Small Nerve Fiber Damage and Langerhans Cells in Type 1 and Type 2 Diabetes and LADA Measured by Corneal Confocal Microscopy

PurposeIncreased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and latent autoimmune diabetes of adults (LADA).MethodsPatients with T1DM (n = 25), T2DM (n = 36), or LADA (n = 23) and control subjects (n = 23) underwent detailed assessment of peripheral neuropathy and corneal confocal microscopy. Corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and total, immature and mature LC densities were quantified.ResultsLower CNFD (P < 0.001), CNBD (P < 0.0001), and CNFL (P < 0.0001) and higher LC density (P = 0.03) were detected in patients with T1DM, T2DM, and LADA compared to controls. CNBD was inversely correlated with mature (r = –0.5; P = 0.008), immature (r = –0.4; P = 0.02) and total (r = –0.5; P = 0.01) LC density, and CNFL was inversely correlated with immature LC density (r = –0.4; P = 0.03) in patients with T1DM but not in patients with T2DM and LADA.ConclusionsThis study shows significant corneal nerve loss and an increase in LC density in patients with T1DM, T2DM, and LADA. Furthermore, increased LC density correlated with corneal nerve loss in patients with T1DM.     

PDE5 inhibition against acute renal ischemia reperfusion injury in rats: does vardenafil offer protection?

Purpose

To evaluate the effect of vardenafil on renal function after renal ischemia–reperfusion (IR) injury (IRI) in a rat model.

Materials and methods

Seventy-one Wistar rats were divided into 7 groups including (1) a vehicle-treated group, (2) a vehicle pretreated-IR group, (3–6) vardenafil pretreated-IR groups in doses of 0.02, 0.2, 2 and 20 μg/kg, respectively, (7) a group of IR followed by treatment with 2 μg/kg of vardenafil. Vardenafil or vehicle solution was administered one hour before unilateral nephrectomy and the induction of 45 min of ischemia on the contralateral kidney by clamping of renal pedicle. Four hours of reperfusion were allowed after renal ischemia. Studied parameters were serum creatinine, fractional excretion of sodium (FENa), and histological evaluation of renal specimens. In addition, renal tissue cGMP levels, ERK1/2 phosphorylation as well as renal function by renal scintigraphy were also evaluated.

Results

Administration of vardenafil before the induction of ischemia resulted in a significant reduction in creatinine and FENa levels as well as in less histological lesions observed in treated kidneys in comparison with the vehicle-treated group. The underlying mechanism of cytoprotection was cGMP depended and involved the phosphorylation of ERK proteins. Renal scintigraphy confirmed that PDE5 inhibition attenuates renal IRI.

Conclusions

Vardenafil attenuates renal IRI. Based on similar results from relevant studies on other PDE-5 inhibitors in renal and cardiac IRI, it can be assumed that all PDE-5 inhibitors share a common mechanism of cytoprotection.     

Prognostic scoring system for peripheral nerve repair in the upper extremity

So far, predictive models with individualized estimates of prognosis for patients with peripheral nerve injuries are lacking. Our group has previously shown the prognostic value of a standardized scoring system by examining the functional outcome after acute, sharp complete laceration and repair of median and/or ulnar nerves at various levels in the forearm. In the present study, we further explore the potential mathematical model in order to devise an effective prognostic scoring system. We retrospectively collected medical record data of 73 cases with a peripheral nerve injury in the upper extremity in order to estimate which patients would return to work, and what time was necessary to return to the pre‐injury work. Postoperative assessment followed the protocol described by Rosén and Lundborg. We found that return to pre‐injury work can be predicted with high sensitivity (100%) and specificity (95%) using the total numerical score of the Rosén and Lundborg protocol at the third follow‐up interval (TS3) as well as the difference between the TS3 and the total score at second follow‐up interval (TS2). In addition, the factors age and type of injured nerve (median, ulnar, or combined) can determine the time of return to work based on a mathematical model. This prognostic protocol can be a useful tool to provide information about the functional and social prospects of the patients with these types of injuries. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.     

Biocompatibility Study Based on Differential Sequestration Kinetics of CD14+CD16+ Blood Monocyte Subsets with Different Dialyzers

The immune defect in hemodialysis (HD) patients is associated with a monocyte dysfunction, including an increase in the production of proinflammatory cytokines. Blood membrane contact leads to an increase in cellular activation and sequestration into the capillary bed of the lung. The influence of the sequestration on the number of mature monocytes was studied by analyzing the fate of monocytes, particularly, the CD14+CD16+ subpopulation, during HD treatment.

In thirty stable HD patients, the distinct cell populations were determined by differential blood counts and flow cytometry. Patients with diabetes or systemic vasculitis, those showing evidence of infectious complications or malignancy, or those taking immunosuppressive medications were excluded from the study. Cells from this study population were analyzed before the start, 30 min thereafter, and at the end of HD treatment, each time using a different dialyzer: hemophan, methylmethacrylate (PMMA), triacetate membrane, cuprophane/vitamin E, acrylonitrile, and sodium methallylsulfonate polymer (AN69).

The CD14+CD16+ subset decreased at 30 min and remained suppressed for the course of dialysis. To examine whether currently used biocompatible membranes differ in their effect on the sequestration of monocyte subpopulations, temporal monocytic changes were comparatively analyzed during HD with a different dialyzer. The drop in the first 30 min until the end of HD treatment was significant (p<0.05), very uniform, and sharp in all patients, and was independent upon membrane type.

The CD14+CD16+ monocyte subpopulation showed increased and longer margination from the blood circulation during HD. Given the fact that CD14+CD16+ monocytes represent a sensitive marker for inflammation or cellular activation, the depletion of these cells may offer an easily accessible parameter that is more sensitive than complement activation for biocompatibility studies on forthcoming, improved dialyzer membranes.     

Oxidative stress in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and the significant role of vitamin C and E supplementation

Purpose

Chronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol.

Methods

Plasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals.

Results

All studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation.

Conclusions

The oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients.     

Evidence for treatment of muscular vein thrombosis in orthopaedic patients

Background

Does below-knee symptomatic muscular (gastrocnemius or soleus) vein thrombosis (MVT) warrant investigation and treatment in post-operative orthopaedic patients? We performed a literature search and evaluated the evidence looking for guidance regarding this question.

Materials and methods

We performed a literature search with the use of PubMed, Medline and Google Scholar from 1950 to September 2011. Search terms included “muscular vein thrombosis” (MVT) and “isolated gastrocnemius or soleus vein thrombosis” (IGSVT). We reviewed the eight level II studies relevant to our search, only one of which was in a specific orthopaedic population.

Results

Studies looking at the rates of progression of isolated MVT have shown conflicting results. There is also a lack of consensus between studies that compare progression amongst groups with or without anticoagulant treatment. The majority of the studies do not distinguish between medical, surgical or orthopaedic patients.

Conclusions

We cannot confidently recommend commencement of anticoagulation treatment upon identification of MVT in post-operative orthopaedic patients. We can only suggest that, once MVT is diagnosed, the patient should undergo serial ultrasound scan (USS) duplex scans, and if propagation is identified, then treatment may be deemed beneficial.Level of evidence: III (review of non-randomized controlled cohort/follow-up studies).     

Giant extra gastrointestinal stromal tumor of lesser omentum obscuring the diagnosis of a choloperitoneum

INTRODUCTIONHerein we present an extremely rare case of a giant extra gastrointestinal stromal tumor (EGIST) of the lesser omentum obscuring the diagnosis of a choloperitoneum.PRESENTATION OF CASEA 79 years old female was admitted to our hospital with symptoms of vomiting and epigastric pain. Abdominal computer tomography revealed a sizable formation that was diagnosed as a tumor of the pancreas. In laparotomy, a choloperitoneum was diagnosed as the cause of patient's symptoms. A tumor adherent firmly to the lesser curvature of stomach was also discovered. Cholecystectomy and subtotal gastrectomy were performed. Histologically, the tumor was diagnosed as a EGIST of the lesser omentum. The patient did not receive any adjuvant therapy and after two years of follow up she is without any recurrence.DISCUSSIONOmental EGISTs may remain clinically silent despite the large tumor's size. It is difficult to differentiate a EGIST in the lesser omentum from a GIST of the lesser curvature of the stomach, despite the use of advanced radiological imaging techniques. Our case of a giant EGIST of lesser omentum obscuring the diagnosis of acute choloperitoneum is the only one reported in literature.CONCLUSIONEGISTs that arise from the omentum are very rare and complete surgical resection is the only effective treatment approach. Adjuvant therapy following resection of localized disease has become standard of care in high risk cases.