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Louisville, KY, United States

Levinson S.S.,Robley Rex Medical Center | Levinson S.S.,University of Louisville
Clinica Chimica Acta | Year: 2012

Background: Polyneuropathy organomegaly, endocrinopathy, monoclonal (M) gammopathy, skin syndrome (POEMS) may be difficult to diagnose as a result of methodological and clinical idiosyncrasies. Four of eleven criteria (M-protein, VEGF, endocrinopathy and thrombocytosis/polycythemia) are closely associated with clinical laboratory testing. POEMS has been largely associated with λ-M-gammopathies. Vascular endothelial growth factor (VEGF) is a recent addition to the major diagnostic criteria. VEGF may alter vascular permeability causing some manifestations of POEMS. Methods: Review of the literature that focuses on clinical laboratory issues - endocrinological findings, identification of monoclonal gammopathies by electrophoresis and case demonstration. Results: Based on the criterion of VEGF, POEMS was diagnosed in a patient with a κ-M-gammopathy. Conclusions: Low-level IgA monoclonal proteins that are common in POEMS are often difficult to identify by serum electrophoresis (SPE). Immunofixation electrophoresis is required when polyneuropaties are investigated and an M-protein is not identified by SPE. VEGF may improve the sensitivity for diagnosis of POEMS and findings from capillary leak syndrome which are also associated with elevated VEGF and M-gammopathy suggests that κ-M-gammopathies may be implicated more often. It is demonstrated that due to computerized records, the laboratory practitioner is well suited to help the clinician make this complicated diagnosis. © 2012. Source


Levinson S.S.,Robley Rex Medical Center | Levinson S.S.,University of Louisville
Clinica Chimica Acta | Year: 2011

Background: With the introduction of a new sensitive serum assay for monoclonal free light chains (FLC), there is a question as to whether or not traditional urine immunofixation electrophoresis (IFE) is still necessary. Therapy for B-cell disease has greatly improved in recent time so that noninvasive biomarkers that suggest complete remissions have become increasingly important. A Consensus Opinion stated that because of methodological imperfections, at concentrations of FLC < 100. mg/l, urine IFE should supplement serum FLC ratio. Methods: Examples are presented from a review of laboratory results and medical records from 3 patients on treatment after diagnosis of amyloidosis AL and multiple myeloma. Results: Monoclonal FLC was identified in urine by IFE while the κ/λ ratio from the serum FLC assay was within the reference range. Conclusion: The results from these 3 cases suggest that as the FLC concentration drops, the serum FLC results may become more ambiguous. These results are consistent with guidelines cautioning about conclusions drawn from the serum FLC assay alone. Although more study is needed, the examples presented here illustrate that traditional urine IFE appear to adds important information regarding potential complete remissions and remains an important complementary assay to the serum FLC assay. © 2011 Elsevier B.V. Source


Levinson S.S.,Robley Rex Medical Center | Levinson S.S.,University of Louisville
Clinical Chemistry and Laboratory Medicine | Year: 2011

Articles have debated whether or not urine analysis remains valuable for identifying monoclonal gammopathies. A general impression is that the newer serum free light chain (FLC) assay is more analytically sensitive, more quantitative and simpler to perform. Many laboratory directors may have seized on the idea of eliminating urine analysis because it is a tedious procedure and requires expert interpretation while most laboratories can perform automated serum FLC assay. Others have concluded that urine immunofixation electrophoresis (IFE) optimizes the diagnostic sensitivity and should be included when there is a clinical indication. Here, I show that papers faulting urine analysis often used inappropriate urine methodology and this helps explain why there was misinterpretation. Moreover, the literature, shows urine IFE is often more sensitive for identifying low-level monoclonal FLC than the serum assay because urine IFE is as sensitive when performed appropriately and generally more specific. Besides, the reference range for serum FLC assay is unclear which is a great problem in assessing response to treatment and in identifying diseases when there is low concentration monoclonal FLC. I conclude that urine IFE remains important and is complementary to serum FLC assay, although the best algorithms for use remains to be elucidated. © 2011 by Walter de Gruyter Berlin Boston 2011. Source


Uriarte S.M.,University of Louisville | Rane M.J.,University of Louisville | Merchant M.L.,University of Louisville | Jin S.,University of Louisville | And 4 more authors.
Shock | Year: 2013

Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition of neutrophil exocytosis in vivo could be a viable therapeutic strategy. This study was conducted to determine the effect of a cell-permeable fusion protein that inhibits neutrophil exocytosis (TAT-SNAP-23) on ALI using an immune complex deposition model in rats. The effect of inhibition of neutrophil exocytosis by intravenous administration of TAT-SNAP-23 on ALI was assessed by albumin leakage, neutrophil infiltration, lung histology, and proteomic analysis of bronchoalveolar lavage fluid (BALF). Administration of TAT-SNAP-23, but not TAT-control, significantly reduced albumin leakage, total protein levels in the BALF, and intra-alveolar edema and hemorrhage. Evidence that TAT-SNAP-23 inhibits neutrophil exocytosis included a reduction in plasma membrane CD18 expression by BALF neutrophils and a decrease in neutrophil granule proteins in BALF. Similar degree of neutrophil accumulation in the lungs and/or BALF suggests that TAT-SNAP-23 did not alter vascular endothelial cell function. Proteomic analysis of BALF revealed that components of the complement and coagulation pathways were significantly reduced in BALF from TAT-SNAP-23-treated animals. Our results indicate that administration of a TAT-fusion protein that inhibits neutrophil exocytosis reduces in vivo ALI. Targeting neutrophil exocytosis is a potential therapeutic strategy to ameliorate ALI. © 2013 by the Shock Society. Source


Sethi I.,University of Louisville | Brier M.,University of Louisville | Brier M.,Robley Rex Medical Center | Dwyer A.,University of Louisville
Seminars in Dialysis | Year: 2013

At our institution, kidney biopsies are performed by an interventional nephrologist with standardized guidelines using real-time ultrasound. We hypothesized that patient factors could predict post biopsy complications. We did a retrospective review of 100 patients who underwent renal biopsy. Prebiopsy data obtained included demographics, blood pressure, laboratory studies, and kidney size. Biopsy procedure information was also recorded. Complications and post biopsy imaging was noted. A minor complication was defined as one not requiring intervention while a major complication required interventions like readmission or blood transfusion. The average age was 47years, 41 were men, 51 were black, 30 had diabetes, 42 were obese, and 81 had hypertension. Twenty-six patients had a complication; 14 minor and 12 major including 1 nephrectomy. Factors predictive of a complication were thrombocytopenia (p=0.002) and inpatient status (p=0.04). Drop in hemoglobin at 6hours was moderately sensitive and specific for a bleeding complication with an ROC of 0.723. Thrombocytopenia and inpatient status are risk factors for complications after renal biopsy. Serum creatinine, obesity, blood pressure, kidney size, needle size, and number of passes were not predictive of a major complication in our study. © 2013 Wiley Periodicals, Inc. Source

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