Catch the Calcium: T-Cell Histiocyte-Rich B-Cell Lymphoma Presenting as Hypercalcemia.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is an extremely rare and aggressive subtype of diffuse large B-cell lymphoma (DLBCL) that typically presents in middle-aged patients and carries a poor prognosis. Hypercalcemia presenting as the initial manifestation of the disease is rare, with only one other case reported in the literature. We report a case of a 90-year-old male who presented with progressive lethargy and unintentional weight loss. Initial workup showed elevated serum calcium of 14.6 mg/dL, corrected for albumin, and creatinine of 1.51 mg/dL. He had a suppressed iPTH of 6.3 pg/mL and normal PTHrP (13 pg/mL). Computed tomography (CT) scan of the abdomen and pelvis was performed to rule out underlying malignancy, which showed splenomegaly and enlarged retrocrural and porta hepatis lymph nodes. Bone marrow biopsy was performed to evaluate for hematological malignancy, which revealed findings diagnostic of THRLBCL. While rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the mainstay therapies for DLBCL and has been shown to have comparable outcomes in THRLBCL, there are documented concerns with its toxicity profile limiting the ability of older patients (60 years and older) to complete therapy. Our patient was treated with R-mini-CHOP, which is much better tolerated in this patient demographic. R-mini-CHOP features decreased doses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with the conventional dose of rituximab. This case discusses a rare subtype of non-Hodgkin lymphoma presenting with a unique manifestation of hypercalcemia. We highlight the importance of thorough investigation for causes of hypercalcemia as well as the efficacy and tolerability of R-mini-CHOP in this elderly patient demographic.

The Diagnostic and Treatment Challenges of Concomitant Mantle Cell Lymphoma and IgM Myeloma.

It is rare for IgM multiple myeloma (MM) and mantle cell lymphoma (MCL) to coexist. Furthermore, it is challenging to demonstrate if there are two distinct types of neoplasia or if plasma cell differentiation of MCL is present. We discuss the case of a patient concomitantly diagnosed with MCL and IgM MM, and the subsequent diagnostic and management difficulties, and the positive treatment outcome. LEARNING POINTS: Due to the rarity of simultaneous multiple myeloma (MM) and mantle cell lymphoma (MCL), it is challenging to investigate a possible association.This report will draw attention to the condition's rarity, diagnostic and treatment hurdles, and hopefully inspire future research into therapeutic alternatives.Several recent developments indicate a bright future for treating refractory malignancies such as MM and MCL, such as the advent of chimeric antigen receptor T-cell (CAR T-cell) therapy.

Reliability of combined fine needle aspiration and core needle biopsies in the diagnosis of liver lesions: An 8-year institutional experience.

OBJECTIVE: Fine needle aspiration (FNA), followed by core needle biopsy (CNB) when needed, was adopted as the standard care for liver lesions in our institution. This study explores the diagnostic efficacy of combined image-guided FNA and CNB in liver lesion diagnosis. METHOD: We retrospectively reviewed all liver FNA cases performed in our institution between January 2010 and September 2018. A total of 550 cases from 531 patients (173 females) with a median age of 59 years (range, 13-90) were identified. All FNA cases were initially assessed with rapid on-site evaluation, and cell blocks were prepared. A total of 459 FNA specimens with concurrent CNBs were included in the study. Both FNAs and CNBs in the paired sampling were read by a cytopathologist, with expert consultation as needed. RESULTS: The concordance rate between FNA and CNB was 85.2%. Combined FNA/CNB showed higher sensitivity in detecting malignant tumours when compared to FNA or CNB alone (98%, vs 87% and 92%, p < 0.001), especially for detecting metastatic tumours, hepatocellular carcinoma, and haematopoietic neoplasms (98%, 97%, and 94%, respectively; all p < 0.001). Combined FNA/CNB showed a lower false negative rate in malignant tumours than FNA or CNB alone (2%, vs 13% and 8%, p < 0.001). There was no significant difference among FNA, CNB, and combined FNA/CNB in diagnosing benign liver lesions. CONCLUSIONS: Combined liver FNA/CNB has high diagnostic efficacy for malignancy and a lower false negative rate than either procedure alone, especially in metastatic tumours, hepatocellular carcinoma, and haematopoietic neoplasms.

Outcome of atypia of undetermined significance/follicular lesion of undetermined significance in thyroid fine-needle aspirations: A six-year institutional experience.

BACKGROUND: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is one of six diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). The goal of our study is to assess the outcome of cases classified as AUS/FLUS at our institution. METHODS: AUS/FLUS cases were identified by computer searching of the thyroid fine-needle aspiration (FNA) cases performed between 2010 and 2016. Outcomes were categorized as: follow-up surgery, repeat FNA or no follow-up available. Demographics, ultrasound findings and FNA diagnostic criteria were reviewed for AUS/FLUS cases with follow-up surgical pathology diagnosis. RESULTS: Our AUS/FLUS thyroid FNA rate was 6% (117 out of 1984 FNAs). Only 15% of the AUS/FLUS cases had repeat FNA, while 41% underwent surgery. The risk of malignancy (ROM) for cases with follow-up surgery was 17%. When considering all AUS/FLUS cases, the ROM was 7%. Statistically, benign neoplasms were more likely to be single lesions on ultrasound comparing to malignant neoplasms, and to exhibit architectural atypia as opposed to non-neoplastic lesions on FNA. The malignancy rates among patients that directly went to surgical resection (17%) and patients having repeat FNA after the first AUS/FLUS diagnosis followed by surgery (29%) was not significantly different. However, repeat FNA was able to reclassify the majority of cases into more definitive categories. CONCLUSION: The outcome of the thyroid FNAs diagnosed as AUS/FLUS in our institution meets the benchmark statistics for AUS/FLUS rate and ROM. This study constitutes a valuable quality assurance measure and serves as a baseline for subsequent quality improvement.

Gamna-Gandy bodies in fine-needle aspiration from abdominal splenosis: A clue to underlying portal hypertension.

A 40-year-old woman presented with abdominal pain and jaundice. Past medical history was significant only for splenectomy following a motor vehicle accident. Owing to presence of multiple peritoneal nodules on computerized tomography (CT) and elevated serum CA-125, ovarian peritoneal carcinomatosis was suspected. Ultrasound-guided fine-needle aspiration (FNA) revealed presence of abundant hemosiderin, leukocytes, endothelial cells, and fungal hypha-like structures. No evidence of neoplasia was found. Findings were consistent with Gamna-Gandy bodies (GGBS) within splenic tissue. Based on history of splenectomy and FNA findings, a diagnosis of abdominal splenosis with presence of GGBS was made. Workup for hepatic cirrhosis and portal hypertension was recommended. Liver biopsy confirmed presence of cirrhosis. To our knowledge, this is the first report of GGBS identified within abdominal splenosis. It is important for pathologists to be able to recognize GGBS and to be aware of their relationship to portal hypertension and other conditions associated with severe vascular congestion or hemorrhage. History and pathogenesis of GGBS, their diagnostic morphologic features and a review of cases of GGBS diagnosed via cytology are given.

Dual Expression of TCF4 and CD123 Is Highly Sensitive and Specific For Blastic Plasmacytoid Dendritic Cell Neoplasm.

The diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) has been based on the expression status of multiple markers, including CD123. TCF4 was discovered recently to be an obligatory master regulator of plasmacytoid dendritic cells. We postulated that a tissue-based assay designed to detect dual CD123 and TCF4 expression would provide a highly reliable and practical marker for BPDCN in biopsy material. We designed, optimized, and validated a dual-color TCF4/CD123 immunohistochemistry stain for use in formalin-fixed paraffin-embedded tissue sections. The performance characteristics of the TCF4/CD123 stain were evaluated in 48 confirmed BPDCN cases. TCF4/CD123 coexpression was detected reproducibly in plasmacytoid dendritic cells. In BPDCN, the TCF4/CD123 stain showed coexpression in all (48/48; 100%) cases analyzed. Cases with concurrent samples from different anatomic sites showed comparable staining characteristics. In contrast, of 464 non-BPDCN cases comprising a wide range of hematolymphoid neoplasms and cutaneous lesions that might enter in the differential diagnosis of BPDCN, we identified dual expression of TCF4 and CD123 in only 1 case of B-lymphoblastic leukemia/lymphoma. On the basis of these findings, the TCF4/CD123 dual-color immunohistochemical stain had an analytic sensitivity of 100% and a specificity of 99.8%. Receiver operator characteristic analysis demonstrated an area under the curve of 1.000 (95% confidence interval: 0.999-1.000). In summary, the dual-color TCF4/CD123 immunohistochemistry stain provides a robust standalone and cost-effective assay for the diagnosis of BPDCN.

Early T precursor acute lymphoblastic leukaemia/lymphoma shows differential immunophenotypic characteristics including frequent CD33 expression and in vitro response to targeted CD33 therapy.

The differential immunophenotypic characteristics of early T precursor (ETP) acute lymphoblastic leukaemia/lymphoma (ALL) remain incompletely characterized. The study group (n = 142) included 106 (74·7%) men and 36 (25·3%) women with a median age of 34·9 years (range, 2-79) at diagnosis. Patients were subtyped by flow cytometry immunophenotyping as follows: 33 (23·2%) ETP; 32 (22·5%) early non-ETP; 60 (42·2%) thymic; and 17 (12·1%) mature. Excepting definitional markers, there was a significant differential expression of the markers CD2, CD10, CD33 and TdT between ETP-ALL and non-ETP-ALL. Positive CD33 expression (≥20% of leukaemic blasts) was detected in 21/33 (63%) ETP-ALL compared with 17/95 (17·9%) non-ETP-ALL (P < 0·001). Notably, targeted anti-CD33 therapy with IMGN779 resulted in significant growth inhibition and increased apoptosis in ETP-ALL cells in vitro. An 11-marker T-ALL immunophenotype score discriminated reliably between ETP and non-ETP ALL. Longitudinal analysis of ETP-ALL cases in this study demonstrated that the immunophenotype may be occasionally dynamic but is largely stable over the disease course. In summary, identification of ETP-ALL might be enhanced by using an 11-marker T-ALL immunophenotype score. CD33 expression is frequent in ETP-ALL, and in vitro data suggest that exploring anti-CD33 therapy in ETP-ALL is warranted.

IgM plasma cell myeloma in the era of novel therapy: a clinicopathological study of 17 cases.

IgM plasma cell myeloma (PCM) is a rare subtype of myeloma, and its response to novel therapies has not been fully characterized. We describe clinicopathological features and outcome of 17 patients with IgM PCM (11 men and 6 women) with a median age of 63 years. Patients presented with serum hyperviscosity (77%), bone lesions (71%), anemia (65%), renal dysfunction (53%), and hypercalcemia (35%). Median serum IgM level was 6.4 g/dL (0.7-12.1 g/dL). Bone marrow plasma cells (median, 80%; range, 20%-90%) were frequently of lymphoplasmacytic type (8/17; 47%). Immunophenotypically, the myeloma cells were positive for CD38, CD138, CD20 (5/16; 31%), CD56 (4/16; 25%), and CD117 (2/12; 17%); negative for CD19; and decreased or absent CD27 and CD81 in all cases. Seven (41%) patients had a complex karyotype, and fluorescence in situ hybridization showed CCND1-IGH (13/16; 81%), and deletions of 17p13/TP53 (29%) and 13q14/RB1 (38%). No MYD88 L265P mutation was detected. Most patients (94%) received proteasome inhibitor with or without immunomodulatory drug, 62% of patients required multiple regimens because of refractory disease, and 11 (65%) of 17 patients underwent autologous stem cell transplant (ASCT). The median OS was 67 months. After a median follow-up of 38 months (range, 3-106 months), only 5 patients achieved complete remission, 5 had persistent disease, and 7 died (2 progressed to plasma cell leukemia and 1 to blastic variant). In summary, IgM PCM is highly associated with t(11;14) and lymphoplasmacytic morphology. Patients are refractory to novel therapy and progression to high-risk myeloma is common, suggesting a need for alternative novel therapies.

CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia.

The potential of CD123-targeted therapies in acute lymphoblastic leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with acute lymphoblastic leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B acute lymphoblastic leukemia/lymphoma cell lines and primary B acute lymphoblastic leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B acute lymphoblastic leukemia/lymphoma and 30 with T acute lymphoblastic leukemia/lymphoma. CD123 expression was more prevalent in B acute lymphoblastic leukemia/lymphoma than in T acute lymphoblastic leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P<0.0001), and within B acute lymphoblastic leukemia/lymphoma CD123 expression was more prevalent in Philadelphia chromosome-positive patients than in Philadelphia chromosome-negative patients (96.6% versus 86.3%; P=0.033). In T acute lymphoblastic leukemia/lymphoma, 12/13 (92.3%) patients with CD123-positive blasts had either early T precursor (ETP) or early non-ETP immunophenotype. IMGN632 was highly cytotoxic to B acute lymphoblastic leukemia/lymphoma cell lines, with half maximal inhibitory concentrations (IC50) between 0.6 and 20 pM. In five of eight patients' samples, low picomolar concentrations of IMGN632 eliminated more than 90% of the B acute lymphoblastic leukemia/lymphoma blast population, sparing normal lymphocytes. In conclusion, CD123 expression is prevalent across acute lymphoblastic leukemia/lymphoma subtypes, and the CD123-targeted antibody-drug conjugate IMGN632 demonstrates promising selective activity in preclinical models of B acute lymphoblastic leukemia/lymphoma.

Clinicopathologic and molecular features in hairy cell leukemia-variant: single institutional experience.

Hairy cell leukemia-variant is rare. Only a small number of cases have been reported in the literature with little cytogenetic or molecular data available. In this study, we describe the clinicopathologic and genetic features of 23 patients with hairy cell leukemia-variant (16 men and 7 women) with a median age of 70 years. Most patients had splenomegaly (90%), leukocytosis (77%), and lymphocytosis (82%); no patients had monocytopenia. Histologically, the bone marrow biopsy specimens showed a mixed pattern of predominantly interstitial and lesser intrasinusoidal infiltration by leukemic cells. In bone marrow aspirate smears most cells had villous cytoplasmic features and a small nucleolus. We describe unusual sites of hairy cell leukemia-variant involvement in 4 patients, including brain, omentum, terminal ileum, and skin at the time of initial presentation. Immunophenotyping showed monotypic B-cells positive for pan B-cell antigens, CD11c, and CD103, and negative for CD25 and annexin A1. Conventional cytogenetic or fluorescence in situ hybridization analysis showed deletions of 17p13/TP53 and 11q22/ATM gene in 5/12 (42%) and 2/9 (22%) cases, respectively. Sequencing of the variable region of IGVH showed mutations (>2% deviation from germline) in 40% of the cases assessed. MAP2K1 mutation (p.C121S) was seen in 1 of 14 (7%) patients tested. No BRAF V600E mutations were detected. The patients were treated in a heterogeneous manner, but most often with therapies designed for classical hairy cell leukemia and the 5-year overall survival was 84%. In summary, hairy cell leukemia-variant exhibits a heterogeneous spectrum of clinical, morphologic, immunophenotypic, and genetic features that may overlap with classic hairy cell leukemia and other hairy cell-like B-cell neoplasms. A subset of patients can have an aggressive clinical course. In our experience MAP2K1 mutations are uncommon in this disease.

Plasma asymmetric dimethylarginine levels in healthy people.

UNLABELLED: Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of the endothelial nitric oxide synthase (eNOs). ADMA is believed to be implicated in angiogenesis because it regulates the nitric oxide biosynthesis; any pathological abnormalities in ADMA play a crucial role in the pathogenesis and progression of atherosclerosis. The AIM of the present study was to determine the reference range for plasma concentration of ADMA in a sample of Bulgarian population. PATIENTS AND METHODS: To establish the reference interval of ADMA plasma levels and study the impact of sex and age we recruited 150 healthy subjects of Bulgarian nationality aged between 18 and 65 years. The selection criteria for the reference group were made to comply with the generally approved recommendations of the International Federation of Clinical Chemistry (IFCC). Plasma concentrations of ADMA were determined using ELISA assay (DLD, Diagnostics, Hamburg, Germany). RESULTS: The reference ranges for ADMA, given as 95% of the measured values, were from 0.22 to 0.69 micromol/1. We found no sex-related differences in ADMA concentration (P > 0.05), which obviates the need for separate reference intervals for men and women. Single-factor dispersion analysis found no age dependency ofADMA (P > 0.05, F = 1.038) in the studied reference group in the age range 18-65 which makes unnecessary establishment of reference intervals for lower age ranges in this age group. CONCLUSION: The reference values for ADMA plasma concentrations calculated according to the type of distribution of results can be used as baseline criteria in clinical laboratory studies and for clinical purposes.

Associations between serum selenium and total plasma homocysteine during the acute phase of ischaemic stroke.

BACKGROUND/AIMS: Risk of ischaemic stroke (IS) was associated with total homocysteine (tHCY). On the other hand, serum selenium (Se) exhibited anti-aging and cardiopreventive effects. Se and tHCY showed relationships in animals but these were contradictory or inconclusive in humans; therefore, we searched for such associations in acute IS. METHODS: Ninety-four participants aged around 47 years were identified and 39 patients versus 46 healthy controls were analysed. Clinical, laboratory (blinded) and risk factor questionnaire methods were used. Comparison, correlation and multifactorial regression analyses were applied. RESULTS: IS patients were similar to controls concerning age and gender. IS was prevalent in the carotid system (76.9%); 82.1% had a subacute onset. IS patients expressed higher tHCY (14.65 +/- 9.79 micromol/l) and lower Se levels (1.3 +/- 0.5 micromol/l). Twice as many IS patients (23%) had optimal Se levels of <1.01 mumol/l. Subjects with hyperhomocysteinaemia (tHCY > or =15 micromol/l) showed lower Se levels during IS; Se accounted for 15.4% of tHCY variations (R = -0.393; p = 0.015) with unit change increasing tHCY by 8.25 units. Se remained predictive of tHCY levels after adjustments (vitamin B6, fibrinogen, triglycerides). CONCLUSIONS: Lower Se was observed during acute IS, being inversely associated with and predicting increased tHCY levels. Of note, there were more IS patients with suboptimal Se than controls.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients.

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased normal homocysteinaemia, i.e., hidden (pathologically dormant) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001). An increase of THCY with 1.0 micromol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 micromol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68%) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients

BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS). However, especially in young adults, there is possibility of significantly increased IS risk due to increased ænormalÆ homocysteinaemia, i.e., æhiddenÆ (æpathologically dormantÆ) prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY) in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL). At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72 percent model accuracy, p model=0.001). An increase of THCY with 1.0 æmol/L was associated with 22 percent higher risk of ischaemic stroke [adjusted OR=1.22 (95 percentCI 1.03?1.44)]. In this way, novel lower cut-off value for HCY of 11.58 æmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI percent 0.55-0.78, p=0.009). CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63 percent, specificity>68 percent) irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.

OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular cerebral isquêmico (AVCI). Todavia, em adultos jovens existe a possibilidade de aumento significativo de risco de AVCI devido a aumento "normal" da homocisteinemia, "oculta" (patologicamente adormecida) dentro de uma variação definida como normal. Neste trabalho foi investigado um modelo post-hoc de dosagem de homocisteina no plasma (HC) em pacientes jovens com AVCI agudo pareados por gênero e idade. Foi avaliado também relações entre HC e prevalência de outros fatores de risco para AVCI em 41 pacientes e 41 controles normais. MÉTODO: Foi utilizado exame clínico, procedimentos instrumentais e de neuroimagem, exame de fatores de risco, dosagem da homocisteína no plasma, outros exames laboratoriais e análise estatística. RESULTADOS: Não foram encontradas diferenças quanto a presença de fumantes, dosagem de vitaminas, creatinina sérica e perfil lipídico entre os pacientes com AVCI e os controles normais. Todavia os pacientes com AVCI apresentaram diminuição de níveis de vitamina B6 e aumento de homocisteína, fibrinogênio e trigliceridios. A análise multivariada de regressão logística mostrou diferenças significativas apenas para HC e trigliceridios independentemente associadas para fatores de risco para AVCI (72 por cento acuracia, p= 0,001). Um aumento de homocisteína de 1,0 æmol/L estava associado com aumento de 22 por cento de risco de AVCI [OR=1,22 (95 por centoIC 1,03-1,44)]. Foi evidenciado portanto um novo valor de cut-off para HC de 11,58 æmol/L em pacientes jovens com AVCI (ROC auc=0,67, 95 por cento IC 0,55-0,78, p= 0,009). CONCLUSÃO: Este novo valor de cut-offpara a homocisteína discrimina claramente a ausência ou presença de AVCI (sensibilidade >63 por cento, especificidade >68 por cento) independente do gênero ou idade e deve ser aplicado para uma melhor avaliação precoce de pacientes jovens com risco de AVCI.

Total plasma homocysteine in Bulgarian population measured by high-performance liquid chromatography with fluorescence detection--comparison with fluorescence polarization immunoassay.

Over the last decade, evidence has accumulated that elevated total homocysteine (tHcy) is an independent risk factor for vascular disease. Due to the variety of Hcy determinants (age, gender, ethnicity and lifestyle), it is now recommended that the distribution of plasma Hcy concentrations should be established for different populations. Therefore the objective of our study was to evaluate a modified HPLC with fluorescence detection procedure for reliable quantification of tHcy and to demonstrate its successful application to determine the distribution of tHcy levels in healthy Bulgarians. The presented method showed good analytical performance (intra- and interassay CVs were <3.9% and <6.7%, respectively; inaccuracy was <6.5%, and analytical recovery 95%-98%, the detection limit was 0.3 micromol/l) and no drug interference was registered. Comparison between HPLC-FD and FPIA using Passing-Bablok regression analysis (r=0.9906) showed good agreement. We describe the distribution of plasma tHcy in a group of 162 healthy Bulgarian adults and examined its relation with age and gender. Our results indicate that higher Hcy concentrations were associated with male sex and increasing age. The higher plasma Hcy observed in our population compared to the rest of Europe corresponds to the high prevalence and mortality of cardiovascular disease in Bulgaria.

A study of plasma total homocysteine levels in healthy people.

UNLABELLED: Elevated plasma levels of homocysteine have been identified as an independent risk factor for atherosclerosis. AIM: The aim of this study was to determine the reference limits of plasma total homocysteine for Bulgarian population. MATERIALS AND METHODS: We investigated 153 healthy individuals without vitamin deficiency aged from 18 to 65 years. The reference group consisted of 74 males and 79 females with mean age respectively 37.80 +/- 1.36 and 39.32 +/- 1.33 years. Plasma total homocysteine was determined by high performance liquid-chromatography (HPLC) modified and validated in our laboratory. RESULTS: The reference intervals were 7.4-18.5 micromol/l for males and 5.5-14.5 micromol/ 1 for females. The mean levels of plasma homocysteine were significantly higher in males in comparison with females (11.86 +/- 0.33 micromol/l vs. 9.88 +/- 0.27 micromol/l; P < 0.001), without considerable correlation with age. Comparing the values of total homocysteine between the two groups of age - < or = 49 and > or = 50 years showed that the investigated individuals > or = 50 years had higher plasma concentration, and the difference was significant only for the group of females. Hyperhomocysteinemia according to ECAP cut-off value (> 12.1 micromol/l) was registered in 30.7% of healthy volunteers. CONCLUSIONS: The results of our study demonstrated that homocysteine levels depend on sex and, to a lesser degree, on age. We have determined plasma total homocysteine reference intervals for the Bulgarian population. This will help the interpretation of the results and contribute to adequate and efficient prevention of blood vessel diseases.