Atherogenic changes in low-density lipoprotein particle profiles were not observed in non-obese women with polycystic ovary syndrome.

STUDY QUESTION: Is a preponderance of small dense low-density lipoprotein-cholesterol (LDL-C) observed in non-obese women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Non-obese Korean women with PCOS have no quantitative or qualitative changes in LDL-C profiles. WHAT IS KNOWN ALREADY: Small dense LDL particles (sd-LDL) are more atherogenic than large buoyant ones and are strongly associated with coronary artery disease independent of other risk factors. Many investigators have found an increased proportion of atherogenic sd-LDL or a decreased mean LDL particle size in women with PCOS, but all of these studies have been based primarily on obese or overweight women with PCOS. STUDY DESIGN, SIZE, DURATION: This was a case-control study evaluating complete lipid and lipoprotein profiles in 64 PCOS patients and 64 age- and BMI-matched controls. All women with PCOS in our study population were not obese. To determine the differences in the LDL particle profiles between PCOS phenotypes, the patients with PCOS were divided into two subgroups according to the presence of clinical or biochemical hyperandrogenism. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Rotterdam criteria, we recruited 64 women (18-40 years) with PCOS who were attending a tertiary university hospital. A total of 64 premenopausal control women were matched with patients based on exact age and BMI (± 1.0 kg/m(2)). All the participants fell within the non-obese range of the BMI (<25 kg/m(2)) according to the definition of obesity for Asians. The LDL subfraction was analyzed by 3% polyacrylamide gel tube electrophoresis. Seven LDL subclasses were quantified and LDL subclasses 3-7 were small LDL subfractions. LDL subfraction scores were calculated based on the following weighted scoring system developed by the manufacturer: scores of <5.5 were categorized as phenotype A (large, buoyant LDLs), and those >5.5 were categorized as non-A phenotype (sd-LDLs). The system also determined the mean LDL particle size diameter. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the absolute level of LDL-C, mean LDL diameter or percentage of atherogenic sd-LDLs between PCOS patients and controls or between hyperandrogenic and non-hyperandrogenic PCOS subgroups. Also, none of the subjects showed a non-A LDL phenotype. The most notable finding of our study was the difference in the lipoprotein (a) levels and prevalence of its elevation in PCOS patients versus controls (P = 0.002 and P = 0.004, respectively), and between PCOS subgroups (P = 0.030 and P = 0.047, respectively). LIMITATIONS, REASONS FOR CAUTION: Inclusion of only non-obese subjects, small sample size and lack of information on other potential confounding factors, such as differences in diet and/or exercise patterns. WIDER IMPLICATIONS OF THE FINDINGS: Although our findings suggest that non-obese women with PCOS have no significant quantitative or qualitative changes in LDL-C profile, data on obese Korean women with PCOS could offer complementary findings about the possible relationship between the magnitude of obesity and LDL phenotype. Further investigations are needed to determine whether a change in lipoprotein (a) in non-obese women with PCOS is also found in other ethnic groups. STUDY FUNDING/COMPETING INTEREST(S): No conflict of interest exists. This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A100624). TRIAL REGISTRATION NUMBER: N/A.

Association of the interferon-γ gene (CA)n repeat polymorphism with endometriosis.

OBJECTIVE: To investigate whether the interferon-γ (IFN-γ) gene (CA)(n) repeat polymorphism is associated with susceptibility to endometriosis. DESIGN: Case-control study. SETTING: University Department of Obstetrics and Gynaecology. POPULATION: Women with (n = 622) and without (n = 442) endometriosis. METHODS: Genotyping was performed by fluorescent polymerase chain reaction (PCR) and gene-scan analysis. MAIN OUTCOME MEASURES: Genotype distribution and allele frequency of the dinucleotide (CA)(n) repeat polymorphism in the IFN-γ gene. RESULTS: Seven alleles (12-18 repeats) of the IFN-γ gene (CA)(n) repeat polymorphism were found. In both patients with endometriosis and controls the most common allele was composed of 13 repeats, followed by an allele of 15 repeats, and then by an allele of 12 repeats. Patients with endometriosis had a significantly higher incidence of genotypes with alleles composed of fewer repeats (12-13 repeats), compared with the controls (92.0 versus 84.4%, respectively, P < 001). CONCLUSIONS: Our results suggest that the (CA)(n) repeat polymorphism in the IFN-γ gene may be associated with a risk of endometriosis in the South Korean population.

Lack of variation in alphaGal expression on lymphocytes in miniature swine of different genotypes.

BACKGROUND: Gal(alpha)1-3Gal epitopes (alphaGal) have been demonstrated to be present on tissues of all pig breeds tested to-date and are the major target for human anti-(alpha)galactosyl (alphaGal) antibodies. We investigated members of an MHC-inbred miniature swine herd to assess whether there was an association between genotype and expression of alphaGal. Identification of a low expressor genotype would potentially enable selective breeding of pigs that might prove beneficial as donors in clinical xenotransplantation. METHODS: we measured alphaGal expression on various pig cells by use of fluorescent-activated cell sorter (FACS) using (i) purified human anti-alphaGal antibody and (ii) the isolectin GS-I-B4. Initial studies were on porcine peripheral blood mononuclear cells (PBMCs) and subsequent studies on lymphocytes, platelets, and T cell subsets (CD4+ and CD8+ cells). RESULTS: there was considerable day-to-day variation in alphaGal expression on PBMCs from the same pig. When only lymphocytes were examined, there was a high degree of reproducibility, and no significant difference in alphaGal expression was detected between representative pairs of animlas of three different genotypes. Purified anti-alphaGal antibody bound to different sites on the alphaGal epitope than did Griffonia (Bandeiraea) simplicifolia I-B4 (GS-I-B4). Lectin binding was significantly reduced in the absence of divalent cations. When CD4+ and CD8+ T cells were examined for alphaGal expression, two distinct populations of each type of cell were observed, with larger cells expressing a higher level of alphaGal. CONCLUSIONS: although the number of pigs of different genotypes studied was small, on the basis of this limited study, pigs of a low alphaGal expressor genotype that could be selectively bred for use in clinical xenotransplantation were not identified.

A clinical consideration of systemic embolism complicated to infective endocarditis in Korea.

OBJECTIVES: Infective endocarditis is still one of the important fatal diseases in Korea, especially when systemic embolisms are supervene. So, identification of patients who are in the high risk of embolism and who can be helped by early surgical intervention is very important. Considering these, we tried to elaborate the risk factors for the systemic embolism in patients with an infective endocarditis and the influence of systemic embolism on the mortality and morbidity in patients with an infective endocarditis. METHODS: We retrospectively reviewed the clinical records of 97 patients who were admitted with the infective endocarditis between January 1983 and October 1993. RESULTS: Among 97 patients, 80 patients met our diagnostic criteria. The mean age of patients was 38 years old. There were 43 males and 37 females. The mean duration of fever since the fever developed by history was 38 days. Valvular heart disease was the most frequent underlying heart disease. Mitral regurgitation and aortic regurgitation were the most common among valvular heart diseases. Pneumonia and acute pharyngotonsillitis were the most frequent predisposing factors of infective endocarditis. Blood cultures were positive in 51 patients (63.8%). Streptococcus viridans was the organism isolated most frequently, and Staphylococcus aureus was the second most frequently isolated one. Vegetations were detected in 58 patients (76.3%) by an echocardiography. Mitral valve and aortic valve were the most frequently involved incidence rate of embolism was 50% and the most frequent embolism site was the central nervous system and extremities were the next. Embolism occurred at the mean of 37 days after onset of fever. Overall in-hospital mortality rate was 26.3% and a cardiac-origin was the major cause of death. The only statistically significant risk factor for mortality was systemic embolism. The analysis of the relation between an incidence of embolism and the multivariables (age, presence of vegetation, location of vegetation, size of vegetation, causative organisms) showed that only the growth of Staphylococcus aureus had a significant trend toward a risk of subsequent systemic embolism. CONCLUSION: This study suggests that systemic emboli increases the mortality rate in patients with infective endocarditis. Age of patients, presence of vegetation, size and location of vegetation are not the risk factors for embolism, while certain organism, especially Staphylococcus aureus, could be a risk factor for the systemic embolism.

Pharmacologic immunosuppressive therapy and extracorporeal immunoadsorption in the suppression of anti-alphaGal antibody in the baboon.

The aim of this study was to deplete baboons of anti-(alpha)galactosyl (alphaGal] antibody and attempt to maintain depletion by pharmacologic immunosuppressive therapy (PI). In 12 experiments, involving nine baboons, repeated extracorporeal immunoadsorption (EIA) was carried out by plasma perfusion through immunoaffinity columns of synthetic alphaGal trisaccharide type 6. Five of the baboons were immunologically naive and four had undergone various procedures at least 6 months previously. All, however, had recovered lymphohematopoietic function and (with one exception) had levels of anti-alphaGal antibody within the normal range. Eleven protocols included continuous i.v. cyclosporine (to maintain whole blood levels of approximately 1,600 ng/ml). In addition, in ten protocols, the baboon received one or more of the following drugs: cyclophosphamide (1-20 mg/kg/day), mycophenolate mofetil (70-700 mg/ kg/day), brequinar sodium (1-12 mg/kg/day), prednisolone (1 mg/kg/day), melphalan (0.15-0.6 mg/kg/day), methylprednisolone (125 mg/day x3), and antilymphocyte globulin (ATG) (50 mg/kg/day x3). EIA was carried out on 1-9 occasions in each study and was temporarily successful in removing all antibody. When no PI was administered, antibody returned close to pre-EIA levels within 48 hr. Cyclosporine alone delayed the rate of antibody return only slightly. While EIA was continuing on a daily or alternate day schedule, antibody levels (both IgM and IgG) were maintained at 20-45% of pre-EIA levels. Once EIA was discontinued but PI maintained, IgM rose to 40-90% and IgG to 30-60% of pre-EIA levels. In vitro testing demonstrated significant cytotoxicity to pig cells at these antibody levels. We conclude that i) EIA utilizing columns of alphaGal trisaccharide is successful in temporarily depleting baboons of anti-alphaGal antibody, but ii) none of the PI regimens tested suppressed antibody production to levels which would be expected to prevent antibody-mediated rejection of pig xenografts. Additional strategies will therefore be required if xenotransplantation is to become a clinical reality.