Prolonged breastfeeding and protective effects against the development of allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: There is insufficient evidence to confirm the protective effects of prolonged breastfeeding against the development of allergic rhinitis (AR). METHODOLOGY: A systematic review and meta-analysis was performed to assess the associations between prolonged breastfeeding and AR symptoms later in life. Comparisons were conducted between breastfeeding durations less than 6 months and 6 months or more and between less than 12 months and 12 months or more. Exclusive breastfeeding and nonexclusive breastfeeding were analysed separately. Outcomes were risks of AR development later in life. RESULTS: Twenty-three observational studies (161,611 children, age 2-18 years, 51.50% male) were included. Two studies (9%) were with high quality. Both exclusive and nonexclusive prolonged breastfeeding (6 months or more) decreased the risk of AR. The long-term (12 months or more) nonexclusive breastfeeding lowered the likelihood of AR compared to the 12 months or fewer. The long-term exclusive breastfeeding did not show the same protective effect; however, this result was restricted to only one study. CONCLUSIONS: Exclusive breastfeeding and nonexclusive breastfeeding for 6 months or more may have protective effects against the development of AR up to 18 years of age. The findings should be interpreted with caution given the limitation of low-quality observational studies.

As-needed intranasal corticosteroid spray for allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: As-needed intranasal corticosteroid spray (INCS) is commonly used by patients with allergic rhinitis (AR) who have suboptimal symptom control. This systematic review aimed to assess the effectiveness of as-needed INCS for treating AR. METHODOLOGY: Systematic searches for randomized controlled trials studying the effects of as-needed INCS compared to regular INCS, as-needed antihistamine, or placebo were performed. Primary outcomes were total nasal symptom score (TNSS) and disease-specific quality of life (DSQoL). RESULTS: Eight studies (882 participants) met the criteria. Regular use of INCS showed greater improvements than as-needed INCS in TNSS, DSQoL, nasal peak inspiratory flow, sneezing, and nasal congestion scores with small effect sizes. There were no differences between regular and as-needed INCS usage for ocular symptoms, symptom-free days, nasal itching, and rhinorrhea scores. As-needed INCS was superior to as-needed antihistamine and placebo with medium effect sizes. There were no differences in risk of adverse events between the groups in all three comparisons. CONCLUSIONS: Regular use of INCS improved total nasal symptoms score and DSQoL better than as-needed INCS. However, as-needed INCS improved TNSS better than as-needed antihistamine and placebo. The effects of as-needed INCS were closer to regular INCS usage than to placebo or as-needed AH usage.

Allergen-specific immunotherapy for local allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of chronic rhinitis exhibiting a local Th2-driven inflammation without positive clinical markers of atopy. Immunomodulatory effects of allergen-specific immunotherapy (AIT) induce allergen-specific tolerance. However, AIT is not well-recognized as a treatment for LAR. METHODOLOGY: Systematic search on six electronic databases and registries was performed. Experimental and observational studies of AIT for LAR patients were retrieved. The primary outcomes were symptom score, medication score, combined symptom medication score, and disease-specific quality of life. Secondary outcomes were serum specific(s) IgG4, sIgE, and adverse events. RESULTS: Four double-blind randomized controlled trials (156 patients) from two research units assessed the effects of subcutaneous immunotherapy (SCIT). Compared with placebo, SCIT showed significant reductions in symptom score, medication score, combined symptom medication score, disease-specific quality of life, and an increase in serum sIgG4. There was no significant change in serum sIgE. Likewise, two observational studies (one using SCIT and one using sublingual immunotherapy) improved post-therapeutic symptom score. No studies assessed the effects after discontinuation of treatment. AIT was safe without serious adverse events. CONCLUSION: AIT has beneficial effects and safe for LAR. Its effects are restricted to studies with short-term follow-up. AIT may be considered in LAR patients.

Intralymphatic immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta-analysis.

BACKGROUND: Intralymphatic immunotherapy (ILIT) is a new route of allergen-specific immunotherapy. Data confirming its effect is restricted to a small number of studies. METHODOLOGY: A systematic review with meta-analysis was conducted. The short-term (less than 24 weeks), medium-term (24-52 weeks), and long-term (more than 52 weeks) effects of ILIT in patients with allergic rhinoconjunctivitis (ARC) were assessed. The outcomes were combined symptom and medication scores (CSMS), symptoms visual analog scale (VAS), disease-specific quality of life (QOL), specific IgG4 level, specific IgE level, and adverse events. RESULTS: Eleven randomized controlled trials and 2 cohorts (483 participants) were included. Compared with placebo, short term benefits of ILIT for seasonal ARC improved CSMS, improved VAS and increased specific IgG4 level but did not change QOL or specific IgE level. Medium-term effect improved VAS. Data on the long-term benefit of ILIT remain unavailable and require longer term follow-up studies. There were no clinical benefits of ILIT for perennial ARC. ILIT was safe and well-tolerated. CONCLUSION: ILIT showed short-term benefits for seasonal ARC. The sustained effects of ILIT were inconclusive. It was well tolerated.

KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas.

BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.

Stem cell markers (cytokeratin 15, CD34 and nestin) in primary scarring and nonscarring alopecia.

BACKGROUND: Although the pathogenesis of most primary scarring alopecias is poorly understood, recent studies implicate the bulge region as a possible target. OBJECTIVES: To corroborate these results, we ascertained involvement of follicular bulge stem cells using a panel of antibodies that putatively targeted the same. METHODS: Antibodies used included anticytokeratin (CK) 15, CD34 and nestin on vertical and horizontal tissue sections of 50 cases of scarring and 34 cases of nonscarring alopecia. RESULTS: Comparing expression of these markers in scarring vs. nonscarring alopecia, CK15 was noted in the follicular bulge region in 23 of 43 (53%) vs. 27 of 27 (100%) cases and in the peripheral layer of the outer root sheath (ORS) (upper two-thirds of the follicle) in 50 of 50 (100%) vs. 34 of 34 (100%) cases; CD34 was noted in the peripheral layer of the ORS (below pilar muscle attachment) in 24 of 35 (69%) vs. 18 of 18 (100%) cases; and nestin was noted in the infundibular region in 18 of 46 (39%) vs. seven of 32 (22%) cases and in the inner aspect of the ORS (below pilar muscle attachment) in eight of 31 (26%) vs. 23 of 23 (100%) cases. CONCLUSIONS: Our findings of differential follicular localization of stem cells underscore follicular progenitor cell heterogeneity and suggest the target in scarring alopecia is not merely follicular bulge stem cells but involves stem cells in the inner and outer aspect of the ORS. Enhanced expression of nestin in the infundibular region in scarring alopecia indicates availability of an accessible, in vivo niche of potential utility as an autologous source of stem cells for therapeutic application.

Histologic spectrum of arterial and arteriolar lesions in acute and chronic cocaine-induced mesenteric ischemia: report of three cases and literature review.

Gastrointestinal complications of cocaine abuse occur less frequently than those of the cardiovascular and nervous systems. The clinical history and pathologic findings of three patients with cocaine-induced mesenteric ischemia are described, and the mechanism of acute and chronic cocaine-induced mesenteric ischemia is discussed. The role of preoperative angiography in detecting occlusive arterial lesions so that arterial revascularization can be carried out is emphasized. Briefly, recent intravenous cocaine use in a 45-year-old man resulted in sharply demarcated small intestinal ischemia with perforation characterized by pseudomembranous enteritis. Histologic sections of the small-bowel resection showed intraluminal fibrin and intimal hyperplasia in rare submucosal arterioles. Two women, 29 and 35 years of age, both with a 2-year history of intravenous cocaine use, presented with acute abdominal pain and had angiographic documentation of occlusion of the celiac axis and the superior mesenteric arteries. Vascular bypasses were performed in both cases. Microscopic examination of both arteries and their branches revealed total obstruction by luminal thrombus with recanalization.

Clear cell endocrine pancreatic tumor mimicking renal cell carcinoma: a distinctive neoplasm of von Hippel-Lindau disease.

The dominantly inherited von Hippel-Lindau disease is characterized by clear cell neoplasms in various organs including the kidney and pancreas. Determination of primary versus metastatic lesion in this setting can be a diagnostic dilemma. The authors present five cases of clear cell endocrine pancreatic tumor (EPT) closely mimicking renal cell carcinomas in five patients with a family history or histologic evidence of von Hippel-Lindau disease. In fact, two of these tumors were confused with metastatic renal cell carcinoma by fine-needle aspiration. All five tumors had a component of clear cells arranged in nests, cords, and tubules with central hemorrhage separated by thin-wall vessels resembling renal cell carcinoma. However, these tumors also exhibited cords and festoons and a gyriform pattern suggestive of an endocrine neoplasm, and expressed chromogranin and synaptophysin. Vascular invasion was identified in four tumors, one of which metastasized. The concurrent primary renal cell carcinomas and the multicentric microcystic adenomas found in three patients did not show reactivity for the neuroendocrine markers. Focal clear cell change was noted in only one of 29 endocrine pancreatic tumors arising in patients without von Hippel-Lindau disease. Eleven metastatic renal cell carcinomas in the pancreas did not show immunoreactivity with the endocrine markers. Clear cell EPTs closely mimicking renal cell carcinoma are distinctive neoplasms of von Hippel-Lindau disease. In contrast to clear cell EPT, metastatic renal cell carcinoma does not express neuroendocrine markers and lacks neurosecretory granules by electron microscopy. Von Hippel-Lindau disease should be strongly suspected in patients with renal cell carcinoma, clear cell EPT, and multifocal microcystic serous adenomas.

Clear cell carcinoid tumor of the gallbladder: another distinctive manifestation of von Hippel-Lindau disease.

We describe a morphologically distinctive carcinoid tumor of the gallbladder that occurred in a 38-year-old man with von Hippel-Lindau (VHL) disease. The carcinoid tumor was composed predominantly of lipid-containing clear cells arranged in nests and tubules with pagetoid spread into the biliary epithelium and was interpreted as metastatic renal cell carcinoma. The neoplastic cells showed diffuse immunoreactivity for chromogranin, synaptophysin, cytokeratins (cytokeratin 7 and AE1/AE3) and, unexpectedly, for inhibin, but were negative for monoclonal carcinoembryonic antigen, serotonin and a variety of peptide hormones. This clear cell carcinoid tumor of the gallbladder was histologically similar to the recently described clear cell endocrine pancreatic tumor associated with VHL. Four cases of the latter tumor, which were also inhibin positive showed, in addition, focal and variable reactivity for the pancreatic hormones. Two classical carcinoid tumors of the gallbladder, two renal cell carcinomas associated with VHL and 11 of 13 sporadic endocrine pancreatic tumors (not associated with VHL) did not show immunoreactivity for inhibin. Inhibin appears to be an immunohistochemical marker for gallbladder clear cell carcinoid and clear cell endocrine pancreatic tumors associated with VHL and is a useful tool to distinguish these tumors from metastatic renal cell carcinoma. However, the basis for the inhibin positivity in these endocrine tumors is unknown.

Atypical bile duct adenoma, clear cell type: a previously undescribed tumor of the liver.

A variable proportion of bile duct adenomas of the liver are still confused with metastatic well-differentiated adenocarcinoma by surgeons and pathologists. We present here three examples of previously undescribed primary hepatic bile duct tumors that were composed almost entirely of clear cells that closely mimicked metastatic renal cell carcinoma. They were interpreted as atypical bile duct adenomas and occurred in two males and one female whose ages ranged from 25 to 64 years. All three tumors were incidental findings and measured from 0.8 to 1.1 cm. The clear neoplastic cells showed mild nuclear atypia and no mitotic activity. They were arranged in tubules and nests that focally infiltrated the hepatic parenchyma. For comparison, a case of clear cell cholangiocarcinoma and 13 conventional bile duct adenomas were examined. The clear cell cholangiocarcinoma was larger (6.0 cm) and had the tubular pattern of conventional cholangiocarcinoma and an abundant desmoplastic stroma. The clear cells of this tumor exhibited greater nuclear atypia and increased mitotic activity. All three atypical bile duct adenomas expressed cytokeratin (CK) 7, p53 protein, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA); they were negative for CK20, vimentin, Hep Par 1, chromogranin, and prostatic specific antigen (PSA) and exhibited less than 10% of Ki-67-positive nuclei. One atypical bile duct adenoma displayed luminal immunoreactivity for villin. With the exception of Ki-67 reactivity, the 13 conventional bile duct adenomas and the clear cell cholangiocarcinoma had essentially a similar immunohistochemical profile as that of the atypical clear cell bile duct adenomas. The absence of an extrahepatic primary tumor, the histologic features, the immunohistochemical profile, and the fact that all patients are symptom-free 2 months to 18 years after wedge liver biopsy support the interpretation of atypical clear cell bile duct adenoma. The differential diagnosis with clear cell hepatocellular carcinoma and metastatic clear cell carcinomas is discussed.

Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma.

Salivary duct carcinoma (SDC) is a rare high-grade aggressive neoplasm that manifests close histologic features with invasive ductal carcinoma of the breast (IDC). In contrast to SDC, extensive molecular studies have been performed on IDC and led to the identification of certain biological markers. To investigate the underlying molecular and biologic characteristics of SDC, we performed molecular analyses using microsatellite markers on chromosomal arms 6q, 16q, 17p, and 17q, DNA flow cytometry and immunohistochemical staining for androgen receptor (AR) and p53 expression on 28 examples of these tumors in comparison to 24 IDC cases. Our results show that generally similar allelic alterations, elevated p53 and androgen receptor expressions, and high frequency of DNA aneuploidy are manifested in both SDCs and IDCs. Differences at certain markers on 6q, 17p and 17q chromosomal loci, however, were observed between the two entities. Certain loci on 6q were more frequently altered in SDC than IDC which loci on chromosomes 17p and q arms were more seen in IDCs than SDCs. The majority of SDCs had high AR expression while most of IDCs were AR negative. Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.

Primary mammary small-cell carcinoma: a molecular analysis of 2 cases.

Primary small-cell carcinoma of the breast is an exceedingly rare variant of breast carcinoma whose genetic profile has not been previously investigated. We report the molecular features of 2 cases of small-cell carcinoma of the breast: 1 with an adjacent intraductal carcinoma, and 1 with prior pleomorphic lobular carcinoma in situ. Laser capture microdissection followed by loss of heterozygosity (LOH) analysis revealed identical molecular alterations at multiple chromosomal regions, including BRCA-1, BRCA-2, p53, and retinoblastoma gene loci, in 1 case of small-cell carcinoma and its adjacent intraductal component. Additionally, LOH in 1 or both small-cell carcinomas was detected at 3p, 4q31.2-qter, 8p21-24, 11q13 (MEN-1 locus), 11q23.3, 11q24.1-25, 16q24.1 (H-cadherin locus), and 17q25. The results of our molecular analysis suggest that genetic changes in mammary small-cell carcinoma resembled those seen in both invasive ductal carcinomas and pulmonary small-cell carcinoma. Second, mammary small-cell carcinoma is clonally related to ductal carcinoma in situ and might represent an example of divergent differentiation occurring in a multipotential neoplastic stem cell.

Polymerase chain reaction amplification of archival material for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, and parvovirus B19 in children with bone marrow hemophagocytosis.

Bone marrow hemophagocytosis may occur as an incidental finding, or it may be a manifestation of a systemic and potentially lethal disorder. When systemic, the proliferation is termed hemophagocytic lymphohistiocytosis (HLH), a clinicopathologic entity characterized by a widespread proliferation of benign hemophagocytic histiocytes, fever, pancytopenia, deranged liver function, and frequently coagulopathy and hepatosplenomegaly. A variety of infectious agents, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), and parvovirus B19 (PVB19), have been associated with HLH, but the relative frequency of each using one technique has not been evaluated. In addition, infectious causes of incidental bone marrow hemophagocytosis, not occurring in the setting of HLH, have not been evaluated. Review of bone marrow reports from bone marrow examinations done between December 1986 and June 1997 showed that 20 children aged 2 months to 15 years had bone marrow examinations that indicated hemophagocytosis. Archival materials from 19 patients were successfully retrieved, and DNA was extracted from archived unstained coverslips with subsequent polymerase chain reaction for EBV, CMV, HHV6, and PVB19 genomic DNA. DNA extracted from 16 bone marrow specimens of age-matched children was used as negative controls. Eleven of the 19 patients fulfilled the clinical and pathological criteria for HLH; the remaining eight patients had isolated hemophagocytosis without a systemic presentation. Viral DNA was detected in 8 of 11 patients with HLH but in none of eight patients with isolated hemophagocytosis. EBV was present in five of the bone marrows, followed in frequency by HHV6, CMV, and PVB19. Infection with more than one agent was present in three patients. Only one control patient was positive for HHV6 DNA; the remaining control patients were negative for all viruses. Viral infection, detected by PCR analysis of bone marrow, is a common finding in patients with HLH but not in patients with isolated bone marrow hemophagocytosis. This technique may provide another marker to aid in the diagnosis of HLH and suggests a different cause of hemophagocytosis occurring in patients with and without HLH.

HER-2/neu gene amplification compared with HER-2/neu protein overexpression and interobserver reproducibility in invasive breast carcinoma.

We compared the detection of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH) with detection of HER-2/neu protein overexpression by immunohistochemistry using 2 antibodies on 100 archival invasive breast carcinomas. Protein overexpression for each marker was scored independently by 4 pathologists using standardized criteria, and consensus was compared with results obtained from gene amplification. The concordance rate between FISH and immunohistochemistry was 76% for e2-4001 and 91% for the HercepTest. Of the 37 cases positive by e2-4001, 21 demonstrated no gene amplification; 7 of 24 cases positive by the HercepTest demonstrated no gene amplification. However, 1 of 61 cases negative by e2-4001 showed gene amplification; none of the cases negative by the HercepTest showed amplification. The predictive values of gene amplification based on 0-1+, 2+, and 3+ immunohistochemical staining were best for cases scored as 3+ (75% for e2-4001 and 89% for the HercepTest). Complete agreement among observers for immunohistochemical scoring of e2-4001 and the HercepTest was achieved in 75 and 85 cases, respectively. The pairwise kappa agreement values were substantial for e2-4001 and substantial to almost perfect for the HercepTest. Immunohistochemical staining may be considered a useful screening test. While negative staining almost always correlated with a lack of gene amplification, positive membranous staining, especially 2+, did not predict gene amplification. The low interobserver reproducibility in separating 2+ from 3+ cases necessitates further confirmation by FISH before treatment decisions are made.

Quantitation of 8 human herpesviruses in peripheral blood of human immunodeficiency virus-infected patients and healthy blood donors by polymerase chain reaction.

Human herpesviruses are associated with morbidity and mortality in persons with compromised immune systems, including patients infected with human immunodeficiency virus (HIV). To investigate the basis for this association, the levels of all 8 human herpesviruses (herpes simplex virus, types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6, human herpesvirus 7, and human herpesvirus 8) were measured with the quantitative polymerase chain reaction (PCR). Viral DNA was measured in the whole blood of 20 HIV-infected patients and compared with levels in 20 healthy blood donors. There was no significant difference in the frequency of virus detection of the 8 human herpesviruses between HIV-infected patients and healthy adults. These results indicate that HIV infection is not associated with a general increase in the circulating levels of human herpesviruses, and suggest that quantitative PCR analysis is superior to qualitative PCR analysis for detection of clinically relevant disease in HIV-infected patients.

Bisalbuminuria in an adult with bisalbuminemia and nephrotic syndrome.

Bisalbuminemia (or alloalbuminemia) is a relatively rare hereditary or acquired condition characterized by the presence of two distinct albumin bands, or, less commonly, a single widened albumin band, after agarose gel electrophoresis of serum. Bisalbumins are caused by point- or chain-mutations that occur with a population frequency of 1:10,000 to 1:1000. Although no adverse clinical effects have been attributed to bisalbumins, some albumin variants have altered affinity for steroid hormones, thyroxine, or drugs. We report a case of bisalbuminuria in a 25-year-old man with bisalbuminemia and nephrotic syndrome.

Expression of protein gene product 9.5 in epithelioid and conventional malignant peripheral nerve sheath tumors.

CONTEXT: Due to the frequent lack of S100 protein expression in malignant peripheral nerve sheath tumors (MPNSTs), especially the epithelioid variant, these tumors are difficult to diagnose without the aid of electron microscopy or a clinical history of neurofibromatosis. METHODS: Protein gene product 9.5 (PGP9.5), a broad neural marker, is expressed in nerve fibers and neurons of both the peripheral and central nervous systems. We compared its expression to that of S100 protein in 16 cases of MPNST. As controls, 6 monophasic synovial sarcomas, 9 leiomyosarcomas, and 5 dermatofibrosarcoma protuberans were included. RESULTS: Expression of PGP9.5 was seen in 15 MPNSTs, with 3 to 4+ positivity in the majority of the cases. Ten cases, 2 epithelioid and 8 conventional MPNSTs, were reactive with PGP9.5, but were negative for S100 protein. Five cases were immunoreactive for both S100 protein and PGP9.5. One case was negative for PGP9.5 but demonstrated focal S100 protein positivity. Expression of PGP9.5 was seen in 4 of 6 synovial sarcomas, 3 of 9 leiomyosarcomas, and none of 5 dermatofibrosarcoma protuberans. CONCLUSION: Although PGP9.5 is not a specific marker for MPNST, it is a more sensitive marker than S100 protein (94% vs 38%). When there is a lack of S100 protein expression and a broad panel of immunostains, such as cytokeratin, epithelial membrane antigen, and smooth muscle actin, yields only focal or equivocal staining, PGP9.5 is a useful diagnostic adjunct in confirming the neural origin of a spindle cell sarcoma.

Comparison of 2 homogeneous high-density lipoprotein cholesterol assays.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is an independent inverse risk factor for coronary artery disease. Current methodologies for measurement of HDL-C in most clinical laboratories involve chemical precipitation-based methods. However, these methods are time-consuming, affected by high triglycerides, are not suitable for complete automation, and require a large sample size. New direct homogeneous methods are now available that do not have these constraints. DESIGN: We evaluated the performance of 2 direct homogeneous methods, Liquid N-geneous HDL-C assay (LN-HDL) and Boehringer Mannheim HDL Cholesterol assay (BM-HDL), and compared these methods against a modified Centers for Disease Control and Prevention reference method (MR-HDL) in 126 patients with normotriglyceridemia (triglycerides < 4.5 mmol/L, range 0.6-4.3 mmol/ L) and 50 patients with hypertriglyceridemia (triglycerides > or =4.5 mmol/L, range 4.5-18.8 mmol/L). RESULTS: Excellent precision profiles were exhibited by both homogeneous methods. Both LN-HDL and BM-HDL correlated well with MR-HDL in normotriglyceridemia (r = 0.98, slope = 0.93 and r = 0.97, slope = 1.0, respectively). However, compared with the modified reference method, the LN-HDL correlated better than the BM-HDL in hypertriglyceridemic samples (r = 0.97, slope = 1.0 and r = 0.91, slope = 0.9, respectively). The 1998 National Cholesterol Education Program guidelines for accuracy (bias < +/-5%) were met by LN-HDL in both normotriglyceridemic and hypertriglyceridemic samples (bias = 1.3% and 3.3%, respectively); however, BM-HDL failed to meet the National Cholesterol Education Program accuracy criteria in both triglyceride subgroups (bias = 8.2% and 11.3%, respectively). In addition, the total error for LN-HDL in both normotriglyceridemia (6.6%) and hypertriglyceridemia (8.6%) was well within the National Cholesterol Education Program guidelines for total error (< or =13%); BM-HDL exhibited a higher total error than LN-HDL in normotriglyceridemia (11.9%) and failed to meet the National Cholesterol Education Program guidelines in hypertriglyceridemia (15.0%). CONCLUSION: Although both homogeneous methods are precise, the LN-HDL assay is superior in accuracy to the BM-HDL assay when compared with the modified reference method.