Biochemical and histopathological evaluation of histamine receptors (H1R,H2R,H3R and H4R)-agonist in rabbits

The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R–H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 μg/kg × b.i.d.) and H1R–H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[?]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 μg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R–H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies.     

Immunological,biochemical and histopathological evaluation of histamine receptors (H1R,H2R,H3R and H4R)-antagonist in rabbit experimental model: A short term study

The present study was designed to delineate the immuno- and hepatotoxicological roles of HRs-antagonists in vivo which is elementary in existing literature. The cohort comprised of two experimental studies. Experimental study 1 was designed for immunological investigations and consisted of seven groups and immunized with intravenous injection of SRBC at day 3 containing six rabbits each. Experimental study 2 was designed to assess the functional status of liver and comprised of seven groups containing five rabbits each. In both experimental studies group-I received sterile distilled water intramuscularly, and group II–VI received subcutaneous histamine, pheniramine (H1R-antagonist), ranitidine (H2R-antagonist), iodophenpropit (H3R-antagonist) and JNJ7777120 (H4R-antagonist), respectively while group-VII received DMSO intramuscularly. ELISA was used to assess the immunological investigations. The SRBC-specific immunoglobulins (Igs), IgM and IgG were significantly increased (p < 0.05). Hepatotoxicity due to same histamine and HRs-antagonists were demonstrated by biochemical and histopathological methods. Rabbits in group II–VI had significantly (p < 0.05) elevated levels of serum enzymes (ALT, AST, ALP) and bilirubin. Histopathological examination showed maintained hepatic lobular architecture in histamine and DMSO-treated groups a kin to control. Notable findings in other groups included increased binuclearity in H1R, trinuclearity in H2R, oxyphilic clusters of hepatocytes in H3R and moderate centrilobular necrosis in H3R and H4R-antagonist-treated groups without obvious inflammatory cell infiltration and Kupffer cell prominence. It is concluded that HRs-antagonist play immune suppressive role through H1R, H2R and H4R while immune enhancing role through H3R. In addition, HRs-antagonists appear moderately hepatotoxic in terms of altered serum enzyme levels and non-inflammatory hepatocellular damage.     

Caspase-cleaved fragments of cytokeratin-18 as a marker of inflammatory activity in chronic hepatitis B virus infection

BackgroundThe differential diagnosis between inactive carrier and active hepatitis is important in patients with chronic hepatitis B (CHB) virus infection. Serum cytokeratin (CK)-18 fragments (M30-antigen) are proposed as biomarkers of apoptosis.ObjectivesWe investigated whether serum M30-antigen levels might help to characterize the various phases of CHB and predict the state of significant inflammation in patients with CHB.Study designA total of 339 CHB patients who underwent liver biopsy, were included. Serum M30-antigen levels were compared between inactive carriers (n = 21), patients with HBeAg-negative hepatitis (n = 95), HBeAg-positive hepatitis (n = 141) and liver cirrhosis (n = 82).ResultsSerum M30-antigen levels were correlated significantly not only with AST (r = 0.544, p < 0.001) and ALT (r = 0.315, p < 0.001) and but also inflammatory grading score on liver biopsy (r = 0.240, p < 0.001). Serum M30-antigen level in HBeAg-negative CHB was significantly higher than that of inactive HBV carrier (399.78 U/L vs 148.90 U/L, p < 0.001). Multivariate analysis showed that AST (p < 0.001), albumin (p = 0.009) and M30-antigen (p = 0.020) were the independent predictors of significant inflammation. Combined serum M30-antigen level (>344 U/L) and AST (>78 IU/L) measurement provided the most accurate identification of significant inflammation, showing 38.2% sensitivity, 96.1% specificity, 91.0% positive predictive value and 56.1% negative predictive value.ConclusionsSerum M30-antigen can be a predictive marker for distinguishing between inactive carrier and HBeAg-negative CHB. Serum M30 levels are associated with the presence of significant inflammation, especially in patients with normal or minimally elevated ALT in CHB patients.     

Recruiting colorectal cancer survivors to a surveillance study: Barriers and successful strategies

BackgroundColorectal cancer (CRC) survival rates are increasing. Effective strategies to recruit CRC survivors to surveillance studies are needed.ObjectiveWe analyzed the barriers encountered while recruiting CRC survivors to a study assessing their surveillance care experiences.MethodsThe study included three phases: (I) focus groups/key informant interviews; (II) cognitive interviews; and (III) a statewide population-based telephone survey.ParticipantsIn Phases I–II, clinic-based data and cancer center registries were used to identify CRC survivors who had received CRC resection within the past 18 months. In Phase III, survivors who had received CRC resection within the past two years were identified via a statewide, population-based cancer registry.ResultsIn Phase I, 16 survivors participated in focus groups at two National Cancer Center-affiliated sites (response rate = 29.6%). Eighteen additional survivors participated in individual interviews (response rate = 50%). In Phase II, 11 survivors participated in cognitive interviews (response rate = 81.8%). In Phase III, 150 survivors participated in the statewide survey (response rate = 62.2%).ConclusionsGroup-based/in-person recruitment efforts were unsuccessful due to scheduling barriers, lack of transportation, and remaining discomfort from previous resection surgery. Telephone-based data collection strategies produced higher response rates.Practice implicationsTo enhance CRC surveillance research, future studies could incorporate CRC survivor-centered recruitment strategies.     

Comparison of second-look arthroscopic findings and clinical results according to the amount of preserved remnant in anterior cruciate ligament reconstruction

BackgroundAlthough ACL reconstruction is prevalent, the most effective method for ACL reconstruction still remains controversial. The purpose of this study was to evaluate the effect of the preserved remnant in ACL reconstruction on graft morphology at second-look arthroscopy and clinical outcomes.Methods66 consecutive patients who underwent a second-look arthroscopy after a remnant-preserving ACL reconstruction were enrolled. The patients were divided into two groups according to whether the remnant ACL fibers could be preserved by over 50% (Group I) or not (Group II). The Lysholm score, IKDC subjective score, Tegner activity score, pivot-shift test, and KT-2000 arthrometric findings were evaluated preoperatively and just prior to the second-look arthroscopy to assess clinical outcomes. At second-look arthroscopy, graft morphology was evaluated using hypertrophy rate and synovialization.ResultsAt second-look arthroscopy, the hypertrophy rate of Group I (42.1%) was higher than Group II (25.1%), which was statistically significant (p = 0.002). In graft synovialization, there was a statistically significant difference between the two groups (p < 0.001). The IKDC subjective score improved from 42.9, 43.1 to 77.8, 75.0 for Group I and Group II, respectively (p = 0.025). For the Lysholm score, Group I and Group II improved from 55.4 and 55.7 to 87.8 and 84.9 (p = 0.031). There was also a significant difference between the pivot shift tests between the groups (p = 0.039). Other clinical tests showed no statistically significant differences.ConclusionPreserving the remnant ACL tissue during ACL reconstruction could have a positive effect on graft hypertrophy, synovialization and clinical outcomes.Level of evidenceIII, retrospective comparative study.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.     

Toxicopathological studies on the effects of aflatoxin B1, ochratoxin A and their interaction in New Zealand White rabbits

New Zealand White rabbits, divided into 4 groups were fed with feed containing aflatoxin B₁ (AFB₁) @ 0.5 ppm (group I), ochratoxin A (OA) @ 1 ppm (group II), AFB₁ and OA @ 0.5 ppm and 1 ppm, respectively (group III) and standard feed (group IV) for 60 days. Mortality and decrease in body weight were highest in the interaction group. Superoxide dismutase, catalase and malondialdehyde levels were increased in all the toxin fed groups with maximum elevation in group III. Significant decrease in the antibody titre to sRBC was observed in groups I and II. Significant reduction of HI and CMI responses was observed in group III. Grossly, liver was the most affected organ in AFB₁ treated animals. Microscopically, vacuolar degeneration of hepatocytes, bile duct epithelial hyperplasia and hypertrophy and peribiliary fibrosis were consistently observed. Ultrastructurally, hepatocytes revealed varying degrees of degeneration, swollen endoplasmic reticulum and pleomorphism of mitochondria. OA produced significant nephrotoxicity with the pale, soft and enlarged kidneys showing discoloured foci over the surface. Microscopically, kidneys revealed degeneration of the proximal convoluted tubules and the testes were atrophic. Ultrastructurally, disruption of the mitochondrial membrane and swelling of the endoplasmic reticulum were observed. In group III, gross and histopathological changes were observed both in liver and kidneys and were of greater severity as compared to those of groups I and II. Ultrastructurally, hepatocytes revealed nuclear distortion, marginated heterochromatin, chromatolysis, electron opaque mitochondria with vacuolations and disarray of cristae and loss of cytoplasmic organelles. The results suggested an additive interaction of AFB₁ and OA in rabbits.     

Prevalence and risk factors for endogenous fungal endophthalmitis in adult patients with candidemia at a tertiary care hospital in the Republic of Korea over 13 years

BackgroundEndogenous fungal endophthalmitis (EFE) is a critical complication of candidemia. We conducted a study to investigate the prevalence and risk factors for EFE.MethodsAdult candidemia patients ≥ 19 years who underwent an ophthalmological examination at a tertiary care hospital in the Republic of Korea from 2006 to 2018 were enrolled.ResultsThere was a total of 152 adult candidemia patients analyzed. EFE was found in 29 patients (19.1%). Patients were categorized into two groups (Non-endophthalmitis [NE] and endophthalmitis [E]). Between the two groups, there was no significant difference in terms of age, sex, and underlying comorbidities. However, there were more Candida albicans candidemia, abnormal alanine aminotransferase (ALT) at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours after onset of candidemia symptoms and blood culture sample (AOCS), and candidemia clearance ≥ 5 days after initiation of antifungal treatment (AIAT) in the E group. A predictive model for the E was created, which had an area of 0.811 under the receiver operating characteristics curve. In a multivariate logistic regression analysis, C. albicans candidemia, ALT at the time of candidemia diagnosis, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT were significantly associated with EFE.ConclusionEFE occurred in 19% of adult patients with candidemia. Adult candidemia patients with C. albicans candidemia, abnormal ALT, receipt of antifungal treatment ≥ 48 hours AOCS, and candidemia clearance ≥ 5 days AIAT need to be closely monitored for the possibility of EFE.     

Attenuation of cyclophosphamide-induced neurotoxicity in rat by yellow dye extract from root of Brimstone tree (Morinda lucida)

Cyclophosphamide is an anticancer and immunosuppressant drug that induces reactive oxygen species (ROS) production, so causing malondialdehyde (MDA) production, which is toxic to cells. This study therefore sought to assess the antioxidant and the protective effect of dietary inclusion (0.5 and 1.0%) of yellow dye from root of Brimstone tree (used to enhance the sensory quality of foods and in folk medicine) on cyclophosphamide-induced oxidative stress in brain. Wistar strain albino rats were placed on diet containing 0.5 and 1.0% yellow dye preparation from root of Brimstone tree for 14 days. Intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 h before the termination of the experiment caused a significant (P < 0.05) increase in the brain malondialdehyde (MDA) content (147.2%) and serum activities of aspartate aminotransferase (AST) (21.7 UI/l), alanine amino-transferase (ALT) (29.6 UI/l), alkaline phosphatase (43.8UI/l) and total bilirubin (1.7 mg/dl). However, there was a significant decrease (P < 0.05) in the MDA of content of the brain and serum enzyme activities, in those rats fed diet containing the yellow dye in a dose dependent manner. The inhibition of oxidative stress in brain and serum enzymes and metabolites by the dye could be attributed to its high total phenol content and antioxidant activity as typified by its reducing power, free-radical scavenging ability, Fe(II) chelating ability and inhibition of lipid peroxidation. Therefore, dietary inclusion of the yellow dye from root of Brimstone tree could prevent cyclophosphamide-induced oxidative stress in brain and the associated toxicity to the liver.     

A plant cell-expressed recombinant anti-TNF fusion protein is biologically active in the gut and alleviates immune-mediated hepatitis and colitis

The orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) (n = 6) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human antibody IgG1 domain.AimTo evaluate the immune modulatory effect of the oral administration of plant cells expressing PRX-106.MethodsMice treated with Concanavalin A (ConA) to induce immune hepatitis was orally treated with cells expressing PRX-106 containing 0.5 or 5 μg PRX 106. In the colitis model, TNBS-colitis was induced in mice followed by the oral administration of plant cells expressing PRX-106. The immune modulatory effect was determined through follow-up to assess the clinical effect, histology, and serum cytokine levels and by FACS analysis for lymphocyte subsets.ResultsThe oral administration of BY-2 cells expressing PRX-106 alleviated immune-mediated liver injury. Serum AST and ALT levels decreased and were comparable to those of mice that had received high-dose steroids. The beneficial effect was also observed as a marked decrease in hepatic necrosis. In the colitis model, the oral administration of BY-2 plant cells expressing PRX-106 alleviated weight loss associated with immune-mediated colitis and improved bowel histology. A reduction in I-IkB-alpha phosphorylation in treated mice was also observed. These effects were associated with a significant alteration in the distribution of CD4 + CD25 + FOXP3+ cells.ConclusionsPlant cells expressing recombinant anti-TNF fusion protein show biological activity when orally administered, exerting an immune modulatory effect through the alleviation of immune-mediated hepatitis and immune-mediated colitis.     

Détermination de la testostérone biodisponible chez la femme adulte par chromatographie en phase gazeuse–spectrométrie de masse avec dilution isotopique (ID-GCMS). Comparaison avec la méthode de routine à la testostérone tritiée

Accurate measurement of androgens is particularly problematic in women who have lower plasma concentrations of total T (T tot) and Bioavailable Testosterone (T Bio) respectively 10-fold and 100-fold lower than men. Moreover, women taking oral estrogens have higher levels of T tot because of the increase in sex hormone binding globulin (SHBG) levels. It results that Bioavailable or Free T is decreased and this is the best parameter to measure because the only non-SHBG bound Testosterone (Free T + albumin-bound T) diffuses easily from circulation to tissues and is available for target cells. Direct RIA using the analog tracer technique has little to recommend it, salivary assays are highly variable and those that directly measure Free T in the dialysate are not commercially available and are labor intensive. The objective of this study is to evaluate a sensitive method for the measurement of the low total and bioavailable Testosterone levels in Female Androgen Insufficiency (FAI) other than menopause with androgen values at or below the lowest quartile of the reference range for reproductive age women (20–40 years) in conjunction with the presence of clinical symptoms and adequate estrogen status. An application of the most specific technique of steroid analysis, the Stable Isotope Dilution/Gas Chromatography-Mass Spectrometry (ID-GCMS) to validate Bioavailable Testosterone assays has been lacking to date. Therefore, we compare two experimental approaches (indirect and direct) to determine T Bio: 1) the indirect determination by measurement of the percentage of non-SHBG bound steroid after incubating at 37 °C the serum samples with freshly purified tracer dose of tritiated testosterone [³H]T and precipitation with saturated ammonium sulfate solution (final: 50% saturation); to obtain the concentration of T Bio: T Bio ³H E170 (III) or T Bio ³H MS (IV), we multiplied this percentage by total Testosterone: T tot E170 (I) or T tot MS (II) determined respectively by the ECLIA method on Modular E-170 Roche and by ID-GCMS; 2) the direct measurement by ID-GCMS of the T Bio MS (V) concentration in the supernatant after the ammonium sulfate precipitation step. Sensitivity of ID-GCMS (with a signal to noise of 3:1) is 2 pg injected of derivatized Testosterone. For the ID-GCMS methods II and V, the overall method recoveries are 82% and 92% respectively, CV within-assay are 3.9% (126 pg/ml) and 6.2% (13.8 pg/ml), CV between-assays are 4.3% (126 pg/ml) and 17.3% (15.4 pg/ml). For the T Bio ³H methods III and IV, within- and between-run CV are 4.5% at 2.8 pg/ml and 3.7% at 58.4 pg/ml respectively. Our data show highly significant (P < 0.001) correlation coefficients for Ttot: I with II (r = 0.88) and between indirect (III or IV) and direct techniques (V) for T Bio : III with V (r = 0.85) and IV with V (r = 0.90). This demonstrates the analytical validity of the indirect approach if we consider the direct technique by ID-GCMS as a reference measurement procedure. The method T tot E170 (I) has acceptable performance (between-run CV = 20% at 120 pg/ml) for routine investigations but T tot MS (II) is required at lower levels (between-run CV = 4.3% at 126 pg/ml) or whenever maximal reliability is requested. The validity of the T Bio ³H results depends on the validity of the total T results on which they are calculated. Despite this limitation, if we use the criteria of maintaining imprecision within- and between-run (CV) < 5% et < 10% respectively at or below (T Bio < 6 pg/ml) the lowest quartile of the reference range for reproductive age women (20–40 years), T Bio ³H methods III and IV are the only adequate techniques for routine use although the direct ID-GCMS method V has high but insufficient sensitivity.     

Toxicity of methimazole on femoral bone in suckling rats: Alleviation by selenium

AimsSelenium has a pharmacological properties and it is well considered as an antioxidant. The present study investigated the potential ability of selenium, used as a nutritional supplement, to alleviate bone impairments in suckling rats whose mothers were treated with methimazole, an antithyroid drug.Main methodsFemale Wistar rats were randomly divided into four groups of six each: group I served as control which received standard diet; group II were rendered hypothyroid by administration of methimazole (250 mg L^?1 in their drinking water); group III received both methimazole (250 mg L^?1 in their drinking water) and selenium (0.5 mg kg^?1 of diet); group IV received 0.5 Na₂SeO₃ mg kg^?1 of diet. Treatments were started from the 14th day of pregnancy until day 14 after delivery.Key findingsMethimazole treatment decreased femur length and weight in 14-day-old rats, when compared to controls. Femur antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high femur malondialdehyde levels. Methimazole also caused a significant decrease in calcium and phosphorus levels in bone. Yet, in plasma and urine, they increased and decreased inversely. Besides, plasma total tartrate-resistant acid phosphatase was enhanced, while total alkaline phosphatase was reduced. Co-administration of selenium through diet improved the biochemical parameters cited above. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat femur was alleviated by Se treatment.SignificanceThe present study suggests that selenium is an important protective element that may be used as a dietary supplement protecting against bone impairments.     

Early versus late treatment of spinal cord compression with long-term intrathecal enzyme replacement therapy in canine mucopolysaccharidosis type I

Enzyme replacement therapy (ERT) with intravenous recombinant human alpha-l-iduronidase (IV rhIDU) is a treatment for patients with mucopolysaccharidosis I (MPS I). Spinal cord compression develops in MPS I patients due in part to dural and leptomeningeal thickening from accumulated glycosaminoglycans (GAG). We tested long-term and every 3-month intrathecal (IT) and weekly IV rhIDU in MPS I dogs age 12–15 months (Adult) and MPS I pups age 2–23 days (Early) to determine whether spinal cord compression could be reversed, stabilized, or prevented. Five treatment groups of MPS I dogs were evaluated (n = 4 per group): IT + IV Adult, IV Adult, IT + IV Early, 0.58 mg/kg IV Early and 1.57 mg/kg IV Early. IT + IV rhIDU (Adult and Early) led to very high iduronidase levels in cervical, thoracic, and lumber spinal meninges (3600–29,000% of normal), while IV rhIDU alone (Adult and Early) led to levels that were 8.2–176% of normal. GAG storage was significantly reduced from untreated levels in spinal meninges of IT + IV Early (p < .001), IT + IV Adult (p = .001), 0.58 mg/kg IV Early (p = .002) and 1.57 mg/kg IV Early (p < .001) treatment groups. Treatment of dogs shortly after birth with IT + IV rhIDU (IT + IV Early) led to normal to near-normal GAG levels in the meninges and histologic absence of storage vacuoles. Lysosomal storage was reduced in spinal anterior horn cells in 1.57 mg/kg IV Early and IT + IV Early animals. All dogs in IT + IV Adult and IV Adult groups had compression of their spinal cord at 12–15 months of age determined by magnetic resonance imaging and was due to protrusion of spinal disks into the canal. Cord compression developed in 3 of 4 dogs in the 0.58 mg/kg IV Early group; 2 of 3 dogs in the IT + IV Early group; and 0 of 4 dogs in the 1.57 mg/kg IV Early group by 12–18 months of age. IT + IV rhIDU was more effective than IV rhIDU alone for treatment of meningeal storage, and it prevented meningeal GAG accumulation when begun early. High-dose IV rhIDU from birth (1.57 mg/kg weekly) appeared to prevent cord compression due to protrusion of spinal disks.     

Crucial parameter of the outcome in Crimean Congo hemorrhagic fever: Viral load

BackgroundCrimean Congo hemorrhagic fever (CCHF) is a fatal disease with a mortality rate of 5–30%. CCHF can be asymptomatic or it may progress with bleeding and cause mortality.ObjectivesTo evaluate relation of viral load with mortality, clinical and laboratory findings in CCHF.Study designA total of 126 CCHF patients were included. Serum samples obtained from all patients on admission for measurement of viral load.ResultsIn our study, mortality rate was 11.1%. The most important prognostic factor was viral load. Mean viral load was 8.3 × 10⁷ copy/ml and 4.6 × 10⁹ copy/ml in survived and dead patients, respectively (p < 0.005). Probability of survival is found to be significantly reduced where AST >1130 U/l, ALT >490 U/l, CPK >505 U/l, LDH >980 U/l, platelet count <23 × 10³/l, creatinine >1.4 mg/dl, INR >1.3, d-dimer >7100 ng/dl, and viral load >1.03 × 10⁸ copy/ml. Patients with 10⁸ copy/ml or higher viral load had diarrhea, headache, unconsciousness, bleeding, and seizure significantly more frequently (p < 0.05). WBC, hemoglobin, platelet counts were significantly lower whereas AST, ALT, CPK, LDH, creatinine levels, PT and aPTT time, d-dimer levels, and INR were found to be significantly higher in these group.ConclusionsThere are several severity criteria for prognosis of CCHF. In addition to these parameters, we introduce creatinine as a predictive factor for prognosis. Our study, which has the largest number of patients among studies that evaluate viral load on CCHF shows that viral load is the most effective parameter on mortality.     

The effectiveness of routine laboratory findings in determining disease severity in patients with Crimean-Congo hemorrhagic fever: Severity prediction criteria

BackgroundCrimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family.ObjectivesTo determine the predictive criteria for severity among patients with CCHF based on clinical and laboratory findings.Study designThis retrospective study was conducted on patients with CCHF and hospitalized between June 2004 and August 2008 at Karadeniz Technical University, Turkey. Demographic characteristics, clinical findings and laboratory tests on admission of all patients with CCHF were investigated.ResultsA total of 152 patients with confirmed CCHF were investigated. Sixty-three (41.4%) of these patients were in the severe group. Laboratory findings using the ROC curve method and optimum diagnostic cut-off points for specific laboratory parameters in the severe group were; PLT: 90,000, Hb: 13.5 g/dL, PT: 13.1 s, aPTT: 34 s, INR: 1, AST: 117 U/L, ALT: 71 U/L, AST/ALT: 1.62, LDH: 508 U/L, CK: 267 U/L and CRP: 0.59 mg/dL. At multivariable analysis, the risk for a severe clinical course in CCHF patients increased 2.59 and 3.93 times in the presence of platelet count and Hb below cut-off values, whereas the same risk increased 2.95, 2.92 and 3.47 times when the results for INR, AST and CRP, respectively, were above the predetermined cut-off values.ConclusionsA number of laboratory findings that can easily be measured at routine examination of patients hospitalized with a suspicion of CCHF are valuable and sensitive predictors. These parameters will contribute considerably to the design, practice and management of supportive treatment, blood and blood products replacement and intensive care services.     

Rapid chondrolysis of the knee after partial lateral meniscectomy in professional athletes

BackgroundPostoperative knee joint chondrolysis is a rare but serious complication. The aim of our study is to report the clinical presentation, the early, mid and long-term outcomes of rapid chondrolysis after a partial lateral meniscectomy in elite athletes.MethodsClinical records of 10 consecutive cases of rapid chondrolysis after partial lateral meniscectomy in eight professional athletes were retrospectively reviewed. There were seven males and one female with a mean age of 25.2 years (range 20–32 years) at index procedure. An initial conservative approach to its treatment was attempted in all cases. Arthroscopic lavage was advocated in two cases. Patients were clinically reviewed at last follow-up with comparative X-rays, a subjective IKDC, a Lysholm and Tegner scale.ResultsAll patients resumed their pre-injury level of activity at a mean 8 (± 2.45) months after the index procedure. At a mean of 82 (± 36) months of follow-up, the mean subjective IKDC, Lyshom and Tegner scale were respectively 82.64 (± 8.61), 86.6 (± 6.44), 9 (± 1.41). All knees demonstrated joint space narrowing scored Kellgren and Lawrence II (n = 1) III (n = 4) or IV (n = 5) on conventional radiographs.ConclusionBy reviewing the common factors in each of these cases we believe that rapid chondrolysis occurs primarily due to the excessive loading of the articular cartilage in the lateral compartment of the knee. In this series, although the results in the medium term were good, the long-term outcome must be guarded due to the high rate of radiographic osteoarthritis of the lateral compartment seen in this population.Study designRetrospective case series, Level IV.     

Asparagine-linked glycans determine the cytotoxic capacity of eosinophil cationic protein (ECP)

Eosinophil cationic protein (ECP) is a toxic, granule-stored protein of the eosinophil granulocyte. It is a heterogeneous protein; molecular weights can differ from 15 to 22 kDa, due to glycosylations.We purified high molecular weight ECP from blood donors with the ECP434GG (rs2073342) genotype, with the aim of examining whether removal of carbohydrates could enhance the cytotoxic capacity. The cytotoxic activity of the ECP pools was tested against the NCI-H69 cell line, before and after enzymatic deglycosylation. ECP was also analysed by SELDI-TOF MS to monitor the changes in molecular mass after deglycosylation.Five high molecular weight pools of ECP (HMW-ECP I–V) with decreasing degrees of glycosylation were tested at concentrations ranging from 0.02 to 0.6 μM. The activity ranged from EC₅₀ of >0.6 μM to 0.04 μM; HMW-ECP II had the lowest activity and HMW-ECP V the highest. After deglycosylation with N-glycosidase F, pools HMW-ECP I–III were reduced to the same molecular weight of 15.78 kDa and acquired potent cytotoxic activities. HMW-ECP IV and V with molecular species at 16.3 and 16.1 kDa were highly cytotoxic as such and were only partially deglycosylated, with slight enhancement of the toxic properties. The results suggest the presence of several HMW-ECP molecular species with differences in their post-translational modifications and cytotoxic properties.We conclude that a fraction of native ECP is stored in a non-cytotoxic form, which can be converted into a cytotoxic form by N-deglycosylation, whereas another fraction is stored as a highly cytotoxic form carrying different post-translational modifications.     

Clinical outcomes after arthroscopic treatment of knee osteoarthritis

PurposeThe aim of this study was to describe the clinical outcomes of patients with knee osteoarthritis (OA) treated with arthroscopic surgery, documenting the associated injuries and defining the type of treatment selected for OA patients with different symptoms.HypothesisKnee arthroscopy is effective for treating patients with symptomatic OA and mechanical symptoms.MethodsThis was a prospective, consecutive series of 100 patients with a clinical and radiological diagnosis of OA who were treated with knee arthroscopy. The average follow-up time was 35.9 months (25–71), and the average age was 60.1 years (50–83). Inclusion criteria: > 50 years of age, a clinical imaging diagnosis of knee OA with an Ahlbäck I–III classification. Exclusion criteria: < 50 years of age, Ahlbäck IV, pathologic lower limb mechanical axis and inflammatory joint diseases. The IKDC and Lysholm scores were assessed before and after surgery.ResultsThe preoperative average scores were as follows: Lysholm, 56.9 ± 13.5 points (22–71); IKDC, 59.4 ± 21.7 points (45–80). The postoperative average scores were as follows: Lysholm, 86.9 points (22–87); IKDC, 79.5 points (45–100). Regarding the Lysholm scores, 76% were good and excellent results and 24% were moderate (p = 0.045). The associated injuries included 48% of chondral and 36% of unstable meniscal injuries. Good or excellent results were observed in 76% of the meniscal injury cases according to the Lysholm scores, while only 84.6% of the cases with unstable chondral lesions had good or excellent results (p = 0.035).ConclusionMost patients with knee OA associated with unstable cartilage or meniscal injuries reported good-to-excellent symptomatic results at the short- and mid-term follow-ups.Level of evidenceIII     

Hepcidin-to-ferritin ratio: A potential novel index to predict iron overload-liver fibrosis in ß-thalassemia major

ObjectivesWe aimed to determine a threshold cutoff for hepcidin, ferritin, and the hepcidin-to-ferritin ratio in the diagnosis of liver fibrosis caused by iron overload in chronic hepatitis C virus (HCV)-free ß-thalassemia major patients .MethodsThis 1:1-matched case-control study included 102 individuals (3–30 yr.); 51 ß-thalassemia major patients with iron overload , and 51 apparently healthy individuals.ResultsThe highest areas under the receiver operating characteristic curves (AUC-ROCs) for the diagnosis of patients vs. controls had overlapping 95% confidence intervals (CIs): serum hepcidin (0.758; 0.64–0.87;    P ? 0.001), serum ferritin (1.000; 1.00–1.00; P  ?0.001), and the hepcidin/ferritin ratio (1.000; 1.00–1.00; P ? 0.001). For differentiation of patients with liver fibrosis stages of F0–F1 vs. F2–F4 and F0–F1 vs. F3–F4, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with P-values ? 0.001 were the only statistically significant parameters, while the AUC-ROCs of the hepcidin/ferritin ratio (0.631, P = 0.188 and 0.684, P = 0.098) exhibited 90% and 89.5% sensitivity, respectively, in staging liver fibrosis.ConclusionOur results showed that the hepcidin/ferritin ratio is as effective as the APRI and maybe a better predictor for the diagnosis of liver fibrosis and discriminating its stages, with excellent sensitivity and specificity compared to its components.     

Endothelial function,antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes

PurposeThis pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection.Patients/methodsUntreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies.ResultsTen patients were recruited (M = 8, F = 2, mean age = 51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p = 0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 μmol/L vs. 0.51 μmol/L, p = 0.45, 427.4 ng/ml vs. 307.22 ng/ml, p = 0.54, 517.70 ng/ml vs. 377.50 ng/ml, p = 0.51 and 290.75 μg/dL vs. 224.26 μg/dL, p = 0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p = 0.34).ConclusionsVenesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further.