Post-treatment Concentration Research Articles

Male infertility: An audit of 70 cases in a single centre

ObjectivesTo audit the aetiology, treatment and predictors of outcome in infertile men who attended urology clinic of a private hospital in Lagos, Nigeria. Patients and MethodsA ten-year retrospective review of all male infertility cases managed in our facility. Data on the demography, presentations, clinical findings, aetiologies, investigations, treatments and outcomes of all patients seen over the study period were retrieved and analyzed. ResultsA total of 70 married men were managed for male factor infertility with mean age of 35.6 years. Forty-four (62.9%) had primary while 26 (37.1%) had secondary infertility. The commonest aetiology of male infertility was varicocoele in 53 (75.7%) followed by testicular atrophy in 9 (12.9%) patients. Varicocoelectomy was done in 52 (74.3%), vaso-vasostomy in 3 (4.3%) and medical therapy in 15 (21.4%) of the patients. There was significant difference between the mean pre- and post-treatment sperm concentration and motility. Following treatment, sixteen (22.9%) and 31 (44.3%) patients had improvement in their sperm concentration and motility respectively out of which 13 (18.6%) achieved pregnancy. The mean post-treatment sperm concentration and motility in those who achieved pregnancy were 35.7 millions/ml and 68.5%, respectively. In those who had varicocoelectomy, the sperm concentration and motility were increased in 34 (77.3%) and 23 (53.5%), reduced in 4 (9.1%) and 11 (25.6%) and unchanged in 6 (13.6%) and 9 (20.9%), respectively. All the patients who achieved pregnancy were those who had varicocoelectomy representing 25% of those patients who had varicocoelectomy. ConclusionVaricocoele represents the most common treatable cause of male factor infertility and treatment is accompanied with improved seminal fluid parameters as well pregnancy rate. Post-treatment sperm concentration and motility were the only factors that could predict the possibility of achieving pregnancy.

Bioavailability and biochemical effects of diclofenac sodium 0.1% ophthalmic solution in the domestic chicken (Gallus gallus domesticus).

To determine if topical ophthalmic diclofenac sodium 0.1% solution alters renal parameters in the domestic chicken, and to determine if the drug is detectable in plasma after topical ophthalmic administration. Thirty healthy domestic chickens. Over 7days, six birds were treated unilaterally with one drop of artificial tear solution (group 1), 12 birds were treated unilaterally (group 2) and 12 bilaterally (group 3) with diclofenac sodium 0.1% ophthalmic solution. Treatments were provided every 12h in all groups. Pre- and post-treatment plasma samples from all birds were evaluated for changes in albumin, total protein, and uric acid. Post-treatment samples of all birds, collected 15min post-administration, were analyzed by high-performance liquid chromatography with mass spectrometry for diclofenac sodium detection. A randomly selected renal sample from each group was submitted for histopathologic review. Changes in pre- and post-treatment plasma albumin were significant (P<0.05) in groups 2 and 3, but not for group 1. Pre- and post-treatment changes in total protein and uric acid were not significant for any group. Diclofenac sodium was not detectable (limit of detection=0.10ng/mL) in plasma samples from birds in group 1. Post-treatment concentration of diclofenac in group 3 was statistically greater than group 2 (P=0.0008). Histopathologic changes did not identify diclofenac-induced acute renal tubular necrosis. Ophthalmic diclofenac sodium 0.1% administered topically every 12h in one or both eyes for 7days is detectable in systemic circulation in the domestic chicken, but does not cause overt significant changes in plasma uric acid or total protein.

The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients

IntroductionWe aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL). Patients and methodsIL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis. ResultsThe IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5–38% versus 59%, 95% CI: 32–78%, respectively, p = 0.0004). ConclusionOur study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.

Naturally occurring acquired primary hypothyroidism in a cat due to lymphocytic thyroiditis

A five-year-old ovariohysterectomised female Bengal cat was presented for investigation of weight gain, despite dietary modification, and a dry, poor quality hair coat with diffuse scaling of the skin. Initial...

Do We Need the Chelation Therapy during Intensive Treatment of Acute Lymphoblastic Leukemia (ALL) in Children?

IntroductionChildren with ALL during the intensive chemotherapy receive multiple transfusions of packed red blood cell (pRBC) that may lead to iron overload. With each transfusion of pRBC the body is supplied with an about 200-250 mg of iron, which excessive accumulation in tissues, due to the lack of mechanism for its active excretion, may cause toxic organ damage.MethodsThe aim of the study was to evaluate the serum ferritin concentration in children with ALL, depending on the amount of transfused pRBCs and to determine the group of patients with a risk of iron overload. The study patients included 54 children with newly diagnosed ALL treated at the Department of Pediatrics, Hematology and Oncology between 2008 and 2011, according to the ALL IC BFM 2002 therapy protocol. Prior to initiation the treatment and during the intensive chemotherapy, serum ferritin concentration and the number of pRBC transfusions (ml/kg) were assessed separately for each of the three ALL risk groups-standard risk (SR), intermediate risk (IR) and high risk (HR).ResultsAfter the intensive chemotherapy the mean ± standard deviation (SD) of serum ferritin concentration in group HR (2770 ± 1175 ng/ml) was significantly higher compared to the median in group SR 844.4 ng/ml (452.5; 1316) (p = 0.0007) and the mean ± SD in group IR-1270 ± 673.1 ng/ml (p = 0.0040).Throughout the intensive chemotherapy children in HR group received the largest volume of pRBC transfusions (ml/kg) (156.2 ± 68.31 ml/kg). In IR and SR groups the amounts of transfused pRBCs were comparable, respectively 113.5 ± 39.86 and 113.8 ± 29.56 ml/kg.Significant positive correlation was found between the serum ferritin concentration and the total amount of transfused pRBCs (ml/kg) after intensive chemotherapy (p <0.0001).After intensive treatment the concentration of serum ferritin exceeding 1000 ng/ml, that has traditionally been used as a trigger for chelation therapy, was found in 30 of 54 patients, for a prevalence in the entire cohort of 55,6% including 6 out of 6 patients in HR group (100%), 14 out of 22 patients in IR group (63,6%) and 10 out of 24 patients in SR group (41,7%).The group of patients with post-treatment serum ferritin concentration exceeding 1000 ng/mL, received significantly more pRBC transfusions (ml/kg) (139.8 ± 44.92) than the groups with serum ferritin levels between 500-1000 ng/mL (103.6 ± 18.96) (p <0.001) and <500 ng/mL-83.52 ± 17.66 (p <0.05).ConclusionsThese observations indicate a need of monitoring the cumulative volumes of pRBC transfusions, especially in children with ALL HR group. There is a need of routine screening for iron overload using serum ferritin in patients during intensive chemotherapy, in order to identify patients with indications for early iron chelation therapy. This is particularly important because some of them will be candidates to a hematopoietic stem cell transplantation, whereas iron overload adversely affects outcome of transplantation. DisclosuresNo relevant conflicts of interest to declare.

Effect of HCl Post-Treatment on Morphology of Hydrothermally Prepared Titanate Nanomaterials with Optical Limiting Properties

The effect of post-treatment HCl concentration on titanate-titania transformation was investigated. Titanate was prepared by the alkaline hydrothermal treatment of TiO2, and then transformed to titania/titanate upon subsequent washing with 0.10-0.55 mol∙L-1 HCl. The titanate almost completely transformed to rutile when treated with HCl concentrations>0.78 mol∙L-1. Accompanying this phase transformation, the morphology of the sample changed from nanotubes to nanosheets and nanoparticles. This was related to the rate of phase transformation, which depended on the HCl concentration. Titanate became resolved into detached TiO6 octahedra during HCl treatment, and titanate-titania transformation occurred via rearrangement of the TiO6 octahedra. The phase transformation and morphological evolution were studied by Xray diffraction, and transmission and scanning electron microscopies. The linear and nonlinear optical properties of the products were investigated using ultraviolet-visible absorption spectroscopy and the open aperture Z-scan technique, respectively. The minimum transmittance at Z=0 and maximum optical limiting effect were obtained when the HCl concentration was 0.55 mol∙L-1. Different nonlinear optical effects were exhibited by different morphologies.

A critical appraisal of analyzing nasal provocation test results in allergen immunotherapy trials.

The statistical analysis of nasal provocation tests is very complex. We compared the conventional analysis with the maximally selected test statistics and the hierarchical ordered logistic model. We re-analyzed data from a trial with 112 patients suffering from grass pollen allergy. The patients had been randomized to receive either intralymphatic immunotherapy (ILIT) or subcutaneous immunotherapy (SCIT). The conventional analysis indicated that the logarithmized ratio between the pre- and the post-treatment threshold concentration was significantly lower for ILIT than for SCIT. The maximally selected test statistics was used to test different threshold symptom scores that would imply positive clinical symptoms at the given allergen concentration. A threshold score of 3 maximised the difference in improvement between the ILIT and the SCIT groups. The hierarchical ordered logistic model does not take threshold allergen concentrations as the basis for analysis, but the single scores measured at each concentration. This approach simultaneously considers the treatment effect (ILIT versus SCIT), the time effect (pre- versus post-treatment), and the dose effect (different allergen concentrations). The hierarchical ordered logistic model revealed that the clinical improvement was greater after ILIT than after SCIT. As the choice of method can affect the outcome, guidelines for analysis are highly needed.

A critical appraisal of analyzing nasal provocation test results in allergen immunotherapy trials

The statistical analysis of nasal provocation tests is very complex. We compared the conventional analysis with the maximally selected test statistics and the hierarchical ordered logistic model. We re-analyzed data from a trial with 112 patients suffering from grass pollen allergy. The patients had been randomized to receive either intralymphatic immunotherapy (ILIT) or subcutaneous immunotherapy (SCIT). The conventional analysis indicated that the logarithmized ratio between the pre- and the post-treatment threshold concentration was significantly lower for ILIT than for SCIT. The maximally selected test statistics was used to test different threshold symptom scores that would imply positive clinical symptoms at the given allergen concentration. A threshold score of 3 maximised the difference in improvement between the ILIT and the SCIT groups. The hierarchical ordered logistic model does not take threshold allergen concentrations as the basis for analysis, but the single scores measured at each concentration. This approach simultaneously considers the treatment effect (ILIT versus SCIT), the time effect (pre- versus post-treatment), and the dose effect (different allergen concentrations). The hierarchical ordered logistic model revealed that the clinical improvement was greater after ILIT than after SCIT. As the choice of method can affect the outcome, guidelines for analysis are highly needed.

Evaluation of CXCL8, CXCL10, CXCL11, CXCL12 and CXCL13 in serum and cerebrospinal fluid of patients with neuroborreliosis

PurposeKnowledge of the role of chemokines in the inflammation during neuroborreliosis (NB) is limited. We evaluated the pre- and post-treatment concentration of CXCL8, CXCL10, CXCL11, CXCL12, and CXCL13 in serum (s) and cerebrospinal fluid (csf) in patients with NB. ResultsThere was a statistically significant increase in pre-treatment s CXCL8, CXCL10, CXCL11, CXCL12, CXCL13 and csf CXCL8, CXCL11, CXCL12, CXCL13 in patients with early form of NB. CXCL8, CXCL11, CXCL12 and CXCL13 increase was the highest in csf. After treatment, a significant decrease in csf chemokine levels (except CXCL10) and s levels (except CXCL11) was observed. ConclusionsCXCL8, CXCL10, CXCL11, CXCL12, CXCL13 are involved in the pathomechanism of NB but their role is different in s and csf. CXCL13 seems to be a good biomarker for NB. In early NB, it may facilitate the diagnosis and monitoring of therapy. However tick-borne encephalitis needs to be excluded as it also increases chemokine concentration. Decrease in all examined chemokines in s and csf after treatment suggests that chemokines may be useful in monitoring response to NB therapy.

Analytical validation of a quantitative reverse transcriptase polymerase chain reaction assay for evaluation of T-cell targeted immunosuppressive therapy in the dog

Cyclosporine is an immunosuppressive agent that inhibits T-cell function by decreasing production of cytokines such as interleukin-2 (IL-2) and interferon-γ (IFN-γ). In dogs, there is currently no reliable analytical method for determining effective cyclosporine dosages in individual patients. Our laboratory has developed a quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) assay that measures IL-2 and IFN-γ gene expression, with the goal of quantifying immunosuppression in dogs treated with cyclosporine. This study focuses on analytical validation of our assay, and on the effects of sample storage conditions on cyclosporine-exposed samples. Heparinized whole blood collected from healthy adult dogs was exposed to a typical post-treatment blood concentration for cyclosporine (500ng/mL) for 1h, and then stored for 0, 24, and 48h at both room temperature and 4°C. The study was then repeated using a cyclosporine concentration of 75ng/mL, with sample storage for 0, 24, and 48h at 4°C. Cytokine gene expression was measured using RT-qPCR, and assay efficiency and inter- and intra-assay variability were determined. Storage for up to 24h at room temperature, and up to 48h at 4°C, did not significantly alter results compared to samples that were processed immediately. Validation studies showed our assay to be highly efficient and reproducible and robust enough to be feasible under standard practice submission conditions.

Changes in serum Interleukin-33 concentration before and after treatment with pegylated interferon alfa-2a plus ribavirin in patients with chronic hepatitis C genotype 1b infection

BackgroundIL-33 is a novel member of the IL-1 family, which has been shown to play an important role in T helper 2 (Th2)-associated immune responses. Recent studies have suggested a possible role for IL-33 in the pathogenesis of liver damage during acute and chronic hepatitis; furthermore, IL-33 may be involved in the development and progression of liver fibrosis.ObjectivesTo evaluate serum IL-33 levels in a group of patients with chronic hepatitis C (CHC) genotype 1b at enrolment and after a course of pegylated (PEG)-IFN plus ribavirin.Patients and Methods60 patients with chronic hepatitis C (CHC) and 65 healthy controls were examined and compared for serum IL-33 levels by ELISA. All CHC patients were submitted to liver biopsy either before starting antiviral treatment or during post-treatment follow up. We evaluated whether post-treatment IL-33 concentration was associated with histologic outcome as well as with virologic response to therapy.ResultsSerum IL-33 levels were significantly higher among CHC patients in comparison with healthy controls. IL-33 concentration was lower among patients with a METAVIR fibrosis score F1-F2, compared with those having a more advanced liver disease (METAVIR stage F3-F4). In addition, sustained virologic response (SVR) was associated with a significant drop in IL-33 levels, whereas no changes were found among relapsers and nonresponders. Analogously, patients experiencing liver histologic improvement after antiviral therapy had lower post-treatment IL-33 levels in comparison with baseline values. Contrarily, no variations were detected among subjects with worsened or stable histologic features.ConclusionsIL-33 may represent a new and easy-to-detect biomarker for the diagnosis of liver damage in CHC patients, as it appears to be modulated in parallel with biochemical and histologic parameters, such as ALT levels and liver fibrosis. Furthermore, considering that serum IL-33 concentration was significantly reduced following a successful course of antiviral treatment, this cytokine may also represent a sensitive indicator of SVR.

Correlation between salivary interleukin‐6 levels and early locoregional recurrence in patients with oral squamous cell carcinoma: Preliminary study

We have demonstrated that salivary interleukin-6 (IL-6) concentrations change during the treatment in patients with oral squamous cell carcinoma (OSCC). We sought to elucidate the correlations between salivary IL-6 concentration and early locoregional recurrence in OSCC. Stimulated saliva was collected before and after surgery from 27 consecutive patients with OSCC. Recurrence-free survival (RFS) curves were plotted using the Kaplan-Meier method. Of the 27 patients, 11 (41%) were diagnosed with locoregional recurrence within 24 months postsurgery. The median concentrations of IL-6 presurgery and postsurgery were 2.8 pg/mL and 2.1 pg/mL, respectively. The median postsurgery concentration of IL-6 was significantly higher in patients with than without locoregional recurrence (p = .02). Multivariate analysis revealed that postsurgery salivary IL-6 concentration was an independent risk factor for locoregional recurrence (p = .03; risk ratio, 0.14). Posttreatment concentration of salivary IL-6 may predict early locoregional recurrence in OSCC.

Effects of Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation on Serum Brain-Derived Neurotrophic Factor Levels in Patients with Depression

Objective: Brain-derived neurotrophic factor (BDNF) levels are decreased in individuals with depression and increase following antidepressant treatment. The objective of this study is to compare pre- and post-treatment serum BDNF levels in patients with drug-resistant major depressive disorder (MDD) who received either electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS). It is hypothesized that non-pharmacological treatments also increase serum BDNF levels. Methods: This was a prospective, single-blind study comparing pre- and post-treatment serum BDNF levels of 29 patients with drug-resistant MDD who received ECT or rTMS treatment. Serum BDNF levels were measured 1 week prior to and 1 week after treatment using the sandwich ELISA technique. Depression severity was measured 1 week before and 1 week after treatment using the Hamilton Depression Rating Scale. Two-sided normal distribution paired t-test analysis was used to compare pre- and post-treatment BDNF concentration and illness severity. Bivariate correlations using Pearson’s coefficient assessed the relationship between post-treatment BDNF levels and post-treatment depression severity. Results: There was no significant difference in serum BDNF levels before and after ECT, although concentrations tended to increase from a baseline mean of 9.95–12.29 ng/ml after treatment (p = 0.137). Treatment with rTMS did not significantly alter BDNF concentrations (p = 0.282). Depression severity significantly decreased following both ECT (p = 0.003) and rTMS (p < 0.001). Post-treatment BDNF concentration was not significantly correlated with post-treatment depression severity in patients who received either ECT (r = −0.133, p = 0.697) or rTMS (r = 0.374, p = 0.126). It is important to note that these results are based on the small number of patients included in this study. Conclusion: This study suggests that ECT and rTMS may not exert their clinical effects by altering serum BDNF levels in patients with drug-resistant MDD. Serum BDNF concentration may not be a biomarker of ECT or rTMS treatment response.

Supportive treatment with beta-erythropoietin in patients with lung cancer – Clinical data analysis of quality of life and effectiveness

Daganatos betegek körében gyakori szövődmény az anaemia, amelyet maga a betegség vagy az onkológiai kezelés okozhat. A vérszegénység rontja a betegek életminőségét, valamint a citotoxikus kezelés dóziscsökkentéséhez, illetve késleltetéséhez vezethet. A jelen retrospektív adatelemzés célja az volt, hogy elemezze 19 egymás után felvett, tüdőrákban szenvedő betegünk kemoterápia okozta anaemiájának béta-eritropoetinnel történő szupportációja során a betegek életminőségének és hemoglobinkoncentrációjának alakulását. A betegek átlagos, eritropoetinterápia előtti hemoglobinkoncentrációja 96,31±6,72 g/L volt (átlag±SD). Az anaemia szupportációjának befejezésekor az átlagos hemoglobinkoncentráció szignifikáns mértékben magasabb, 111,63±14,05 g/L volt (p&lt;0,05). A 19 beteg kezelése során 4 esetben volt szükség transzfúzióra. A betegek eritropoetin bevezetését megelőző átlagos életminőséget jellemző teljes pontszáma 22,89±5,67 volt, és szignifikáns mértékben javult a szupportáció mellett (27,84±6,14; p&lt;0,05). A kemoterápia okozta anaemiában szenvedő betegek életminőségének eritropoetin-béta-szupportáció mellett észlelt szignifikáns mértékű javulása megnyilvánult az alábbi részpontszámok szignifikáns mértékű javulásában: szédülést, tachycardiát, gyengeséget jellemző részpontszámok. A kis betegszám és az alkalmazott saját, csupán a betegdokumentáción alapuló kérdőív validáltságának hiánya természetesen korlátozza az adatok értékelhetőségét, az adatelemzés eredményei azonban felhívják a figyelmet az időben bevezetett erythropoeticus proteinszupportáció által biztosított jobb életminőség és alacsony transzfúziós szükséglet elérésének lehetőségére ebben az egyébként nagyon súlyos betegcsoportban. Orv. Hetil., 2010, 41, 1684–1688.

Pleiotropic effects of vitamin D in an early stage of chronic kidney disease-effect on insulin resistance.

Disturbances of carbohydrate metabolism are common in patients with chronic kidney disease (CKD). Possible pathogenetic mechanisms involve unresponsiveness of insulin receptor and/or a bland response of the beta cell at the stimulus of hyperglycaemia. It is known that vitamin D has an important role in the endocrine function of the pancreas, particularly in the insulin release process, and is one of the determinants of insulin resistance [1]. This metabolic complication may be implicated in the accelerated atherosclerotic process and is common in CKD. The aim of our study was to investigate the effect of vitamin D treatment on insulin resistance in patients with CKD stage 3. We included in our study 37 (25 men/12 women, age 51 ± 13 years old) non-diabetic patients with CKD stage 3 (eGFR 30–59 mL/min/1.73 m2 calculated with the Modification of Diet in Renal Disease formula). Patients with history of diabetes mellitus and previous therapy with vitamin D were excluded. The underlying kidney disease was obstructive nephropathy, secondary focal segmental glomerulosclerosis, membranous glomerulonephritis and unknown cause of CKD. In all patients, CKD–mineral and bone disorder (CKD–MBD) was established. All patients were treated at the beginning with dietary phosphorous restriction, phosphate-binding agents and calcium supplements. If intact parathyroid hormone (iPTH) values were persistently >70 pg/mL, administration of 1-alpha-hydroxyvitamin D3 in a single daily dose of 0.25 μg was initiated. Fasting glucose concentration, insulin levels, HbA1c, iPTH, Ca, P and insulin resistance evaluated by homeostasis model assessment index [HOMA index, calculated as: fasting glucose (mmol/L) × insulin (mU/mL) / 22.5] were measured before (T0) and 12 weeks after (T1) initiation of treatment. In all patients, an oral glucose tolerance test (OGTT) with an oral dose of 75 g of glucose was performed. No patient was under treatment with corticosteroids or erythropoietin for anaemia. Plasma levels of fasting glucose and insulin levels were comparable before (T0) and after (T1) treatment with vitamin D (Table 1). The HOMA index was statistically higher in time T0 than T1 indicating that insulin resistance was improved. Mean glucose OGTT levels were higher in T0. There was no statistical difference in calcium, phosphorous, HbA1c, pre- and post-treatment concentration, although the T1 calcium concentration was higher than T0. Table 1 Plasma levels of fasting glucose and insulin levels before and after treatment with vitamin D Vitamin D insufficiency is correlated with increased risk of all-cause and cardiovascular (CV) mortality in patients with stage 3 and 4 CKD [2]. Studies demonstrate a link between abnormalities in vitamin D metabolism and insulin resistance, a very common condition in patients with CKD. It is proven that insulin resistance is an independent predictor of morbidity and mortality for CV causes in non-diabetic patients with end-stage renal disease [3]. A few works have investigated the effect vitamin D has on insulin resistance in early stages of CKD. Our study has shown a beneficial effect of vitamin D supplementation in patients with CKD stage 3 on insulin resistance. The HOMA index and OGTT mean glucose plasma levels have significantly decreased after 1-alpha-hydroxyvitamin D3 treatment. Changes in PTH, a factor implicated in insulin resistance, were not significant during the study period and were not correlated with the amelioration of the HOMA index. Our conclusion was that vitamin D affected insulin metabolism directly and not through reduction of PTH in patients with stage 3 CKD. Insulin resistance is present in early stages of CKD and is associated with vitamin D metabolism. According to our data, treatment with vitamin D in patients with CKD stage 3 has a beneficial effect on insulin resistance assessed with the HOMA index. Of course, further randomized controlled large-scale studies are needed in order to assess long-term benefits in morbidity and mortality of those patients. Conflict of interest statement. None declared.

Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002–2008)

To determine whether changes in presurgical plasma lactate concentration (before and after initial fluid resuscitation and gastric decompression) were associated with short-term outcome for dogs with gastric dilatation-volvulus (GDV). Retrospective case series. 64 dogs. Medical records were reviewed, and signalment, history, resuscitative treatments, serial presurgical lactate concentrations, surgical findings, and short-term outcome were obtained for dogs with confirmed GDV. 36 of 40 (90%) dogs with an initial lactate concentration <or= 9.0 mmol/L survived, compared with only 13 of 24 (54%) dogs with a high initial lactate (HIL) concentration (> 9.0 mmol/L). Within HIL dogs, there was no difference in mean +/- SD initial lactate concentration between survivors and nonsurvivors (10.6 +/- 2.3 mmol/L vs 11.2 +/- 2.3 mmol/L, respectively); however, there were significant differences in post-treatment lactate concentration, absolute change in lactate concentration, and percentage change in lactate concentration following resuscitative treatment. By use of optimal cutoff values within HIL dogs, survival rates for dogs with final lactate concentration > 6.4 mmol/L (23%), absolute change in lactate concentration <or= 4 mmol/L (10%), or percentage change in lactate concentration <or= 42.5% (15%) were significantly lower than survival rates for dogs with a final lactate concentration <or= 6.4 mmol/L (91%), absolute change in lactate concentration > 4 mmol/L (86%), or percentage change in lactate concentration > 42.5% (100%). Calculating changes in plasma lactate concentration following initial treatment in dogs with GDV may assist in determining prognosis and identifying patients that require more aggressive treatment.

The effect of a single dose of topical 0.005% latanoprost and 2% dorzolamide/0.5% timolol combination on the blood‐aqueous barrier in dogs: a pilot study

To determine the effects of 0.005% latanoprost and 2% dorzolamide/0.5% timolol on the blood-aqueous barrier (BAB) in normal dogs. Eight mixed-breed and pure-breed dogs. Baseline anterior chamber fluorophotometry was performed on eight normal dogs. Sodium fluorescein was injected and the dogs were scanned 60-90 min post-injection. Seventy-two hours following the baseline scan, one eye received one drop of latanoprost. Fluorophotometry was repeated 4 h after drug administration. Following a washout period, the identical procedure was performed 4 h after the administration of dorzolamide/timolol. The degree of BAB breakdown was determined by comparing the concentrations of fluorescein within the anterior chamber before and after drug administration. BAB breakdown was expressed as a percentage increase in the post-treatment fluorescein concentration over the baseline concentration: %INC [Fl] = {([Fl](post)-[Fl](baseline))/[Fl](baseline)} x 100. The percentage increase in fluorescein concentration in the treated eye was compared to that in the nontreated eye using a paired t-test with significance set at P < or = 0.05. Following administration of latanoprost, the fluorescein in the treated eyes increased 49% (+/- 58%) from baseline compared to 10% (+/- 31%) in the untreated eyes (P = 0.016). Following administration of dorzolamide/timolol, the fluorescein concentration increased 38% (+/- 54%) compared to baseline vs. 24% (+/- 38%) in the untreated eyes (P = 0.22). The results of this study show that topical latanoprost may cause BAB disruption in normal dogs while topical dorzolamide/timolol may have no effect on the BAB in normal dogs.

Clinical significance of Epstein-Barr Virus DNA load detected pre- and post-radiotherapy in nasopharyngeal carcinoma patients

10558 Background: Plasma Epstein-Barr virus DNA (EBV DNA) load has been shown to be clinically useful in the detection, monitoring, and prognostication of nasopharyngeal carcinoma (NPC). However, the clinical significance of EBV DNA load detected at different time points has not been addressed to our knowledge. In this study, we investigated whether pre- and post-treatment plasma EBV DNA load have different prognostic implications in NPC patients who were treated with radiotherapy. Methods: Plasma samples from 69 patients with primary NPC were collected before and after radiation treatment, and subjected to a real-time quantitative polymerase-chain- reaction assay of EBV DNA load. The pre-treatment primary tumor volume (GTVnx) calculated through CT images and/or MRI were documented. All patients were scheduled to follow up. Results: The pre-treatment plasma EBV DNA concentration was significantly associated with primary tumor volume (Spearman correlation coefficient=0.614; P=0.000). With a cutoff value of 20,000 copies/ml and 0 copies/ml respectively for pre-treatment and post-treatment plasma EBV DNA copy number, patients with lower EBV DNA concentrations had statistically preferable progression-free survival,metastasis-free survival and overall survival compared with those with higher EBV DNA concentrations. Cox regression analysis demonstrated that both pre-treatment EBV DNA load (P=0.050;RR=3.95) and post-treatment EBV DNA load (P=0.001;RR=11.74) were risk factors for metastasis-free survival. When further integrating pre-treatment with post-treatment concentration of EBV DNA, it was demonstrated that whether EBV DNA concentration could be dropped to 0 after treatment dominate the prognostic effect for metastasis-free survival (P=0.000). Conclusions: Pre- and post-treatment plasma EBV DNA have different clinical significance. Pre-treatment plasma EBV DNA is a reliable molecular marker reflecting primary tumor volume. While the clearance of circulating plasma EBV DNA after treatment is a good predictive marker of freedom from distant metastasis. No significant financial relationships to disclose.

Synovial and plasma glucosamine concentrations in osteoarthritic patients following oral crystalline glucosamine sulphate at therapeutic dose

We investigated the synovial and plasma glucosamine concentrations in osteoarthritic patients following oral administration of crystalline glucosamine sulphate at the therapeutic dose of 1500mg once-a-day for 14 days. Twelve osteoarthritic patients (six males and six females) received 14 consecutive once-daily oral administrations of crystalline glucosamine sulphate soluble powder (1500mg), in an open fashion. Plasma and synovial fluid were collected simultaneously from the same patient, at baseline and, at steady state (3h after the last dose). Glucosamine was determined in plasma and synovial fluid by liquid chromatography-tandem mass spectrometry. Median endogenous glucosamine concentrations in plasma and synovial fluid were 52.0ng/ml (0.29microM) and 36.5ng/ml (0.21microM), respectively (P=0.001), and varied substantially among patients (41-121ng/ml and <10-67ng/ml, respectively). Three hours after the last dose, glucosamine concentrations resulted increased from baseline in all patients with median increases of 20.5 and 21.5 folds in plasma and synovial fluid, respectively, the difference being not statistically significant (P=0.11). In plasma, the median post-treatment value was 1282ng/ml (7.17microM) and ranged from 600 to 4061ng/ml (3.35-22.7microM). The median post-treatment synovial glucosamine concentration was 777ng/ml (4.34microM), i.e., significantly lower than in plasma (P=0.001), and ranged from 577 to 3248ng/ml (3.22-18.1microM). Plasma and synovial glucosamine concentrations were highly correlated and were in the 10microM range. Glucosamine is bioavailable both systemically and at the site of action (the joint) after oral administration of crystalline glucosamine sulphate in ostaeoarthritis patients. Steady state glucosamine concentrations in plasma and synovial fluid were correlated and in line with those effective in selected in vitro studies.

Semen quality before and after gonadotoxic treatment

The aim of this study was to analyse the semen quality of patients before and after gonadotoxic therapy. We evaluated semen quality in 314 patients over a 26 year period. The diagnostic categories were leukaemia (n = 13); lymphoma (n = 128); testicular cancer (n = 102); benign conditions (n = 13); and other malignant neoplasms (n = 58). The degree of azoospermia or oligozoospermia for each disease category was recorded. We then analysed the recovery in semen quality over time for each disease category. The mean patient age was 27.9 years (range 13-65 years). A total of 1115 post-treatment semen samples were analysed from 314 patients. There was a significant reduction in the post-treatment sperm concentration, sperm motility and semen volume compared with pre-treatment levels (P < 0.05) in the entire cohort. However, the sperm movement and motility grade remained unaffected. Patients with testicular carcinoma had the lowest pre-treatment sperm concentrations but also the lowest incidence of azoospermia after cancer treatment. Patients with lymphoma and leukaemia had the highest incidence of post-treatment azoospermia and oligospermia. Patients having the largest reductions in their sperm concentration after treatment required the longest recovery period for spermatogenesis. The diagnostic category was the only significant predictor of post-treatment azoospermia. Gonadotoxic treatment results in a significant reduction in sperm quality. The type of cancer or disease, and the pre-treatment sperm concentrations were found to be the most significant factors governing post-treatment semen quality and recovery of spermatogenesis. All categories of patients displayed varying degrees of azoospermia and oligozoospermia, and recovery of gonadal function from these states was not significant. This highlights the importance of ensuring sperm banking before treatment, including for patients with benign conditions. Several factors and associations are discussed further in order to give an insight into the pre- and post-gonadotoxic treatment effects.