How to avoid recurrence in Lichtenstein tension-free hernioplasty

The following key principles of the Lichtenstein tension-free hernioplasty can help avoid recurrence and decrease postoperative pain: (1) Use a large sheet of mesh that will extend approximately 2 cm medial to the pubic tubercle, 3 to 4 cm above Hesselbach's triangle, and 5 to 6 cm lateral to the internal ring. (2) Cross the tails of the mesh behind the spermatic cord to avoid recurrence lateral to the internal ring. (3) Secure the mesh with two interrupted sutures on the upper edge and one continuous suture with no more than 3 to 4 passes on the lower edge of the mesh to prevent folding and movement of the mesh in the groin. (4) Position the mesh in a slightly relaxed dome shape configuration to counteract the forward protrusion of the transversalis fascia when the patient stands up from the intraoperative supine position. (5) Identify and protect the ilioinguinal, iliohypogastric, and genital nerves throughout the operation.     

Natural retinoids inhibit proliferation and induce apoptosis in pancreatic cancer cells previously reported to be retinoid resistant

BACKGROUND: The anticancer ability of natural retinoids on pancreatic adenocarcinoma, an aggressive tumor, is still controversial. This investigation tested the hypothesis that all-trans retinoic acid can inhibit proliferation and induce apoptosis in pancreatic cancer cell lines. MATERIALS AND METHODS: Using our previously optimized conditions, the effect of all-trans retinoic acid (atRA, 0.001-10 microM) was tested in ten human pancreatic adenocarcinoma cell lines with various degrees of differentiation. Proliferation was monitored by cell number, [3H]-thymidine incorporation and cell cycle arrest. Apoptosis was investigated morphologically by light and electron microscopy and biochemically by tissue transglutaminase activity (TGase), mitochondrial membrane potential, cell cycle analysis of sub-G1 cells and detection of fragmented DNA (fragmentation of prelabeled DNA, agarose electrophoresis and TUNEL assays). RESULTS: Retinoic acid caused potent concentration- and time-dependent inhibition of proliferation of all cell lines studied. Cell cycle was arrested at G1 or G2 with extensive reduction of number of cells at S-phase after 24 hours of treatment with apoptotic concentration of atRA. Complete inhibition of proliferation was followed by apoptosis as indicated by the progressive accumulation of sub-G1 apoptotic cells which was confirmed by the more specific DNA fragmentation assays. There were extensive apoptosis-indicative light and electron microscopic changes preceded by phenotypic redifferentiation. TGase was induced between 3-5-fold the control level and its inhibition partially reversed the antiproliferative effect of atRA. Cellular viability during the preapoptotic stage was confirmed by normal mitochondrial membrane potential in the first two days of treatment with the maximum atRA concentration used. However, the potential was progressively reduced with time as a preapoptotic change. Caspase 3-like activity was induced by the apoptotic concentrations of atRA at late time points. However, the redifferentiation indicative changes were not prevented by cotreatment with Ac-DEVE-CHO caspase 3 inhibitor. CONCLUSIONS: Together, our results demonstrated the efficient anticancer ability of natural retinoids on human pancreatic cancer cell lines tested, even those previously reported to be retinoid resistant.     

High concentrations of retinoids induce differentiation and late apoptosis in pancreatic cancer cells in vitro

Background: Our previous investigations showed that retinoids, at specific concentrations, can inhibit cell proliferation. In this investigation, we hypothesize that high concentrations of retinoids can induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. Materials and methods: To test our hypothesis, retinoid-induced differentiation was assessed: (1) phenotypically by light and electron microscopy and (2) biochemically by measuring carbonic anhydrase, aerobic metabolic and mucin producing activities. Modulation of transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) autocrine pathways were utilized as mechanistic and differentiation markers. Results: The extensive differentiation-indicative phenotypic changes correlated with several folds increase in the aerobic metabolism (MTT reduction and Mitochondrial mass), carbonic anhydrase activity and mucin production. There was a marked increase in TGF-beta (Bioassay and ELISA) and TGF-beta (RIA) secretion. EGF receptor density (Receptor binding assay) was reduced by 50% within six hours and was reflected on abolishment of EGFR ligand-induced proliferation. Cotreatment with the RAR-alpha antagonist, Ro41-5253 or pan-TGF-beta neutralizing antibody abolished the phenotypic and antiproliferative effects of all-trans retinoic acid. Apoptosis (TUNEL assay) was undetectable after three days of treatment with the maximum concentration used. However, apoptosis was extensively induced after six days of treatment. Conclusions: High concentrations of retinoids were able to induce phenotypic changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro. The clinical ramifications of these observations await further investigations.     

The effect of nonoxynol-9 on human endometrium

Contraceptive microbicides formulated as vaginal gels offer the possibility of women-controlled contraception and prevention of HIV infection. However, the effects of these gels on the upper reproductive tract is largely unknown. The purpose of this study was to determine the effects of nonoxynol-9 (N-9) on human endometrium. Human endometrial biopsies were cultured and incubated with various dosages of N-9 for 6 or 24 h. Endometrial histology was assessed by light microscopy using hematoxylin and eosin. Inflammatory response was determined by analyzing proinflammatory cytokines with enzyme-linked immunosorbent assay. Endometrial mucin was assessed by immunohistochemistry and real-time polymerase chain reaction. Histological changes consistent with focal coagulative necrosis were seen after 6 and 24 h of culture. All cytokines (interleukin 1beta, tumor necrosis factor alpha and interleukin 8) decreased at all concentrations of N-9 after 24 h of incubation. The expression of Mucin1 (MUC-1) was inhibited in a dose-dependent manner at both the protein and messenger RNA levels. These results demonstrate for the first time that N-9 has multiple, potential deleterious effects on the human endometrium characterized by necrosis, alteration of proinflammatory cytokines and inhibition of MUC-1 expression. Taken together, these in vitro findings suggest that N-9 can interrupt the functional barrier provided by the endometrium and, thus, facilitate infection with HIV and other pathogens.     

Transantral sphenopalatine artery ligation

Posterior epistnxis from branches of the sphenopalatine artery can be rapidly and effectively controlled by a new ligation technique. The sphenopalatine artery or its branches arc directly ligated as they exit the sphenopalatine foramen to enter the nose, completely avoiding the pterygomaxillary fossa. The vessels are exposed via a transantral approach, through the posterior portion of the medial antral wall. The mucoperiosteum of the lateral wall of the nose (medial antral wall) is preserved, elevated medially and posteriorly and used to tense the sphenopalatine vessels, bringing them into view and accessible for ligation at the foramen. Advantages of this technique include direct, specific ligation of the end vessels; ease and speed of operation; and avoidance of complications associated with the pterygomaxillary space. The technique was defined in multiple dissections of anatomic specimens and has been successful to date in 14 cases of severe posterior epistaxis.     

A case of seasonal bipolar disorder exacerbated by Cushing's disease

While depression is common in Cushing's syndrome from whatever cause (pituitary, adrenal, or ectopic adrenocorticotropic hormone-secreting tumor or hyperplasia, or exogenous administration of glucocorticoids) and hypercortisolemia is prevalent in major depression, any association between seasonal affective disorder and Cushing's syndrome is unknown. We present a case of seasonal bipolar disorder, gradually worsening for more than 9 years (1985-1994), accompanied by increasing osteoporosis, mild weight gain, and slight truncal obesity in a middle-aged woman. In January 1991, her seasonal affective disorder was successfully treated with light therapy, but in the following year, bipolar mood swings with a seasonal pattern emerged, which were refractory to light therapy and antidepressants but responsive to lithium. In August 1992, she became depressed despite a 1500-mg lithium daily dosage along with light therapy, and, in 1993, a diagnosis of Cushing's disease (Cushing's syndrome as a result of a pituitary adrenocorticotropic hormone-secreting tumor) was made. The pituitary tumor was removed in February 1994, and pituitary function was fully restored by 1996. While the symptoms of Cushing's syndrome subsided, her bipolar illness continued to require maintenance treatment with low doses of lithium but did not require light therapy.