Treatment of Raynaud's phenomenon with triiodothyronine corrects co-existent autonomic dysfunction: preliminary findings.

Cardiovascular autonomic function was assessed in 9 subjects with Raynaud''s phenomenon. The underlying diseases were systemic lupus erythematosus (n = 5), systemic sclerosis (n = 3) and rheumatoid arthritis (n = 1). Five standard non-invasive tests, 3 of heart rate and 2 of blood pressure, were employed. Compared with age and sex matched controls (n = 25), the number of values abnormal was 24 of 45 (53%) overall and between one and 4 (median, 2) individually. Significant differences were present for 3 tests, two of heart rate and one of blood pressure. The subjects were given triiodothyronine, 60 to 80 micrograms per day, for vasospastic attacks. Autonomic function was reassessed between weeks 4 and 9 (9 subjects) and between weeks 12 and 18 (8 subjects) after introduction of triiodothyronine. Test results showed a considerable improvement. At the second reassessment, the number of values abnormal was now 5 of 40 (12.5%) overall and nil (n = 4) or one (n = 4) individually. Significant differences remained for one heart rate test only. Adverse side effects to triiodothyronine occurred in a single subject and were readily controlled. Evidence of somatic neuropathy was present electrophysiologically in all 9 subjects and clinically in 8. Triiodothyronine may have corrected autonomic dysfunction by increasing blood flow to ischaemic peripheral nerves or by acting on the autonomic system more directly. Further study of triiodothyronine in autonomic insufficiency appears merited.     

Effect of nutritional constraints on the biosynthesis of the components of the phosphoenolpyruvate: sugar phosphotransferase system in a fresh isolate of Streptococcus mutans.

A procedure for the purification of enzyme I (EI) and the protein HPr, the general components of the phosphoenolpyruvate:sugar phosphotransferase system, from Streptococcus mutans serotype c is presented. The method was also applied successfully to the purification of EI and HPr from Streptococcus salivarius, Streptococcus sobrinus, and Streptococcus sanguis. Using specific antibodies obtained against the proteins purified from S. mutans DR0001, we determined quantitatively by rocket electrophoresis the cellular levels of EI and HPr in a freshly isolated strain of S. mutans grown under various conditions in continuous culture. The activity of a few specific EIIs was also determined by an in vitro phosphorylation test. Results indicated that maximum EII activities for glucose, mannose, and 2-deoxyglucose were obtained under conditions of glucose limitation, at pH 7.0 and low dilution rate (D = 0.057/h). Increasing the amount of glucose or the dilution rate (D = 0.40/h) or decreasing the pH from 7.0 to 5.5 resulted in a 1.4- to 24-fold decrease in these activities. The EII activity for fructose was not influenced by the growth conditions in the same way as the other EIIs. The fructose EII was highest at pH 5.5 and at high dilution rate under conditions of glucose or nitrogen limitation and was always repressed at pH 7.0 and at low dilution rates. The intracellular levels of EI were also dependent on the growth conditions. The highest concentration (0.65 nmol/mg of protein) was observed in cells grown under glucose limitation at pH 7.0 and high dilution rate, and the lowest concentration (0.12 nmol/mg of protein) was found in cells grown under glucose excess at pH 7.0 and high dilution rate. The other general component of the phosphoenolpyruvate:sugar phosphotransferase system, the protein HPr, was not influenced significantly by varying growth conditions.     

Clinical assessment of medication adherence among HIV-infected children: examination of the Treatment Interview Protocol (TIP)

This paper presents findings of a multi-site study designed to document: (1) caregivers' regimen knowledge; (2) barriers to adherence; and (3) the relationships between adherence, regimen knowledge and barriers. Fifty-one predominantly female, African American parents and caregivers of HIV-infected children completed the Treatment Interview Protocol (TIP), a brief, structured interview designed to assess regimen knowledge and barriers to adherence. TIP data were compared to information obtained from medical records and pharmacy refill histories. Forty-nine per cent of children were considered adherent, defined as > or = 90% refill rate, which was significantly associated with virologic response. Significant regimen knowledge deficits were observed among caregivers, and inaccurate identification of prescribed medications was significantly associated with adherence. Caregivers identified 21 barriers to adherence, and poor adherence was significantly related to the number of barriers reported. Results indicate that the TIP is a successful tool for identifying regimen knowledge, potential adherence barriers and adherence problems. Results suggest that the TIP could be integrated into clinical practice as a quick, effective tool to identify poor adherers and guide interventions and treatment decision making.     

Gender-specific brachial artery blood pressure-independent relationship between pulse wave velocity and left ventricular mass index in a group of African ancestry

AIM: As it is uncertain whether arterial stiffness is related to left ventricular mass and left ventricle mean wall thickness independent of blood pressure measured at the brachial artery, we aimed to ascertain this effect in never-treated participants with a high prevalence of risk factors for large artery dysfunction. METHODS: The conventional and ambulatory blood pressure-independent relations between indices of large artery function and either left ventricular mass or mean wall thickness were determined in 309 never-treated randomly recruited South Africans of African ancestry with prevalent risk factors for large artery changes [24% were hypertensive, 63% were overweight/obese, and 17% had diabetes mellitus or abnormal blood glucose control (glycosylated hemoglobin A1c > 6.1%)]. Large artery function was assessed from applanation tonometry performed at the carotid, radial and femoral arteries and central augmentation index and aortic pulse wave velocity (carotid femoral pulse wave velocity) derived from these measures. Left ventricular mass indexed for height (left ventricular mass index) and mean wall thickness were determined using echocardiography. RESULTS: Pulse wave velocity was associated with left ventricular mass index (r = 0.67, P < 0.0001) and mean wall thickness (r = 0.61, P < 0.0001) in women, but not in men (r = 0.04-0.08) (P < 0.0001 for the interaction between pulse wave velocity and gender). On multivariate analysis with appropriate adjustments including either conventional systolic blood pressure, pulse pressure or mean arterial pressure, pulse wave velocity was independently associated with left ventricular mass index (partial r = 0.25, P < 0.005 after adjustments for systolic blood pressure) and with mean wall thickness (partial r = 0.17, P < 0.05 after adjustments for systolic blood pressure) in women, but not in men. With the inclusion of 24-h ambulatory rather than conventional systolic blood pressure, pulse pressure or mean arterial pressure in the regression equation, pulse wave velocity was similarly independently associated with left ventricular mass index (partial r = 0.39, P < 0.001 after adjustments for 24-h systolic blood pressure) and mean wall thickness (partial r = 0.33, P < 0.003 after adjustments for 24-h systolic blood pressure) in women, but not in men. Central augmentation index was not independently associated with left ventricular mass index or mean wall thickness. In women, the contribution of pulse wave velocity to left ventricular mass index or mean wall thickness independent of systolic blood pressure (standardized beta-coefficient for left ventricular mass index=0.37 +/- 0.13, P < 0.005) was equivalent to the contribution of systolic blood pressure (standardized beta-coefficient for left ventricular mass index = 0.38 +/- 0.13, P < 0.005). Moreover, after adjusting for clinic or ambulatory systolic blood pressure and other confounders, in women every one standard deviation increase in pulse wave velocity (2.1 m/s) translated into a 4.3 or 6.2 g/m increase in left ventricular mass index, respectively. CONCLUSION: Arterial stiffness is associated with left ventricular mass index and left ventricle wall thickness independent of conventional or ambulatory blood pressure and additional confounders in a never-treated population sample of women, but not men, of African ancestry with prevalent risk factors for large artery dysfunction.     

Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults

BACKGROUND: Schistosoma haematobium infection causes severe urinary disease and considerable mortality. The factors that determine disease progression from mild to severe stages are not fully understood. METHODS: Here we describe a cross-sectional epidemiological study of kidney and bladder diseases in 2 Dogon populations with different exposure to S. haematobium infection. RESULTS: Early and high exposure resulted in more-severe disease, especially among young subjects, without clear evidence of a more-rapid development of immunity. Nevertheless, 50%-60% of subjects of all age classes in both villages showed no evidence of disease. Kidney and bladder disease peaked biphasically among young subjects and adults >25 years old. The first peak corresponded with infections of maximum intensity, whereas the second peak occurred among adults with infections of very low intensity. Kidney disease was correlated with circulating anodic antigen concentration in serum, whereas bladder disease was correlated with egg count and eosinophil cationic protein concentration in urine. Kidney and bladder disease did not correlate. Severe kidney disease was more frequent in certain families. CONCLUSIONS: The frequency of urinary disease is increased by infections acquired early during life, is regulated by strong clinical immunity in certain subjects, and may be dependent on hereditary factors. Kidney and bladder disease may involve different mechanisms of pathogenesis, which may differ between children and adults.     

Impact of body weight on long-term survival after lung transplantation

STUDY OBJECTIVES: The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation. DESIGN AND PATIENTS: Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998. SETTING: University of Florida Health Science Center. RESULTS: Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, > or = 30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis. CONCLUSIONS: Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs.     

Effects of OP2113 on Myocardial Infarct Size and No Reflow in a Rat Myocardial Ischemia/Reperfusion Model

Cardiovascular Drugs and Therapy - The present study was to determine whether OP2113 could limit myocardial infarction size and the no-reflow phenomenon in a rat myocardial ischemia/reperfusion...     

Disease severity impacts the relationship of apelin with arterial function in patients with rheumatoid arthritis

Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic pressure (CSP), central pulse pressure (CPP), peripheral pulse pressure (PPP), pulse pressure amplification (PPamp), and forward wave pressure (Pf)) among 170 RA patients without cardiovascular disease. In multivariable regression models, apelin concentrations were not independently associated with arterial function measures (p?≥?0.15) in all patients. Inflammation markers were not consistently associated with apelin levels but joint deformity counts, Disease Activity Score in 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) impacted apelin-pressure pulsatility relations (interaction p?≤?0.05). In stratified analysis, apelin was associated with CSP (partial r?=???0.33, p?=?0.01), CPP (partial r?=???0.26, p?=?0.04), PPamp (partial r?=?0.27, p?=?0.03), and Pf (partial r?=???0.33, p?=?0.01) in patients without but not with joint deformities; apelin was related to CSP (partial r?=???0.24, p?=?0.05) in those with a DAS28 joint <?2.8 (median value) (partial r?=???0.24, p?=?0.05) but not ≥?2.8, and to CSP (partial r?=???0.36, p?=?0.003) in those with an erythrocyte sedimentation rate <?13 mm/h (median value) but not ≥?13 mm/h. Apelin is associated with reduced pressure pulsatility in RA patients without but not with a high inflammatory burden. A loss of apelin protective effects on arterial function may contribute to the link between RA severity and cardiovascular risk.