal masses in infancy are common, with inguinal hernia being the most common cause by far. A female infant with suspected inguinal hernia should be thoroughly evaluated to determine whether ovarian content is present.     

Periodontal regeneration using an injectable bone cement combined with BMP‐2 or FGF‐2

Periodontitis is a frequently diagnosed oral disease characterized by bone resorption and soft tissue loss around teeth. Unfortunately, currently available therapies only slow or arrest progress of the disease. Ideally, treatment of periodontal defects should be focused on complete regeneration of the lost tissues [(bone and periodontal ligament (PDL)]. As a result, this study used intrabony defects to evaluate the regenerative potential of an injectable macroporous calcium phosphate cement (CaP) in combination with bone morphogenetic protein‐2 (BMP‐2) or fibroblast growth factor‐2 (FGF‐2). After creating 30 periodontal defects in 15 Wistar rats, three treatment strategies were conducted: application of CaP only, CaP + BMP‐2 and CaP + FGF‐2. Animals were euthanized after 12 weeks and processed for histology and histomorphometry. Using CaP alone resulted in limited effects on PDL and bone healing. CaP + BMP‐2 showed a good response for bone healing; a significant 2.4 fold increase in bone healing score was observed compared to CaP. However, for PDL healing, CaP + BMP‐2 treatment showed no difference compared to the CaP group. The best results were observed with the combined treatment of CaP + FGF‐2, which showed a significant 3.3 fold increase in PDL healing score compared to CaP + BMP‐2 and a significant 2.6 fold increase compared to CaP. For bone healing, CaP + FGF‐2 showed a significant 1.9 fold increase compared to CaP but no significant difference was noted compared to the CaP + BMP‐2 group. The combination of a topical application of FGF‐2 and an injectable CaP seems to be a promising treatment modality for periodontal regeneration. Copyright © 2012 John Wiley & Sons, Ltd.     

The endocannabinoid 2‐arachidonoylglycerol activates human platelets through non‐CB1/CB2 receptors

Summary. Background: The endocannabinoid 2‐arachidonoylglycerol (2‐AG) is an endogenous lipid that acts through the activation of G‐protein‐coupled cannabinoid receptors and plays essential roles in many physiological contexts. In the cardiovascular system 2‐AG is generated by both activated endothelial cells and platelets, and participates in the regulation of inflammation and thrombosis. Although human platelets actively metabolize endocannabinoids, 2‐AG also binds to platelet surface and leads to cell activation. Objective: To investigate the biological consequence of 2‐AG interactions with human platelets and to clarify the role of cannabinoid receptors. Methods: Gel‐filtered platelets were stimulated with 2‐AG in the presence or absence of various inhibitors. Platelet aggregation and secretion were measured in a lumiaggregometer. Calcium ion movements were measured in FURA‐2 loaded platelets. Thromboxane A₂ (TxA₂) generation was evaluated as Thromboxane B₂ accumulation with a commercial EIA assay. Results: 2‐AG induced platelet shape change, aggregation and secretion with a dose‐dependent mechanism that required engagement of platelet TxA₂ receptors. 2‐AG caused also cytosolic calcium increase; however, it was totally dependent on availability of TxA₂. Indeed 2‐AG was able to induce a robust generation of TxA₂ through the cyclooxygenase pathway. Treatment of platelets with inhibitors of monoacylglycerol lipase and fatty acid amide hydrolase did not affect the activation induced by 2‐AG. Moreover, neither CB₁ and CB₂ proteins nor CB₁/CB₂ mRNAs were detected in platelets. Conclusions: 2‐AG can be considered a new physiologic platelet agonist able to induce full platelet activation and aggregation with a non‐CB₁/CB₂ receptor‐mediated mechanism.     

Inhibitors of Microsomal Prostaglandin E2 Synthase‐1 Enzyme as Emerging Anti‐Inflammatory Candidates

Cyclooxygenases (COX‐1 and COX‐2) catalyze the conversion of arachidonic acid (AA) into PGH₂ that is further metabolized by terminal prostaglandin (PG) synthases into biologically active PGs, for example, prostaglandin E₂ (PGE₂), prostacyclin I₂ (PGI₂), thromboxane A₂ (TXA₂), prostaglandin D₂ (PGD₂), and prostaglandin F₂ alpha (PGF_2α). Among them, PGE₂ is a widely distributed PG in the human body, and an important mediator of inflammatory processes. The successful modulation of this PG provides a beneficial strategy for the potential anti‐inflammatory therapy. For instance, nonsteroidal anti‐inflammatory agents (NSAIDs), both classical nonselective (cNSAIDs) and the selective COX‐2 inhibitors (coxibs) attenuate the generation of PGH₂ from AA that in turn reduces the synthesis of PGE₂ and modifies the inflammatory conditions. However, the long‐term use of these agents causes severe side effects due to the nonselective inhibition of other PGs, such as PGI₂ and TXA₂, etc. Microsomal prostaglandin E₂ synthase‐1 (mPGES‐1), a downstream PG synthase, specifically catalyzes the biosynthesis of COX‐2‐derived PGE₂ from PGH₂, and describes itself as a valuable therapeutic target for the treatment of acute and chronic inflammatory disease conditions. Therefore, the small molecule inhibitors of mPGES‐1 would serve as a beneficial anti‐inflammatory therapy, with reduced side effects that are usually associated with the nonselective inhibition of PG biosynthesis.