Elevated Total Protein Concentrations Research Articles

A tick bite patient with fever and meningitis co-infected with Rickettsia raoultii and Tacheng tick virus 1: a case report

BackgroundIncreasing numbers of tick-borne pathogens are being discovered, including those that infect humans. However, reports on co-infections caused by two or more tick-borne pathogens are scarce.Case presentationA 38-year-old male farmer was bitten by a hard tick, presented with fever (37.7 °C), severe headache and ejection vomiting. Lumbar puncture was performed in the lateral decubitus. The cerebrospinal fluid (CSF) was clear, and analysis showed severe increased pressure (320 mm H2O), mild leukocytosis (126.0 × 106/L, mononuclear cells accounting for 73%) and elevated total protein concentration (0.92 g/L). Bacterial cultures of CSF and blood were negative. The diagnosis of Rickettsia raoultii and Tacheng tick virus 1 (TcTV-1) co-infection was confirmed by amplifying four rickettsial genetic markers and the partial small (S) RNA segment of TcTV-1 from the patient’s blood. The patient gradually recovered after treatment with levofloxacin and ribavirin.ConclusionsThis is the first reported co-infection case with fever and meningitis caused by R. raoultii and TcTV-1. It is vital to screen for multiple pathogens in tick-bitten patients, especially in those with severe complex symptoms.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

RT-QuIC: a new test for sporadic CJD

The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) can be difficult, but the real-time quaking-induced conversion (RT-QuIC) assays have made a considerable impact on its clinical diagnosis. This technique exploits the...

Ethylenediaminetetraacetic acid (EDTA) anticoagulant affects the refractometric measurement of total protein concentration in equine synovial fluid

SummaryThe objectives of this study were to (i) determine the effect of ethylenediaminetetraacetic acid (EDTA) concentration on the refractometric measurement of the total protein (TP) concentration of equine synovial fluid and (ii) assess the effect of time and temperature on the refractometric measurement of TP concentration. Synovial fluid was retrieved aseptically from horses presenting to Liphook Equine Hospital either (a) immediately after euthanasia or (b) from those requiring arthrocentesis as part of their clinical investigation. Samples were aliquoted into commercially available (i) plain tubes (0.5 mL; control) and (ii) EDTA tubes (at different volumes to obtain serial dilutions of EDTA:synovial fluid). TP concentration was measured by two independent observers using a calibrated hand‐held refractometer. Samples from a separate group of horses were stored for 24 h at 4°C and 20°C before analysis to assess the effects of time and temperature. Results were compared using repeated measures ANOVA. TP concentration was significantly higher at all EDTA concentrations compared to control samples, with the greatest effect seen with higher concentrations (P<0.0001 for samples with ≥3.17 mg EDTA/mL). Storage time or temperature did not significantly affect TP concentration. Refractometric measurement of small volumes of synovial fluid in commercially available EDTA tubes leads to artificially elevated TP concentrations. Delays in sample analysis and alterations in storage conditions did not significantly affect TP concentration within the parameters studied. The magnitude of overestimation of synovial total protein concentration could result in misclassification of suspect synovial sepsis cases where EDTA tubes are used.

Therapeutic Use of Regional Limb Perfusion in a Chicken

A 2-year-old, 3.8-kg male Rhode Island red rooster was examined for lameness and progressive swelling of the right foot of several month's duration. Radiographs of the right foot demonstrated soft tissue swelling and a smoothly marginated periosteal reaction evident of inflammation affecting the bones. Results of a complete blood count showed a moderate leukocytosis and an elevated total protein concentration. Systemic antibiotic and anti-inflammatory therapy was started, but the bird had not improved at recheck examination. After intravenous catheterization of the medial metatarsal vein and placing a tourniquet at the femoral-tibiotarsal joint of the right leg, regional limb perfusion with amikacin and flunixin meglumine was performed. Dimensions of both feet were measured with digital calipers, and surface temperatures of the feet were measured with an infrared thermometer. The rooster had improved activity level with decrease in lameness and measurable decrease in swelling of the right foot. Regional limb perfusion with intravenous antibiotics and nonsteroidal anti-inflammatory drugs is a viable treatment modality in avian species for suspected distal limb infection and cellulitis. This technique has potential valuable implications for a variety of avian species. Fluid support should be provided if using nephrotoxic drugs.

Clinicopathological and ultrasonographic findings in 40 water buffaloes (Bubalus bubalis) with traumatic pericarditis

Forty buffaloes with traumatic pericarditis were examined to characterise the ultrasonographic findings in buffaloes with traumatic pericarditis, determine the extent of the lesions and assess the prognosis. The most noticeable...

Increased Gamma Globulin Following Immunotherapy with Sipuleucel-T Is Associated with Antigen-Specific Antibody Responses

AbstractAbstract 1738Sipuleucel-T is an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated with a recombinant human protein, PAP-GM-CSF (prostatic acid phosphatase [PAP] linked to granulocyte-macrophage colony-stimulating factor [GM-CSF]). It is prepared from cells collected by leukaphereses at Weeks 0, 2, and 4 and infused approximately 3 days following each leukapheresis. In the IMPACT study, 512 patients were randomized (2:1) to sipuleucel-T or control (non-activated autologous PBMCs). Serum samples were collected at Baseline and Weeks 6, 14, and 26, and were analyzed for routine clinical chemistry tests in a comprehensive metabolic panel, which included total protein and albumin. In selected samples, serum protein electrophoresis (SPEP) and densitometry were performed using the Sebia automated electrophoresis system. We observed elevated total protein at Weeks 6 and 14 in sipuleucel-T patients only. At Week 6, 10.0% (28/279) of sipuleucel-T patients with a normal baseline total protein concentration had an elevated total protein concentration (upper limit of normal [ULN] = 7.9 to 8.5 g/dL, depending on age) compared with 0% (0/140) of control patients. At Week 14, 10.4% (19/183) of sipuleucel-T patients with a normal baseline total protein had an elevated total protein compared with 0% (0/86) of control patients. Albumin levels were not elevated at Week 6 following treatment (0.4% ½84 of sipuleucel-T patients with a normal baseline albumin concentration had increases in post-treatment serum albumin), indicating that the changes in total protein were due to elevations in serum globulin. In sipuleucel-T patients, there was a positive correlation between the maximum globulin protein elevations (total protein minus albumin) and the magnitude of antibody titers to PAP-GM-CSF at Week 6 (n = 126; P = 0.001) and Week 14 (n = 85; P = 0.002). Samples from sipuleucel-T patients for whom both a baseline and post-treatment sample were available and who fell within the upper 10th percentile of the total protein change (n = 13) were evaluated by SPEP. All of these patients had increased gamma globulin compared with baseline. Nine patients (69.2%) developed gamma globulin above the upper limit of normal (i.e., > 1.5 g/dL) which was not present at baseline. A correlation between gamma globulin elevations and antibody titers to PAP-GM-CSF in these patients (n = 9) was observed at Week 6 (r = 0.664, P = 0.051). These data demonstrate that elevated gamma globulin levels can develop following treatment with sipuleucel-T and were associated with the development of an antigen-specific humoral response. Disclosures:Sims:Dendreon Corp.: Employment. dela Rosa:Dendreon Corp.: Employment. Lin:Dendreon Corp.: Employment. Sheikh:Dendreon Corp.: Employment.

An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain Barré syndrome

Elevated cerebrospinal fluid (CSF) total protein (TP) concentration (mainly due to a dysfunctional blood-CSF barrier (B-CSFB)) with normal cell count is a hallmark for the diagnosis of Guillain-Barriota syndrome (GBS). This work presents the evaluation of B-CSFB dysfunction with respect to the course, severity, and clinical features of GBS. A sample of CSF was collected on admission from 68 patients of both genders (15 children and 53 adults) diagnosed with GBS. A follow-up CSF sample was obtained approximately 15 days after admission. TP concentration was determined in the CSF and 7.5% polycrylamide gel electrophoresis was employed for serum and CSF protein fractioning. A low percentage of prealbumin fraction was considered a test of impaired B-CSFB. Elevated TP concentration and lower prealbumin were observed in almost 70% of the patients on admission, but this percentage was lower (52.4%) during the first week from onset of symptoms. Both variables were directly associated with the time of evolution of the disease and also with a greater clinical severity. Follow-up CSF studies showed higher CSF TP and lower prealbumin percentages, while deceased patients did not display this response pattern in the follow-up CSF. B-CSFB dysfunction was present in only half of the patients with GBS during the first week from onset and it was directly associated with progression and clinical severity; nevertheless, a low B-CSFB dysfunction response during follow-up was associated with a lethal outcome, suggesting it could also serve a 'protective' effect during regeneration.

CSF findings in patients with voltage gated potassium channel antibody associated limbic encephalitis

Recently, a new subtype of limbic encephalitis (LE) has been described, serologically characterized by the presence of antibodies against voltage gated potassium channels (VGKC, to be called VGKC-LE). Only little is known about CSF findings in this new disorder. Here we report the results of 29 lumbar punctures in 17 patients with VGKC-LE. Slight pleocytosis, mainly consisting of lymphocytes and monocytes, and elevated total protein concentrations were present in 41 and 47%, respectively. Intrathecal immunoglobulin (Ig) synthesis as defined by the presence of CSF-specific oligoclonal IgG bands, an increased IgG index, or an elevated IgG, IgA, or IgM ratio, was not detected in any of the patients, but dysfunction of the blood-CSF barrier was found in 35%. CSF findings were normal in 23%. Unlike paraneoplastic LE, VGKC-LE is not frequently associated with intrathecal Ig production or markedly elevated white cell counts. Thus, normal CSF findings do not preclude the disease. VGKC-Ab should, therefore, be determined whenever LE is clinically suspected, irrespective of the presence or absence of inflammatory CSF changes.

Severe Ascites with Hypothyroidism and Elevated CA125 Concentration: A Case Report

Ascites caused by hypothyroidism is rare and the pathogenesis is unclear. Several reports have presented cases of progressive ascites with hypothyroidism and elevated tumor markers. We report a 31-year-old female case with massive ascites and elevated serum CA 125 concentrations. The patient had no typical feature of hypothyroidism except an accumulation of ascitic fluid which showed elevated total protein concentration and a high serum-ascites albumin gradient (SAAG). There was no finding of malignancy. Following thyroid hormone replacement, the ascites was completely resolved accompanied by reduced concentrations of serum CA125. In general, primary hypothyroidism with ascites presents with coexisting massive pericardial or pleural effusion. The massive ascites and increased serum CA125 concentrations may have led us to make the incorrect diagnosis of ovarian malignancy. The evaluation of thyroid function is useful to determine the pathology of high-protein ascites or elevated tumor markers, and ascites may be treatable by thyroid replacement therapy.

Monoclonal Gammopathy of Undetermined Significance

A 58-year-old man with no significant medical history is found to have an elevated total protein concentration (8.1 g per deciliter) on a routine blood chemical study. He is asymptomatic, and his physical examination is normal. Serum protein electrophoresis reveals a monoclonal spike of 2.1 g per deciliter at the gamma region; immunofixation shows a monoclonal IgG kappa protein. What further evaluation is warranted, and assuming the diagnosis of monoclonal gammopathy of undetermined significance is made, how should the patient be followed?

Direct adenovirus-mediated IGF-I gene transduction of synovium induces persisting synovial fluid IGF-I ligand elevations

Insulin-like growth factor-I (IGF-I) is one of the most influential growth factors in cartilage repair. Maintenance of adequate IGF-I levels after articular repair procedures is complicated by the short biological half-life of IGF-I in vivo. This study investigated the potential for more prolonged IGF-I delivery through direct adenoviral mediated transduction of synovial tissues in the metacarpophalangeal (MCP) joints of horses. The use of a large animal model provided a structurally similar and metabolically relevant corollary to the human knee. The complete IGF-I coding sequence was packaged into an E1-E3 deleted adenovirus-5 vector under cytomegalovirus promoter control (AdIGF-I), and injected at varying total joint doses to the MCP joints of 14 horses. Direct injection of 20 and 50 x 10(10) AdIGF-I resulted in significant elevations of IGF-I in synovial fluid for approximately 21 days. Synovial tissue taken from injected joints at day 35 following injection and compared to tissue taken preinjection from the same joints revealed elevated synoviocyte IGF-I mRNA levels for the highest viral dose by in situ hybridization and real-time PCR techniques. AdIGF-I injections did not result in significant lameness, joint effusion or elevated total protein concentrations in the synovial fluid. Mild mononuclear infiltration of white blood cells was evident in histologic sections of the synovium in the second highest adenoviral IGF-I dose of 20 x 10(10) particles. Cartilage biopsies taken from all injected joints did not reveal any significant changes in proteoglycan levels nor in histological morphology, which included chondrocyte cloning, architecture, cell type or toluidine blue staining, when compared to control joints. Based on these findings, gene transfer of IGF-I to the synovium of joints can result in significant and persistent elevations of IGF-I ligand in synovial fluid with minimal detrimental effects. Direct IGF-I gene therapy may offer a simple approach in treating patients with acute cartilage injury.