Increased urinary free cortisol: a potential intermediate phenotype of essential hypertension

We evaluated urinary cortisol excretion as a potential intermediate phenotype of essential hypertension in 153 white patients with essential hypertension and 18 normotensive white control subjects. Analyses were controlled for dietary sodium and gender to adjust for potential confounding effects of these variables on cortisol excretion. Urinary cortisol excretion measured on both high- and low-salt diets was significantly related to hypertension by repeated measures ANCOVA (P=.02). Additional determinants of urinary free cortisol included dietary sodium intake and gender; cortisol excretion was significantly higher in men (P=.0006) and during a high-sodium diet (P=.0001). Maximum likelihood analysis showed urinary cortisol to have a bimodal distribution on both 200-mmol (P<.01) and 10-mmol (P<.002) sodium diets in hypertensive subjects. On the low-salt diet, the mean urinary cortisol in normotensive subjects (108.7+/-44.7 nmol/d) was similar to the mean of hypertensive subjects in the low mode (127.2+/-43.0 nmol/d). The high mode comprised 31.2% of the hypertensive population and had a mean urinary cortisol of 224.3+/-93.8 nmol/d. Subjects with the highest urinary free cortisol showed the least sensitivity of blood pressure to dietary sodium loading (P<.05). These data suggest that there is an association between salt-resistant hypertension and high urine cortisol levels. This association may have a genetic basis.     

Application of near-IR time-resolved spectroscopy and frequency response analysis for deep vein thrombosis detection

Frequency response analysis is applied to analyze NIR-TRS spectra in a tissue model with a simulated thrombus. The value changes in parameters obtained from frequency response analysis are correlated with heterogeneity position in three dimensions. The goal of this research is to noninvasively localize deep vein thrombosis in the human leg through the use of this novel combination.     

Nitric oxide measured with single-breath and tidal-breathing methods in asthma and COPD

Nitric oxide (NO) can be measured in exhaled air with the single-breath (SB) and tidal-breathing (TB) methods. To allow comparison between different laboratories, a European Respiratory Society task force recently reported guidelines for standardization of both methods. To facilitate comparison between laboratories further, this study investigated whether there is a difference between NO values measured with SB and TB methods in subjects with asthma or chronic obstructive pulmonary disease (COPD), and in healthy subjects. Moreover, the differences between groups were studied and the influence of smoking in asthma was assessed. Sixteen atopic nonsmoking asthmatics, 16 atopic currently smoking asthmatics, 16 nonatopic nonsmoking healthy controls, 16 nonatopic exsmokers with COPD and 16 nonatopic exsmoking healthy controls were studied. NO concentrations differed substantially between both methods. Mean NO concentrations were higher with the SB than with the TB method in nonsmoking and in smoking asthmatics and especially so with the higher NO values. Furthermore, NO values with both methods were higher in nonsmoking asthmatics than in nonsmoking healthy subjects. NO was not significantly different between exsmokers with COPD and healthy exsmokers. In conclusion nitric oxide values of the single-breath and tidal-breathing methods are not interchangeable. Both methods can be used to measure differences between groups.     

Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptors

PURPOSE: In this study, the authors present the biochemical, morphologic, and physiological analyses of a transgenic mouse model for retinal degeneration slow (RDS)-mediated retinitis pigmentosa caused by a proline 216 to leucine (P216L) amino acid substitution in rds/peripherin. METHODS: The authors assembled a mutant rds transgene that encodes rds/peripherin with a P216L substitution. Transgenic mice were generated on wild-type (+/+), heterozygous (rds-/+), and homozygous (rds-/rds-) null genetic backgrounds. These mice were analyzed biochemically, by light and electron microscopy, and by electroretinography. RESULTS: In P216L-transgenic mice on a +/- background, the authors observed expression-level-dependent photoreceptor degeneration and outer-segment shortening. Expression of the P216L transgene on an rds-/+ background resulted in more severe photoreceptor degeneration and outer-segment dysplasia than seen in nontransgenic rds-/+ mutants. Severely dysplastic outer segments were detectable in P216L transgenics on an rds-/rds-null background. The reduction in b-wave amplitudes by electroretinography were well correlated with the degree of photoreceptor degeneration, but not outer-segment dysplasia in these different rds mutants. CONCLUSIONS: The phenotype in P216L-transgenic mice on an rds-/+ genetic background probably is caused by a combination of two genetic mechanisms: a direct dominant effect of the P216L substituted protein, and a reduction in the level of normal rds/peripherin. The expression pattern of the normal and mutant genes in these animals is similar to that predicted for humans with RDS-mediated autosomal-dominant retinitis pigmentosa. These mice may thus be considered an animal model for this disease.     

Wear of visible light-cured restorative materials and removable partial denture direct retainers

Parenteral nutrition is a part of the nutritional support regimen of patients with AIDS-associated wasting syndrome and gastrointestinal dysfunction. The cholesterol (CHOL) level in human immunodeficiency virus (HIV) membrane is very high, and recent lipid formulations with high phospholipid (PL) content have demonstrated the ability to trap CHOL from endogenous sources, modifying the composition of cell membranes. We administered lipid-based home parenteral nutrition for 3 mo to malnourished AIDS patients. The patients were randomly divided into two groups: 23 received the regular 20% fat emulsion formulation, and 27 received a 2% formulation enriched 10-fold with PLs but containing the same amount of triglycerides. All patients gained weight and improved their activity level. Those receiving the high-PL composition showed increased serum CHOL concentrations (from 147 to 241 mg/dL; P < 0.01), but no increase was seen in the number of CD4 cells or improvement in immune function. HIV infectivity was not modified. Patients receiving regular PLs had significantly decreased (P < 0.02) IgA concentrations (from 776 to 300 mg/dL) and improved mitogen response to phytohemagglutinin and to concanavalin A. This formula, too, had no effect on HIV infectivity. We conclude that standard parenteral nutritional influences the nutritional and immune status of malnourished AIDS patients. A PL-enriched parenteral formulation can trap CHOL, but it does not affect the immune profile or HIV infectivity in patients with advanced disease.     

A prospective randomized repeat-crossover comparison of antitachycardia pacing with low-energy cardioversion

BACKGROUND: Multiprogrammable antiarrhythmia devices can treat monomorphic ventricular tachycardia (VT) with autodecremental overdrive pacing and/or with low-energy cardioversion. These two methods provide the opportunity to decrease patient discomfort typically experienced with high-energy pulses. Although both therapies are known to be effective, controversy persists over their relative safety and efficacy. METHODS AND RESULTS: The purpose of this study was to examine the safety and efficacy of autodecremental overdrive pacing and low-energy cardioversion in reproducibly terminating monomorphic VT in 24 patients with multiprogrammable antiarrhythmia devices. The protocol required that identical ECG morphology VT be reproducibly induced four times to assess the outcome of antitachycardia pacing and cardioversion twice for each patient in a randomized fashion. Each episode of VT was induced via the implanted device. Autodecremental overdrive pacing initially began with seven stimuli at 97% of the VT cycle length, decrementing by 10 msec per stimulus to a minimum coupling interval of 200 msec. If ineffective, autodecremental overdrive pacing was allowed to iterate three more times for a total of four pacing interventions. With each iteration, one stimulus was added to the pacing train. Similarly, with low-energy cardioversion, up to four therapeutic attempts were made, beginning with a 0.2-J pulse. If ineffective, pulse energy was increased to 0.4, 1.0, and finally 2.0 J. All interventions were automatic without human interference. VT (cycle length, 306 +/- 42 msec) was repeatedly terminated in 15 of 24 patients (63%) by autodecremental overdrive pacing and in 18 of 24 patients (75%) by low-energy cardioversion (p = 0.53). Eight of the 24 patients (33%) had their VT terminated repeatedly by both therapies. VT accelerated to faster VT or ventricular fibrillation by autodecremental overdrive pacing in four of 24 patients (17%) and by low-energy cardioversion in five of 24 (21%) (p = 0.88). Only one of the 24 patients (4%) accelerated with both therapies. No patient was unaffected by either therapy. CONCLUSIONS: In the manner programmed, autodecremental overdrive pacing and low-energy cardioversion have similar efficacy and acceleration rates. Response to one therapy does not predict response to the other.     

A clinicopathological study of infections in burn patients and importance of biopsy

Malignant peritoneal mesothelioma is a rare disease. The most frequent initial symptoms are abdominal pain, anorexia, marked weight loss and ascites. Clinical presentation as fever of unknown origin is exceptional. We report three cases diagnosed over a period of twenty years, two cases as fever of unknown origin and the third as prolonged fever. Three patients died within two months after diagnosis and prolonged fever was the clinical manifestation at the onset of the disease. It is important to take malignant peritoneal mesothelioma in the differential diagnosis of fever unknown origin.     

The prognostic significance of steroid receptor activity in tumor tissues of patients with primary breast cancer

The prognostic significance of steroid-receptor activity is still debatable. Discrepancies in results are probably attributable to few patients, heterogeneous patient populations, and short follow-up. We investigated the prognostic significance of estrogen- and progesterone-receptor (ER and PgR, respectively) activity as a continuous variable in a homogeneous patient population. The prognostic significance of steroid-receptor activity was examined in 329 node-negative and 320 node-positive unselected breast cancer patients. In node-negative patients, ER values of primary tumors between 100 and 400 fmol/mg protein appeared to be a significant predictor for low risk of recurrence, whereas high ER (> 400) revealed an unfavorable prognosis. The classic cutoff level of ER (< 10 fmol/mg proteins) had no prognostic significance, however. In patients receiving adjuvant chemotherapy--the node-positive breast cancer patients--the classic cutoff value of ER (10 fmol/mg protein) predicts significantly distant metastases-free survival and overall survival only in the first 4 years of follow-up after diagnosis. Progesterone receptor is a time-dependent prognosticator in node-negative breast cancer patients (cutoff point for PgR, 80 fmol/mg). In node-positive breast cancer patients treated with chemotherapy or a combination of chemo- and hormonal therapy, PgR values lower than 60 fmol/mg had a worse prognosis. The results show the poor performance of standard cutoff points for ER and PgR positivity in predicting prognosis. Better prognosis is related to higher receptor levels but this relation is predominantly time-dependent. Moreover, patients who have high ER levels have a prognosis that is worse when compared with intermediate ER levels. Standard cutoff points for steroid receptors should not be used to select patients for prognosis.