Laparoscopic incisional hernia repair is feasible and safe after liver transplantation

Incisional hernia is a common complication after liver transplantation. The current study evaluated incidence and risk factors for incisional hernia and compared laparoscopic and open hernia repair in terms of feasibility and outcome.

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Laparoscopic ventral hernia repair is safe and cost effective

BACKGROUND: Ventral hernia repair is increasingly performed by laparoscopic means since the introduction of dual-layer meshes. This study aimed to compare the early complications and cost effectiveness of open hernia repair with those associated with laparoscopic repair. METHODS: Open ventral hernia repair was performed for 92 consecutive patients using a Vypro mesh, followed by laparoscopic repair for 49 consecutive patients using a Parietene composite mesh. RESULTS: The rate of surgical-site infections was significantly higher with open ventral hernia repair (13 vs 1; p = 0.03). The median length of hospital stay was significantly shorter with laparoscopic surgery (7 vs 6 days; p = 0.02). For laparoscopic repair, the direct operative costs were higher (2,314 vs 2,853 euros; p = 0.03), and the overall hospital costs were lower (9,787 vs 7,654 euros; p = 0.02). CONCLUSIONS: Laparoscopic ventral hernia repair leads to fewer surgical-site infections and a shorter hospital stay than open repair. Despite increased operative costs, overall hospital costs are lowered by laparoscopic ventral hernia repair.

The feasibility, efficacy and functional outcome of local anaesthetic repair of anterior and posterior vaginal wall prolapse

INTRODUCTION: Urogenital prolapse is a very common condition in women with a prevalence of 30%. If conservative therapy fails or is not desired by the patient, prolapse repair is usually performed under general or regional anaesthetic. The aim of the study was to evaluate feasibility, efficacy and functional outcome after fascial prolapse repairs under local anaesthetic (LA). PATIENTS AND METHODS: Between November 1999 and December 2000, 130 consecutive patients presenting with anterior or posterior prolapse or both were invited to have their procedure performed under LA. All patients with a symptomatic minimum stage II prolapse were included. Prior to surgery all women completed a standardized questionnaire examining the specific and non-specific symptoms of prolapse and their situation was classified using the ICS Pelvic Organ Prolapse (POP-Q) system. Follow up was 30 months. Objective success was defined as a stage 1 or less and no symptoms of bulge, subjective success was defined as lack of specific or non-specific symptoms of prolapse. RESULTS: There were 128 patients who agreed to have their operations performed under LA: 68 in the anterior group, 52 in the posterior group and 8 with a combined anterior and posterior repair. Objective cure rate was 88% for posterior repair, 87% for anterior repair and 63% for combined repair. Success rates were no different in primary from recurrent cases. There were no intraoperative complications and operating time was 21 min (anterior repair) or 23 min (posterior repair). There was no de novo postoperative urinary or stool incontinence and all patients but two would have the operation performed again under the same circumstances. The two remaining refused due to embarrassment but for no other reason. CONCLUSION: Local anaesthetic prolapse repair is feasible and effective in middle term results. It is well accepted by the patients who benefit from less side effects and short hospital stay.

Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain

Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0.001), tocopherols (P < 0.001) and glutathione (P < 0.001), and a decrease in superoxide dismutase activity (P = 0.005) in the liver, while protein oxidation was significantly increased (P = 0.011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0.001), but in contrast to the liver, ascorbate oxidation (P = 0.034), lipid oxidation (P < 0.001), DNA oxidation (P = 0.13) and DNA incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

Treatment of experimental cryptococcal meningitis with fluconazole: impact of dose and addition of flucytosine on mycologic and pathophysiologic outcome

Fluconazole is effective in the therapy of cryptococcal meningitis in patients with AIDS. The optimal dosage of fluconazole and the impact of combination with flucytosine are not known. In this study, rabbits with experimental cryptococcal meningitis were given fluconazole at low, intermediate, or high dose or in combination with a low or intermediate dose of flucytosine. Serial cerebrospinal fluid (CSF) examinations showed that all three doses of fluconazole and low-dose fluconazole in combination with intermediate-dose flucytosine were effective in reducing CSF cryptococcal titer, lactate, white blood cell count, and cryptococcal antigen (CRAG) titers. The intermediate and high doses of fluconazole reduced CSF fungal (P < .05) and CRAG (P < .001) titers earlier than low-dose fluconazole alone or in combination with flucytosine. Only the highest dose of fluconazole reduced brain edema after 7 days. In this model of cryptococcal meningitis, there was evidence of a dose response with fluconazole but no in vivo synergism with flucytosine.

Coupling of mutated Met variants to DNA repair via Abl and Rad51

Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Met, but not the wild-type form of the receptor, directly couple to the Abl tyrosine kinase and the Rad51 recombinase, two key signaling elements of homologous recombination-based DNA repair. Treatment of cells that express the mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant-dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a radiosensitizer together with the p53 inhibitor pifithrin-alpha by increasing cellular double-strand DNA break levels following exposure to ionizing radiation. Finally, we propose that in order to overcome a mutation-dependent resistance to SU11274, this aberrant molecular axis may alternatively be targeted with the Abl inhibitor, nilotinib.

Mandibular implant overdentures followed for over 10 years: patient compliance and prosthetic maintenance

PURPOSE: The mandibular implant overdenture is a popular treatment modality and is well documented in the literature. Follow-up studies with a long observation period are difficult to perform due to the increasing age of patients. The present data summarize a long-term clinical observation of patients with implant overdentures. MATERIALS AND METHODS: Between 1984 and 1997, edentulous patients were consecutively admitted for treatment with an implant overdenture. The dentures were connected to the implants by means of bars or ball anchors. Regular maintenance was provided with at least one or two scheduled visits per year. Recall attendance and reasons for dropout were analyzed based on the specific history of the patient. Denture maintenance service, relining, repair, and fabrication of new dentures were identified, and complications with the retention devices specified separately. RESULTS: In the time period from 1984 to 2008, 147 patients with a total of 314 implants had completed a follow-up period of >10 years. One hundred one patients were still available in 2008, while 46 patients were not reexamined for various reasons. Compliance was high, with a regular recall attendance of >90%. More than 80% of dentures remained in continuous service. Although major prosthetic maintenance was rather low in relation to the long observation period, visits to a dental hygienist and dentist resulted in an annual visit rate of 1.5 and 2.4, respectively. If new dentures became necessary, these were made in student courses, which increased the treatment time and number of appointments needed. Complications with the retention devices consisted mostly of the mounting of new female retainers, the repair of bars, and the changing of ball anchors. The average number of events and the rate of prosthetic service with ball anchors were significantly higher than those with bars. Twenty-two patients changed from ball anchors to bars; 9 patients switched from a clip bar to a rigid U-shaped bar. CONCLUSIONS: This long-term follow-up study demonstrates that implant overdentures are a favorable solution for edentulous patients with regular maintenance. In spite of specific circumstances in an aging population, it is possible to provide long-term care, resulting in a good prognosis and low risk for this treatment modality. For various reasons the dropout rate can be considerable in elderly patients and prosthetic service must be provided regularly.

Screening and treatment to prevent sequelae in women with Chlamydia trachomatis genital infection: how much do we know?

Background. An important question for chlamydia control programs is the extent to which finding and treating prevalent, asymptomatic Chlamydia trachomatis genital infection reduces reproductive sequelae in infected women. Methods. We reviewed the literature to critically evaluate evidence on the effect of chlamydia screening on development of sequelae in infected women. Results. Two randomized controlled trials of 1-time screening for chlamydial infection—in a Seattle-area health maintenance organization and a Danish school district—revealed that screening was associated with an ∼50% reduction in the incidence of pelvic inflammatory disease over the following year. However, both of these trials had methodological issues that may have affected the magnitude of observed screening benefits and might limit generalizability to other populations. A large, nonrandomized cohort of chlamydia screening among US Army recruits, although limited by lack of outpatient data, did not find a benefit of similar magnitude to the randomized trials. Methodological limitations restrict valid conclusions about individual benefits of screening using data from historical cohorts and ecological studies. We identified no trials directly evaluating the effect of chlamydia screening on subclinical tubal inflammation or damage, ectopic pregnancy, or tubal factor infertility and no studies addressing the effects of >1 round of screening, the optimal frequency of screening, or the benefits of screening for repeat infections. Conclusions. Additional studies of the effectiveness of chlamydia screening would be valuable; feasible study designs may depend on the degree to which screening programs are already established. In addition, better natural history data on the timing of tubal inflammation and damage after C. trachomatis infection and development of more accurate, noninvasive tools to assess chlamydial sequelae are essential to informing chlamydia control efforts.

The role of purinergic signaling in the liver and in transplantation: effects of extracellular nucleotides on hepatic graft vascular injury, rejection and metabolism

Extracellular nucleotides (e.g. ATP, UTP, ADP) are released by activated endothelium, leukocytes and platelets within the injured vasculature and bind specific cell-surface type-2 purinergic (P2) receptors. This process drives vascular inflammation and thrombosis within grafted organs. Importantly, there are also vascular ectonucleotidases i.e. ectoenzymes that hydrolyze extracellular nucleotides in the blood to generate nucleosides (viz. adenosine). Endothelial cell NTPDase1/CD39 has been shown to critically modulate levels of circulating nucleotides. This process tends to limit the activation of platelet and leukocyte expressed P2 receptors and also generates adenosine to reverse inflammatory events. This vascular protective CD39 activity is rapidly inhibited by oxidative reactions, such as is observed with liver ischemia reperfusion injury. In this review, we chiefly address the impact of these signaling cascades following liver transplantation. Interestingly, the hepatic vasculature, hepatocytes and all non-parenchymal cell types express several components co-ordinating the purinergic signaling response. With hepatic and vascular dysfunction, we note heightened P2- expression and alterations in ectonucleotidase expression and function that may predispose to progression of disease. In addition to documented impacts upon the vasculature during engraftment, extracellular nucleotides also have direct influences upon liver function and bile flow (both under physiological and pathological states). We have recently shown that alterations in purinergic signaling mediated by altered CD39 expression have major impacts upon hepatic metabolism, repair mechanisms, regeneration and associated immune responses. Future clinical applications in transplantation might involve new therapeutic modalities using soluble recombinant forms of CD39, altering expression of this ectonucleotidase by drugs and/or using small molecules to inhibit deleterious P2-mediated signaling while augmenting beneficial adenosine-mediated effects within the transplanted liver.

Postoperative hypoesthesia and pain: qualitative assessment after open and laparoscopic inguinal hernia repair

BACKGROUND: Chronic pain is an important outcome variable after inguinal hernia repair that is generally not assessed by objective methods. The aim of this study was to objectively investigate chronic pain and hypoesthesia after inguinal hernia repair using three types of operation: open suture, open mesh, and laparoscopic. METHODS: A total of 96 patients were included in the study with a median follow-up of 4.7 years. Open suture repair was performed in 40 patients (group A), open mesh repair in 20 patients (group B), and laparoscopic repair in 36 patients (group C). Hypoesthesia and pain were assessed using von Frey monofilaments. Quality of life was investigated with Short Form 36. RESULTS: Pain occurring at least once a week was found in 7 (17.5%) patients of group A, in 5 (25%) patients of group B, and in 6 (16.6%) patients of group C. Area and intensity of hyposensibility were increased significantly after open nonmesh and mesh repair compared to those after laparoscopy (p = 0.01). Hyposensibility in patients who had laparoscopic hernia repair was significantly associated with postoperative pain (p = 0.03). Type of postoperative pain was somatic in 19 (61%), neuropathic in 9 (29%), and visceral in 3 (10%) patients without significant differences between the three groups. CONCLUSIONS: The incidence of hypoesthesia in patients who had laparoscopic hernia repair is significantly lower than in those who had open hernia repair. Hypoesthesia after laparoscopic but not after open repair is significantly associated with postoperative pain. Von Frey monofilaments are important tools for the assessment of inguinal hypoesthesia and pain in patients who had inguinal hernia repair allowing quantitative and qualitative comparison between various surgical techniques.

Floods of the Upper Danube River and Its Tributaries and Their Impact on Urban Economies (c. 1350–1600): The Examples of the Towns of Krems/Stein and Wels (Austria)

This paper examines the impact of disastrous and ‘ordinary’ floods on human societies in what is now Austria. The focus is on urban areas and their neighbourhoods. Examining institutional sources such as accounts of the bridge masters, charters, statutes and official petitions, it can be shown that city communities were well acquainted with this permanent risk: in fact, an office was established for the restoration of bridges and the maintenance of water defences and large depots for timber and water pipes ensured that the reconstruction of bridges and the system of water supply could start immediately after the floods had subsided. Carpenters and similar groups gained 10 to 20 per cent of their income from the repair of bridges and other flood damage. The construction of houses in endangered zones was adapted in order to survive the worst case experiences. Thus, we may describe those communities living along the central European rivers as ‘cultures of flood management’. This special knowledge vanished, however, from the mid-nineteenth century onwards, when river regulations gave the people a false feeling of security.

Using state variables to model the response of tumour cells to radiation and heat: a novel multi-hit-repair approach

In order to overcome the limitations of the linear-quadratic model and include synergistic effects of heat and radiation, a novel radiobiological model is proposed. The model is based on a chain of cell populations which are characterized by the number of radiation induced damages (hits). Cells can shift downward along the chain by collecting hits and upward by a repair process. The repair process is governed by a repair probability which depends upon state variables used for a simplistic description of the impact of heat and radiation upon repair proteins. Based on the parameters used, populations up to 4-5 hits are relevant for the calculation of the survival. The model describes intuitively the mathematical behaviour of apoptotic and nonapoptotic cell death. Linear-quadratic-linear behaviour of the logarithmic cell survival, fractionation, and (with one exception) the dose rate dependencies are described correctly. The model covers the time gap dependence of the synergistic cell killing due to combined application of heat and radiation, but further validation of the proposed approach based on experimental data is needed. However, the model offers a work bench for testing different biological concepts of damage induction, repair, and statistical approaches for calculating the variables of state.