A case of Sjögren's syndrome in which diffuse cystic lung lesions led to an accurate diagnosis.

Key Clinical Message: Even in the absence of other symptoms or other pulmonary manifestations suggesting Sjögren's syndrome (SS), it is necessary to include SS in the differential diagnosis of diffuse cystic lung disease (CLD). Abstract: A case of SS that presented initially with diffuse CLD is reported. This case is considered rare because diffuse pulmonary cysts were observed in the early stage with few symptoms, only cysts were observed without other lung lesions on imaging, cyst formation was histologically considered to be alveolar loss, and airway lesions not observed on imaging were suspected based on lung function testing. The details of this case provide extremely important information to consider for the diagnosis and management of CLD and SS.

Detection and Characterization of Paraproteinemia in Canine Chronic B-cell Lymphocytic Leukemia Using Routine and Free Light Chain Immunofixation.

BACKGROUND: Hyperglobulinemia is reported in 26% of canine chronic B-cell lymphocytic leukemia (B-CLL) cases. However, few cases have been characterized by protein electrophoresis and immunofixation (IF), and the incidence of a monoclonal protein (M-protein) is unknown using these techniques. OBJECTIVE: To characterize and determine the proportion of canine B-CLL cases with an M-protein using plasma protein electrophoresis (PPE), routine and free light chain (fLC) IF, and to assess if productive B-CLL cases express MUM1/IRF4 by cell tube block (CTB). METHODS: PPE, routine (targeting IgG, IgA, IgM, IgG4, and light chain) and fLC IF were performed using 48 dog B-CLL plasma samples from patients diagnosed via peripheral blood flow cytometry. CTB was performed on a separate cohort of 15 patients. RESULTS: Hyperproteinemia (>7.5 g/dL) was present in 17/48 cases (35%). An M-protein was detected in 32/48 cases (67%). Of these, 19/32 cases (59%) had only complete (monoclonal heavy and light chain) M-proteins detected, 10/32 cases (31%) had both complete and fLC M-proteins detected, and 3/32 cases (9%) had only an fLC M-protein detected. IgM was the most common clonal immunoglobulin isotype detected (23 cases). CD21+ cell counts were higher in cases with detectable M-protein. Plasma fLC IF suggested ß-γ region interference, likely caused by clotting proteins. All B-CLL cases consistently expressed PAX5 and did not express MUM1/IRF4. CONCLUSIONS: Most B-CLL cases had an M-protein and were not hyperproteinemic. Most cases with paraproteins had a complete IgM monoclonal gammopathy; a subset had documented fLCs. The prognostic significance of heavy and fLC presence should be evaluated.

Pseudohyponatremia Leading to a Fatal Outcome in a Patient With Familial Hypertriglyceridemia.

Serum sodium assay is a commonly performed laboratory test in a clinical setting and the results are taken for granted without being aware of the actual methods involved. In conditions like hyperlipidemia and hyperproteinemia, excessive lipids in serum dilute the water component of the serum. Since sodium is dissolved only in the aqueous phase of serum, the sodium content per unit volume of plasma is reduced. Currently, most of the laboratories use the indirect ion-selective electrode method (ISE), where the plasma sample is diluted before the measurement. Indirect ISE may not give accurate results in conditions with higher serum lipid and protein levels. Overcorrection of the serum sodium levels in pseudohyponatremia may cause serious complications. We report a case of a 26-year-old Asian male with a past medical history of chronic pancreatitis, familial hypertriglyceridemia, and fatty liver who presented to the emergency department with acute pancreatitis. Initially, the patient was found to have hyponatremia and he was started on hypertonic saline for one day. Later the patient's condition deteriorated and then it was determined that serum sodium results were a measurement artifact since the patient had extremely high levels of triglycerides. After realizing that it was a measurement artifact, the saline infusion was stopped and he was started on desmopressin. However, the patient deteriorated neurologically and expired later. As this patient had normal sodium levels, administration of hypertonic saline led to a fatal outcome.

Discrepancies in Electrolyte Measurements by Direct and Indirect Ion Selective Electrodes due to Interferences by Proteins and Lipids.

Objectives We aim to report the simultaneous effect of different protein and lipid concentrations on sodium (Na + ) and potassium (K + ) measurement by direct and indirect ion selective electrodes (dISE and iISE) in patient samples. Materials and Methods Na + and K + were measured in 195 serum samples received in the laboratory using iISE by Roche Modular P800 autoanalyzer and using dISE by XI-921 ver. 6.0 Caretium electrolyte analyzer. Serum total protein (TP), cholesterol (Chol), and triglycerides (TG) were measured using conventional photometric methods on Roche Modular P800 autoanalyzer. Differences for each pair of results for Na + (Diff_Na + = [Na + dISE- Na + iISE ]) and K + (Diff_K + = [K + dISE- K + iISE ]) were calculated. Patient subgroups with high, normal, or low TP (< 5, 5-7.9, or ≥ 8 g/dL), Chol (< 150, 150-299, or ≥300 mg/dL), or TG (< 150, 150-299, or ≥300 mg/dL) were compared using analysis of variance. Note that 95% confidence interval of Diff_Na + and Diff_K + were calculated to see the number of samples showing clinically significant differences. Results Diff_Na + ( p = 0.007) and Diff_K + ( p = 0.002) were found significant between samples with normal and high TP. However, effect of TG was not significant. Chol concentration affected Diff_Na + significantly between low versus normal ( p = 0.002), and high versus normal ( p = 0.031) Chol groups. Diff_K + was significant ( p = 0.009) between low versus normal Chol. Clinically relevant disagreement of ≥|5| mmol/L for Na + was observed in high percentage of samples including all subcategories; however, for K + only 3.6% of the total samples showed disagreement of ≥ |0.5| mmol/L. A multivariate regression equation based on fit regression model was also derived. Conclusion Summarily, interchangeable use of electrolyte results from dISE and iISE is not advisable, especially in a setting of hyperproteinemia (≥8 g/dL) or hypercholesterolemia (≥300 mg/dL); more so for Na + .

Influence of hyperproteinemia on reproductive development in an invertebrate model.

Hyperproteinemia is a severe metabolic disease characterized by abnormally elevated plasma protein concentrations (PPC). However, there is currently no reliable animal model for PPC, and the pathological mechanism of hyperproteinemia thus remains unclear. In this study, we evaluated the effects of hyperproteinemia on reproductive development in an invertebrate silkworm model with a controllable PPC and no primary disease effects. High PPC inhibited the synthesis of vitellogenin and 30K protein essential for female ovarian development in the fat body of metabolic tissues, and inhibited their transport through the hemolymph to the ovary. High PPC also induced programmed cell death in testis and ovary cells, slowed the development of germ cells, and significantly reduced the reproductive coefficient. Furthermore, the intensities and mechanisms of high-PPC-induced reproductive toxicity differed between sexes in this silkworm model.

Alterações da proteína C reativa e fator reumatoide em cães naturalmente infectados por Leishmania spp / Changes in C-reactive protein and rheumatoid factor in dogs naturally infected by Leishmania spp

A leishmaniose visceral canina é uma zoonose considerada doença tropical de prioridade. A leishmaniose afeta vários sistemas do corpo dos cães, incluindo vísceras e pele. A proteína C reativa (PCR) e o fator reumatoide (FR) são exames realizados na medicina para detecção de inflamação e artrites em seres humanos, no entanto, há poucos trabalhos voltados para cães com leishmaniose que demonstrem as alterações ocorridas na PCR e FR. Este trabalho teve como objetivo demonstrar as alterações de PCR e FR e sua correlação com a hiperproteinemia e hiperalbuminemia, além da compararação com o desvio a esquerda presente no exame hematológico. O trabalho foi realizado no Hospital Veterinário do Centro Universitário da Grande Dourados/MS e Centro de Controle de Zoonoses, no qual foram avaliados 34 cães, de diversar raças e idade e submetidos a colheita de sangue venosa para realização de exames em imuno-látex, bioquímica sérica e hemograma, em cães naturalmente infectados por Leishmania spp. Foram utilizados somente cães positivos ao teste rápido DPP® para leishmaniose, juntamente com resultado positivo no exame parasitológico, depois de diagnosticados foram realizados exames hematológicos e bioquímicos. Quando realizado o teste para quantificação de FR em soro sanguíneo, para os 34 animais estudados, foi observado positividade em apenas 1 animal, enquanto que os cães foram positivos para a PCR em 38,23% dos casos estudados. Em casos de animais com leishmaniose é possível estabelecer níveis inflamatórios precocemente, enquanto que o FR demonstrou não ser um bom marcador para animais soropositivos para a doença.(AU)

Canine visceral leishmaniasis is a zoonosis considered a priority tropical disease. The disease affects various body systems of dogs, including viscera and skin. C-reactive protein (CRP) and rheumatoid factor (RF) are tests performed in medicine for the detection of inflammation and arthritis in humans, however, there are few studies aimed at dogs with leishmaniasis that demonstrate changes in CRP and RF. This work aimed to demonstrate the changes of CRP and RF and its correlation with hyperproteinemia and hyperalbuminemia, in addition to the comparison with the left deviation present in the hematological examination. The work was carried out at the Veterinary Hospital of the University Center of Grande Dourados/MS and Zoonoses Control Center, in which 34 dogs of different breeds and ages were submitted to venous blood collection for immuno-latex exams, Biochemistry and blood count in dogs naturally infected with Leishmania spp. Only dogs to the DPP® rapid test for leishmaniasis were used, together with a positive result in parasitological examination, after hematological and biochemical tests were performed. When the test for the quantification of FR in serum was performed, for the 34 animals studied, positivity was observed in only 1 animal, while the dogs were PCR positive in 38.23% of the cases studied. In cases of animals with leishmaniasis it is possible to establish inflammatory levels early, whereas the FR showed not to be a good marker for animals seropositive for the disease.(AU)

Induced Hyperproteinemia and Its Effects on the Remodeling of Fat Bodies in Silkworm, Bombyx mori.

Hyperproteinemia, which is characterized by an abnormally elevated plasma protein concentration (PPC), is a high-mortality, metabolic complication associated with severe liver and kidney disease. It is difficult to clinically distinguish the difference between the impacts of primary diseases and hyperproteinemia on tissues and organs, and there are no available animal models of hyperproteinemia. Here, we constructed an animal model of hyperproteinemia with a controllable PPC and no primary disease effects in the silkworm Bombyx mori that has attracted interest owing to its potential use in the pathological analysis of model animals. Silkworm have an open circulatory system in which each organ is directly immersed in hemolymph. The fat body (FB) of a silkworm, as a major organ for nutrient storage and energy metabolism, can effectively reflect hyperproteinemia-induced metabolic abnormalities in damaged visceral tissues. A pathogenesis study showed that hyperproteinemia attenuated cell autophagy and apoptosis by attenuating an endocrine hormone, thereby preventing FB remodeling during metamorphosis. Meanwhile, hyperproteinemia increased oxidative stress in the FB and resulted in a dysfunction of amino acid conversion. Supplementation with exogenous 20-hydroxyecdysone effectively mitigated the hyperproteinemia-mediated inhibition of FB remodeling.

Prevalence and Predictors of Cholesterol Screening, Awareness, and Statin Treatment Among US Adults With Familial Hypercholesterolemia or Other Forms of Severe Dyslipidemia (1999-2014).

BACKGROUND: Familial hypercholesterolemia (FH) and other extreme elevations in low-density lipoprotein cholesterol significantly increase the risk of atherosclerotic cardiovascular disease; however, recent data suggest that prescription rates for statins remain low in these patients. National rates of screening, awareness, and treatment with statins among individuals with FH or severe dyslipidemia are unknown. METHODS: Data from the 1999 to 2014 National Health and Nutrition Examination Survey were used to estimate prevalence rates of self-reported screening, awareness, and statin therapy among US adults (n=42 471 weighted to represent 212 million US adults) with FH (defined using the Dutch Lipid Clinic criteria) and with severe dyslipidemia (defined as low-density lipoprotein cholesterol levels ≥190 mg/dL). Logistic regression was used to identify sociodemographic and clinical correlates of hypercholesterolemia awareness and statin therapy. RESULTS: The estimated US prevalence of definite/probable FH was 0.47% (standard error, 0.03%) and of severe dyslipidemia was 6.6% (standard error, 0.2%). The frequency of cholesterol screening and awareness was high (>80%) among adults with definite/probable FH or severe dyslipidemia; however, statin use was uniformly low (52.3% [standard error, 8.2%] of adults with definite/probable FH and 37.6% [standard error, 1.2%] of adults with severe dyslipidemia). Only 30.3% of patients with definite/probable FH on statins were taking a high-intensity statin. The prevalence of statin use in adults with severe dyslipidemia increased over time (from 29.4% to 47.7%) but not faster than trends in the general population (from 5.7% to 17.6%). Older age, health insurance status, having a usual source of care, diabetes mellitus, hypertension, and having a personal history of early atherosclerotic cardiovascular disease were associated with higher statin use. CONCLUSIONS: Despite the high prevalence of cholesterol screening and awareness, only ≈50% of adults with FH are on statin therapy, with even fewer prescribed a high-intensity statin; young and uninsured patients are at the highest risk for lack of screening and for undertreatment. This study highlights an imperative to improve the frequency of cholesterol screening and statin prescription rates to better identify and treat this high-risk population. Additional studies are needed to better understand how to close these gaps in screening and treatment.

Double filtration plasmapheresis in the treatment of hyperproteinemia in dogs affected by Leishmania infantum.

Three dogs were evaluated for severe hyperproteinemia and hyperglobulinemia secondary to Leishmania infantum. Double filtration plasmapheresis (DFPP) was performed in two dogs at days 1, 2, and 6 after presentation. The third dog received DFPP at days 1 and 3 after presentation and eleven hemodialysis treatments. Significant reduction in serum total protein (p ＜ 0.0001), alpha-1 (p = 0.023), alpha-2 (p = 0.018), gamma globulins (p = 0.0105), and a significant increase in albumin/globulin ratio (p = 0.0018) were found. DFPP may be a promising therapeutic technique for rapid resolution of signs of hyperproteinemia in dogs affected by L. infantum.

Double filtration plasmapheresis in the treatment of hyperproteinemia in dogs affected by Leishmania infantum

Three dogs were evaluated for severe hyperproteinemia and hyperglobulinemia secondary to Leishmania infantum. Double filtration plasmapheresis (DFPP) was performed in two dogs at days 1, 2, and 6 after presentation. The third dog received DFPP at days 1 and 3 after presentation and eleven hemodialysis treatments. Significant reduction in serum total protein (p < 0.0001), alpha-1 (p = 0.023), alpha-2 (p = 0.018), gamma globulins (p = 0.0105), and a significant increase in albumin/globulin ratio (p = 0.0018) were found. DFPP may be a promising therapeutic technique for rapid resolution of signs of hyperproteinemia in dogs affected by L. infantum.

Abnormal gel flotation in a patient with apperant pneumonia diagnosis: a case report.

INTRODUCTION: Serum blood collection tubes with separator gel are widely used by many laboratories for chemistry analyses. We describe a case of a primary blood collection tube filled with blood sample and a floating separator gel. MATERIALS AND METHODS: The blood sample was collected from a 51 years old female in intensive care unit with the diagnosis of pneumonia into a BD Vacutainer SST tube (Becton Dickinson, NJ, USA) containing serum separator gel and conveyed to the core laboratory of Marmara University Hospital within 30 minutes from collection. Sample was immediately centrifuged at room temperature at 1500 × g for 10 minutes. RESULTS: The analyses revealed a highly increased total protein concentration of 145 g/L (reference interval 64-83 g/L). The nephelometric analyses showed an elevated serum IgG concentration of 108 g/L (reference interval 6.5-16 g/L) and IgG lambda monoclonal band was determined by serum immunofixation electrophoresis. CONCLUSION: Limitation of the separator gel tubes in patients with a high plasma density and its possible effects on test results and laboratory costs should be remembered. The clinical diagnosis stated in the information system should also reveal known comorbid conditions besides the apparent admission reason. This information would avoid resampling, additional testing, and communication efforts with the clinicians.

Qualidade espermática de sêmen de cães naturalmente infectados por leishmania sp / Semen quality of dogs naturally infected by leishmania sp

Avaliaram-se alterações espermáticas associadas à infecção por leishmaniose no sêmen de cães naturalmente infectados, utilizando-se, durante oito semanas consecutivas, ejaculados de seis cães soronegativos e seis cães soropositivos. As amostras foram colhidas uma vez por semana e avaliadas quanto ao volume, concentração, motilidade, vigor, morfologia espermática, integridade da cromatina, avaliação simultânea da integridade da membrana plasmática, acrossoma e potencial mitocondrial. Concomitantemente foram dosadas a proteína total do plasma seminal e sanguíneo. A leishmaniose visceral causou aumento dos defeitos maiores e menores nos espermatozoides dos animais acometidos pelo estágio moderado a severo da doença. Em estágios mais avançados da enfermidade, a integridade das membranas acrossomal e plasmática foi afetada negativamente. Não foi possível estabelecer um critério quanto à avaliação do potencial mitocondrial. A incidência de alterações morfológicas nos animais acometidos não promoveu aumento de injurias à cromatina. Todos os animais com leishmaniose apresentaram hiperproteinemia do sêmen.

The spermatic changes associated with the natural infection in dogs by Leishmania sp was evaluated during eight consecutive weeks, using ejaculates of six seronegative and six seropositive dogs. The samples were collected once a week and evaluated for volume, concentration, motility, vigor, sperm morphology, chromatin integrity, simultaneous evaluation of the plasmatic membrane integrity, acrosome, and mitochondrial potential. The total proteins of the seminal plasma and blood were measured. The visceral leishmaniasis caused increase of major and minor defects in spermatozoa of animals attacked by moderate to severe stages of the disease. In more advanced stages of the illness, the acrosomal and plasmatic membranes integrity was adversely affected. It was not possible to establish a pattern refering the evaluation of the mitochondrial potential. The incidence of morphological changes in the seropositive animals did not promote an increase of injuries to the chromatin. All animals with leishmaniasis presented hyperproteinemia of the semen.

Pseudohyponatremia: does it matter in current clinical practice?

Serum consists of water (93% of serum volume) and nonaqueous components, mainly lipids and proteins (7% of serum volume). Sodium is restricted to serum water. In states of hyperproteinemia or hyperlipidemia, there is an increased mass of the nonaqueous components of serum and a concomitant decrease in the proportion of serum composed of water. Thus, pseudohyponatremia results because the flame photometry method measures sodium concentration in whole plasma. A sodium-selective electrode gives the true, physiologically pertinent sodium concentration because it measures sodium activity in serum water. Whereas the serum sample is diluted in indirect potentiometry, the sample is not diluted in direct potentiometry. Because only direct reading gives an accurate concentration, we suspect that indirect potentiometry which many hospital laboratories are now using may mislead us to confusion in interpreting the serum sodium data. However, it seems that indirect potentiometry very rarely gives us discernibly low serum sodium levels in cases with hyperproteinemia and hyperlipidemia. As long as small margins of errors are kept in mind of clinicians when serum sodium is measured from the patients with hyperproteinemia or hyperlipidemia, the present methods for measuring sodium concentration in serum by indirect sodium-selective electrode potentiometry could be maintained in the clinical practice.

Pseudohyponatremia:Does It Matter in Current Clinical Practice?

Serum consists of water (93% of serum volume) and nonaqueous components, mainly lipids and proteins (7% of serum volume). Sodium is restricted to serum water. In states of hyperproteinemia or hyperlipidemia, there is an increased mass of the nonaqueous components of serum and a concomitant decrease in the proportion of serum composed of water. Thus, pseudohyponatremia results because the flame photometry method measures sodium concentration in whole plasma. A sodium-selective electrode gives the true, physiologically pertinent sodium concentration because it measures sodium activity in serum water. Whereas the serum sample is diluted in indirect potentiometry, the sample is not diluted in direct potentiometry. Because only direct reading gives an accurate concentration, we suspect that indirect potentiometry which many hospital laboratories are now using may mislead us to confusion in interpreting the serum sodium data. However, it seems that indirect potentiometry very rarely gives us discernibly low serum sodium levels in cases with hyperproteinemia and hyperlipidemia. As long as small margins of errors are kept in mind of clinicians when serum sodium is measured from the patients with hyperproteinemia or hyperlipidemia, the present methods for measuring sodium concentration in serum by indirect sodium-selective electrode potentiometry could be maintained in the clinical practice.