Changes in survival after transient ischemic attacks: observations comparing the 1970s and 1980s

We compared survival following transient ischemic attack (TIA) in 2 prospective cohorts of TIA patients admitted to Wake Forest University Medical Center. The 1st consisted of 177 patients admitted between 1961 and 1973, and the 2nd of 185 patients admitted between 1980 and 1983. Patients in the 2nd cohort had significantly greater longevity than patients in the 1st cohort, both univariately and after adjustment for cerebrovascular risk factors. The adjusted 1-year survival estimate increased from 91% in the 1st cohort to 98% in the 2nd, and the adjusted 3-year survival estimate increased from 83% in the 1st to 94% in the 2nd. The underlying causes for this dramatic improvement in survival may include early identification and aggressive management of TIAs or coexisting diseases, improved management of subsequent completed strokes or myocardial infarctions, or unadjusted differences in these cohorts. The data imply that reports of TIA survival from different periods may not be comparable.     

Cholesterol distribution in the bulk tissues of man: variation with age

Lacking reliable data on cholesterol concentrations in muscle, adipose tissue, skin, and connective tissues (i.e., the "bulk tissues") in "normal" man, we have completed these analyses in 21 men and 8 women who died suddenly and unexpectedly; their ages ranged from 23 to 78 yr.In 11 of these subjects aged 20-40 yr, the mean cholesterol concentrations ranged from 180-440 mg/100 g dry tissue. In contrast, in 13 subjects aged 60-80 yr the values were 23-28% higher in muscle, adipose, and skin, while in dura mater, biceps, and psoas tendons the concentrations were 130, 260, and 460% higher (respectively). Esterified cholesterol in these connective tissues was found to be the major contributor, increasing 5- to 10-fold in the older group as opposed to a less than 5-fold rise in free cholesterol.In view of the large proportion of total body weight represented by these tissues, it is clear that large amounts of cholesterol can be accumulated there over a lifetime; indeed, the dense connective tissues appear to act uniquely as a trap for cholesterol, especially in the esterified form. Whether analyses of tendinous tissues in man, accessible during life, mirror the pattern of cholesterol deposition in arterial connective tissue remains to be determined.     

Generation and characterization of monoclonal antibodies to human keratinocyte growth factor receptor

Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot analyses. Antagonistic MAbs were identified using a cell-based functional assay. These KGFR MAbs will be important reagents for studying the biological function and tissue distribution of this receptor in normal and pathological conditions.     

Factors associated with presence and extent of coronary calcium in those predicted to be at low risk according to Framingham risk score (from the Multi-Ethnic Study of Atherosclerosis)

Even among asymptomatic persons at low risk (<10%) according to the Framingham risk score, high coronary artery calcium (CAC) scores signify a greater predicted risk of coronary heart disease events. We sought to determine the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 participants from the Multi-Ethnic Study of Atherosclerosis at a low 10-year predicted risk (Framingham risk score <10%) of coronary heart disease events. Multivariate logistic regression analysis was used to assess the association of novel markers with the presence of any CAC (CAC >0) and advanced CAC (CAC ≥ 300). A CAC level of >0 and of ≥ 300 was present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen, and soluble intercellular adhesion molecule were each associated with the presence of CAC (p ≤ 0.02), and C-reactive protein, D-dimer, and the carotid intima-media thickness with advanced CAC (p ≤ 0.03). The base model combining the traditional risk factors had excellent discrimination for advanced CAC (C-statistic 0.808). The addition of the 2 best-fit models combining the biomarkers with or without carotid intima-media thickness improved the c-statistic to 0.822 and 0.820, respectively. All 3 models calibrated well but were similar in estimating the individual risk probabilities for advanced CAC (prevalence 9.97%, 10.63%, and 10.10% in the greatest quartiles of predicted probabilities vs 0.26%, 0.26%, and 0.26% in the lowest quartiles, respectively). In conclusion, in low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The biomarker combinations with and without carotid intima-media thickness were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.     

Consumption of high-oleic acid ground beef increases HDL-cholesterol concentration but both high- and low-oleic acid ground beef decrease HDL particle diameter in normocholesterolemic men

On the basis of previous results from this laboratory, this study tested the hypothesis that ground beef high in MUFA and low in SFA would increase the HDL-cholesterol (HDL-C) concentration and LDL particle diameter. In a crossover dietary intervention, 27 free-living normocholesterolemic men completed treatments in which five 114-g ground beef patties/wk were consumed for 5 wk with an intervening 4-wk washout period. Patties contained 24% total fat with a MUFA:SFA ratio of either 0.71 (low MUFA, from pasture-fed cattle) or 1.10 (high MUFA, from grain-fed cattle). High-MUFA ground beef provided 3.21 g more 18:1(n-9), 1.26 g less 18:0, 0.89 g less 16:0, and 0.36 g less 18:1(trans) fatty acids per patty than did the low-MUFA ground beef. Both ground beef interventions decreased plasma insulin and HDL(2) and HDL(3) particle diameters and increased plasma 18:0 and 20:4(n-6) (all P ≤ 0.05) relative to baseline values. Only the high-MUFA ground beef intervention increased the HDL-C concentration from baseline (P = 0.02). The plasma TG concentration was positively correlated with the plasma insulin concentration (r = 0.40; P < 0.001) and negatively correlated with HDL-C (r = -0.47; P < 0.001) and plasma 18:0 (r = -0.24; P < 0.01). Plasma insulin and HDL diameters were not correlated (r = 0.01; P > 0.50), indicating that reductions in these measures were not coordinately regulated. The data indicate that dietary beef interventions have effects on risk factors for cardiovascular disease that are independent (insulin, HDL diameters) and dependent (HDL-C) on beef fatty acid composition.     

New selective medium for the isolation of Neisseria gonorrhoeae.

GC-Lect, a new selective medium for the isolation of Neisseria gonorrhoeae which contains five antimicrobial agents, was evaluated with stock cultures and with 500 clinical specimens. With stock cultures, vancomycin-resistant Staphylococcus epidermidis that grew on modified Thayer-Martin medium (MTM) was inhibited on the new medium. Also, vancomycin-susceptible strains of N. gonorrhoeae were much less inhibited on the new medium than on Martin-Lewis agar or MTM. With oropharyngeal cultures of healthy volunteers, Capnocytophaga species were frequently isolated on MTM from two of three manufacturers but were completely inhibited on GC-Lect. In the clinical study, visible growth of N. gonorrhoeae occurred within 24 h in 72% of the positive cultures on GC-Lect, compared with only 52% on the reference medium. A total of 50 positive cultures were obtained with GC-Lect, compared with 49 obtained with MTM. The selectivity of GC-Lect was superior, with only 19 cultures producing growth of normal flora, compared with 78 cultures on MTM after 24 h of incubation. The selectivity was especially improved on GC-Lect with regard to yeasts (2 versus 30 cultures) and gram-positive cocci (5 versus 31 cultures).