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Biomedical subjects

T Roth

Publications and source records attributed to T Roth.

At least 109 records · Page 6Linked to original sources

Phase advance in moderately sleepy and alert normals.

Phase advanced sleep (by 4 hours) was studied in 28 healthy, normal men and women, aged 21-50 years, without nocturnal sleep or daytime sleepiness complaints. Eleven subjects (6 men and 5 women) with moderately short (< or = 10 minutes) average daily sleep latencies on the multiple sleep latency test (MSLT) were compared to 17 (11 men and 6 women) with relatively long (> or = 12 minutes) latencies. Nocturnal sleep on both a baseline and a shift night differed between the groups. The moderately "sleepy" group had shorter sleep latencies and less wakefulness during sleep than the moderately "alert" group. The phase advanced sleep schedule reduced sleep efficiency in both groups, but the moderately sleepy group showed a lessened effect of the shift. Additionally, sleep efficiency was reduced in the moderately sleepy group only during the first 2 hours of the sleep period, while sleep efficiency was uniformly disturbed in the moderately alert group throughout the night during the phase advance.

Adult↗

The frequency of multiple sleep onset REM periods among subjects with no excessive daytime sleepiness.

The multiple sleep latency test (MSLT) is a valuable tool in the assessment of excessive daytime sleepiness (EDS). Additionally, multiple sleep onset rapid eye movement periods (SOREMPs) are a frequent occurrence in patients with narcolepsy. To date, however, few studies have evaluated the frequency of SOREMPs in a population of healthy control subjects. Subjects participating in a variety of sleep studies were screened with a nocturnal clinical polysomnogram, followed by the MSLT. Subjects were required to be drug free and have no sleep-related symptoms or medical or psychiatric conditions. Of the 139 subjects who were screened, 24 (17%) had two or more SOREMPs. These individuals were more likely to be male, younger, and sleepier than those with one or zero SOREMPs. The etiology of two or more SOREMPs in healthy controls was not apparent from the clinical or polysomnographic evaluation. Although it is possible that these findings are early signs of narcolepsy, subjects reported being free of any sleep-related complaints. Further investigations into the determinants of multiple SOREMPs and their reliability among asymptomatic populations are warranted.

Adult↗

The effect of ketorolac on microvascular thrombosis in an experimental rabbit model.

This study was undertaken to evaluate the effect of ketorolac (Toradol), a potent cyclooxygenase inhibitor used for postoperative pain, on microvascular thrombosis in an established thrombosis model. Bilateral 3-mm arterial inversion grafts (n = 66) were constructed in the femoral arteries of New Zealand White rabbits. ALZET (ALZA Corporation, Palo Alto, Calif.) osmotic pumps were implanted in the external jugular veins for drug delivery. The blinded protocol called for the experimental animals to receive intravenous doses of ketorolac of 1.72 mg/kg per day (group 1) or 3.44 mg/kg per day (group 2), while control animals received equivalent volumes of saline. Patency was assessed at 7 days. Whereas 52 percent (13 of 25) of control vessels remained patent, 70 percent (14 of 20) and 86 percent (18 of 21) of group 1 and group 2 vessels, respectively, were patent at 1 week. This decrease in microvascular thrombosis with delivery of ketorolac was statistically significant (p = 0.0094). Ketorolac, at experimental doses approximating 9 and 18 mg IV q6h in a 70-kg man, demonstrated a statistically significant reduction in microvascular thrombosis. This study supports its use in clinical microvascular surgery.

Animals↗

Intraventricular cryptococcal cysts.

The case of a 55-year-old immunocompetent woman with central nervous system cryptococcosis and multiple intraventricular cysts is presented. The cysts did not enhance on MR and had signal characteristics similar to cerebrospinal fluid on T1- and T2-weighted images; their intensity was lower than cerebrospinal fluid on proton density-weighted images.

Cerebral Ventricles↗

A two-week sleep extension in sleepy normals.

Thirty-four healthy, normal young men and women (21-35 years), with no sleep complaints and a normal screening polysomnogram, some with short (< or = 6-minute) and some with long (> or = 16-minute) average daily sleep latencies on a screening multiple sleep latency test, were studied on two baseline nights (8 hours) and in the "sleepy" group, for 14 consecutive nights of extended (10-hour) or habitual (7.8 +/- 0.7-hour) bedtimes. The screening differences between the groups in average daily sleep latency were consistently seen on the two further baseline nights and days. The extension of bedtime in sleepy subjects was followed by an increase in average daily sleep latency relative to randomly chosen sleepy subjects maintained on their habitual sleep schedule for the 14 nights. The increase in average daily sleep latency was associated with a gradual reduction in sleep efficiency over the 14 nights. Some (36%) of the sleepy subjects did not have increased average sleep latencies during the 10-hour bedtime extension. Those showing no increase in average daily sleep latency had an immediate drop in sleep efficiency when the bedtime was increased to 10 hours, suggesting they were unable to sleep longer during the extension. Their short average daily sleep latency was a result of causes other than chronic insufficient sleep.

Adult↗

Activity and expression of the Na+/H+ exchanger in human endothelial cells cultured in high glucose.

Establishing whether high ambient glucose affects the plasma membrane Na+/H+ exchanger is relevant to understanding the adverse effects of high glucose on cell replication and the mechanisms of the increased exchanger activity encountered in diabetic patients with nephropathy. In 8 primary and 15 first-passage isolates of human endothelial cells cultured in 30 mmol/l glucose for 8.7 +/- 2.3 and 15.8 +/- 2.3 days, respectively, we determined Na+/H+ exchanger activity and mRNA levels. Activity was determined by measuring 22Na+ influx in the presence or absence of dimethylamiloride (DMA) after intracellular acidification. We also measured fibronectin mRNA because fibronectin provides signals for cell replication through the Na+/H+ antiporter. Control cells grown in 5 mmol/l glucose showed at morphologic confluency a total Na+ influx (in nmol.mg protein-1.min-1) of 10.1 +/- 3.2 in primary and 11.7 +/- 2.2 in first subculture, which was reduced to 5.3 +/- 0.3 in the presence of DMA. Paired cultures exposed to 30 mmol/l glucose and exhibiting pHi and cell densities identical to controls showed in both primary and first subculture a reduction in total Na+ influx (delta = -0.98 +/- 0.93 nmol.mg protein-1.min-1 p < 0.005) whereas DMA-resistant Na+ influx was identical to that of control. Neither chronic hypertonicity nor acute exposure to high glucose mimicked the effects of chronic high glucose. The level of the Na+/H+ exchanger isoform 1 (NHE-1) mRNA was unchanged by high glucose whereas fibronectin mRNA levels were increased 1.5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

Spermatology for understanding, managing and conserving rare species.

Most conventional spermatology research involves common mammalian species including livestock, laboratory animals and humans. Yet, there are more than 4500 mammalian species inhabiting the planet for which little is known about basic reproductive biology, including sperm characteristics and function. This information is important, not just as adjunct knowledge, but because the majority of these species are threatened with extinction, largely due to human-induced pressures. The field of conservation is changing rapidly, and global cooperation is emerging among a variety of wildlife enthusiasts, ranging from management authorities of nature reserves to curators of rare zoological collections. Conservation progress depends on systematic, multidisciplinary research first to answer basic questions, with new data then applied to endangered species management plans. The reproductive physiologist is a crucial component of this scheme. Reproduction is the essence of species survival, and enormous effort needs to be directed at these 'untraditional' research species, subspecies and populations. Spermatology research combined with simultaneous efforts in endocrinology, embryology and cryopreservation (among others) can lead to the successful application of assisted reproduction. Examples from this laboratory include an array of wild felid species and a rare cervid and mustelid. Obstacles to success are formidable, including unique species-specificities, diminished genetic diversity and a general lack of resources. Nonetheless, the field offers tremendous opportunities for generating unique knowledge of comparative interest and with conservation utility.

Animals↗

Zolpidem in the treatment of transient insomnia: a double-blind, randomized comparison with placebo.

Transient insomnia may be induced by stress, sleep in unfamiliar surroundings, jet lag and other factors. Zolpidem, a novel imidazopyridine hypnotic, has been shown to have hypnotic properties in most patients without significantly affecting next-day performance. Using the first-night effect in a sleep laboratory as a model of transient insomnia, this placebo-controlled, double-blind, parallel-group study evaluated the efficacy and safety of zolpidem in 462 normal volunteers. Zolpidem was tested at doses of 5, 7.5, 10, 15 and 20 mg, and statistical analysis of 7.5 mg and 10 mg was compared with placebo (unbalanced randomization). Compared with placebo, the 7.5 mg and 10 mg doses of zolpidem decreased sleep latency and increased sleep duration and maintenance (i.e. reduced number of awakenings). Zolpidem (7.5 mg or 10 mg) had no significant effect on next-day psychomotor performance. No statistically significant differences in the overall side-effect profiles were found between 7.5-mg and 10-mg zolpidem dose groups and placebo. This study demonstrates that zolpidem at 7.5 mg and 10 mg is effective in the treatment of transient insomnia.

Adult↗

Neuropsychological function in obstructive sleep apnea syndrome (OSAS) compared to chronic obstructive pulmonary disease (COPD).

Forty-nine men, 25 with obstructive sleep apnea syndrome (OSAS) and 24 with chronic obstructive pulmonary disease (COPD), were evaluated with a standard 8-hour nocturnal polysomnogram, multiple sleep latency test the following day and a neuropsychological test battery. The OSAS patients had more respiratory disturbances per hour of sleep, more stage 1 sleep and greater daytime sleepiness than COPD patients. The OSAS patients were as impaired as the COPD patients in neuropsychological test functioning, with the pattern of impairment nonspecific as to hypoxemic-sensitive versus sleepiness-sensitive tasks, with two exceptions. The OSAS patients performed more poorly on a test requiring sustained attention and considered sensitive to sleepiness, whereas the COPD patients performed more poorly on a test requiring motor skills and sensitive to hypoxemia. These deficits in psychomotor and attention appear to be specifically related to patients group (OSAS vs. COPD), but the other deficits found in complex reasoning and memory are nonspecific.

Attention↗

Hypersomnolence and neurocognitive performance in sleep apnea.

Two symptom clusters are prominent obstructive sleep apnea syndrome: excessive daytime sleepiness and neurocognitive difficulties. This article reviews studies that have attempted to determine the etiology and interrelation of these two symptom clusters. The research has clearly determined that the cause of the daytime sleepiness of obstructive sleep apnea syndrome is the fragmentation of sleep by the brief arousals that terminate each apneic event rather than the nocturnal hypoxemia that also occurs in obstructive sleep apnea syndrome. However, the daytime sleepiness and nocturnal hypoxemia appear to both contribute to the neurocognitive impairments of obstructive sleep apnea syndrome, and each seems to affect specific aspects of neurocognitive performance. The extent to which treatment reverses the neurocognitive impairments of obstructive sleep apnea syndrome is yet to be fully determined. The initial study suggests that the impairments are not completely reversed with treatment.

Humans↗

Prevalence of nocturnal oxygen desaturation in patients admitted to a geriatric rehabilitation unit.

Continuous oxygen measurement by digital oximetry is a well-established and widely used method. As reports in patients with cardiac disease have shown high prevalences of nocturnal oxygen desaturation, this study aimed to screen the patients admitted to a geriatric rehabilitation unit. Oxygen saturation was continously recorded during sleeptime in 103 unselected patients (52 women, 51 men) with a mean age of 77 y (65-90 y). The records were analysed according to standard rules concerning the frequency, duration and severity of periodic or phasic oxygen desaturations (ODES). Significant desaturations were found in 50/103 (48%) patients (43% women, 57% men) with a mean desaturation index (DESI) of 9.2 h-1. Periodic desaturations greater than 10 h-1 were found in 33% (35/103) patients with a mean DESI of 26/h in women and 20/h in men. Severe periods of desaturation (<80%) were found in 33% of women and in 41% of men. Patients with cardiac diseases showed the highest prevalence of total ODES (61%) and of periodic ODES (44%). Patients with lung diseases showed the highest prevalence of phasic ODES (43%). Patients admitted to the geriatric rehabilitation unit showed a considerably high prevalence of nocturnal oxygen desaturations. In contrast to earlier reports no significant influence of gender was found. The results presented here clearly support the urgent need for systematic sleep studies especially in elderly handicapped patients. Further investigations are needed to study clinical implications and the effects of therapeutic interventions.

Journal Article↗

Effects of theophylline on nocturnal sleep and daytime sleepiness/alertness.

To study the short-term effects of theophylline on sleep and wakefulness, 24 healthy men and women, aged 21 to 35 years, received each of three doses, 0, 3, and 6 mg/kg, of theophylline double-blind in a Latin Square design, administered to 12 subjects at 9 AM and to the other 12 at 11 PM. After the daytime administration, sleep latency was tested at 10 AM, 12 Noon, 2 PM, and 4 PM and divided attention and auditory vigilance performance were tested at 10:30 AM and 2:30 PM. After the nighttime administration, a standard 8-h polysomnogram was collected. On a separate day all subjects received a single 6-mg/kg dose at 9 AM and blood samples were drawn at 8:30 and 10:30 AM, 12:30 PM, 2:30 PM, and 4:30 PM. The serum theophylline levels for the 6-mg/kg dose peaked at 11.0 micrograms/mL and declined to 8.1 micrograms/mL by 4:30 PM. In the daytime administration, daytime mean sleep latency was increased by both doses and performance was improved by the high dose but not the low dose. In the nighttime administration, nocturnal sleep onset was delayed and total wake time was increased by the high dose but not the low dose. The low dose increased the amount of light stage 1 sleep without producing wakefulness.

Adult↗

Sleep disorders in patients on continuous ambulatory peritoneal dialysis.

Sleep complaints, habits, and medical history were surveyed in 81 patients chronically receiving continuous ambulatory peritoneal dialysis. Seventy-three percent of the sample reported insomnia, and 52% reported unintentional napping during the day. Behavioral factors (such as caffeine or alcohol use) or the severity of concurrent medical disease did not account for the sleep problems. Eighteen of these patients subsequently underwent polysomnography and objective measurement of daytime sleepiness. Clinically significant sleep apnea syndrome was present in 11. The presence of sleep apnea was associated with increased levels of psychological distress and daytime sleepiness. Periodic leg movements during sleep were also frequently observed but had minimal effect on sleep quality. Implications of these findings for clinical practice are discussed.

Adult↗

The effects of high glucose on human endothelial cell growth and gene expression are not mediated by transforming growth factor-beta.

BACKGROUND: Because accumulation of extracellular matrix is a prominent characteristic of the microangiopathy that complicates long-term diabetes, a pathogenetic role for transforming growth factor beta (TGF-beta) is being considered. Having observed that glucose levels mimicking diabetic hyperglycemia induce in vitro endothelial cell overexpression of extracellular matrix molecules, decreased replication, and increased levels of TGF-beta mRNA, we have examined whether the effects of high glucose are mediated by autocrine TGF-beta. EXPERIMENTAL DESIGN: TGF-beta levels were measured by bioassay in the media conditioned by human umbilical vein endothelial cells cultured in the presence of high (30 mM) or normal (5 mM) glucose concentrations. The effect of high glucose was tested on the proliferation of two epithelial cell lines, one (Mv1Lu) exquisitely sensitive to TGF-beta and the other (DR mutants) insensitive to the cytokine. To examine whether high glucose and TGF-beta affect cellular programs in a similar manner, the effects of high glucose and exogenous TGF-beta were compared on proliferation and gene expression of endothelial cells. RESULTS: Media conditioned by endothelial cells cultured in high or normal glucose contained similar amounts of TGF-beta (4.9 +/- 3.5 and 3.7 +/- 2.5 ng/10(6) cells, respectively (mean +/- SD)), all in the latent form. The replication of parental Mv1Lu cells and their DR mutants was decreased by high glucose to the same extent. Whereas the inhibitory effect of high glucose on endothelial cell replication was reversible, that of TGF-beta was not. Both perturbations induced up-regulation of fibronectin expression, but the effects were additive. Only TGF-beta induced overexpression of Type IV collagenase. CONCLUSIONS: These combined observations indicate that (a) endothelial cells exposed to high glucose do not secrete TGF-beta in excess of control cells, (b) there are growth-inhibitory effects of high glucose that are independent of TGF-beta, and (c) high glucose and TGF-beta exert their effects through distinct pathways and at different loci.

Cell Division↗

[Reconstruction methods for 3D imaging and quantification of intracoronary ultrasound cross-sectional images using biplanar fluoroscopy. Initial experiences in vitro and in vivo].

In this investigation, we studied the feasibility of 3D-reconstruction from 2D cross-sectional intracoronary ultrasound images. A computer-aided, automated 3D-reconstruction was used to generate cylindrical and sagittal format of vessels in vitro (n = 9) and in vivo (n = 48). Ultrasound 2D-images were acquired with a 20 MHz mechanical intracoronary ultrasound catheter (Boston Scientific). A slow pullback (about 1 mm/s) of the catheter was performed during continuous recording of the ultrasound images. The recorded 2D-images were then fed to an image processing computer. Correction and scaling of the axial vessel dimensions was performed by the assessment of the catheter position in the simultaneously recorded biplane fluoroscopy. Digitized data were then processed to 3D-images with use of voxel space modeling. The 3D-views from any plane can be reconstructed. The in-vitro study demonstrated that the reconstructed images were able to correctly portray the pathological changes of the vessel wall in all specimen as proved by pathologic examination. In the in-vivo study, 3D-reconstruction provided not only a spatial visualization of the coronary arterial disorders (such as coronary aneurysm, coronary dissection, spontaneous plaque rupture etc.) but also provides the potential to quantify the mass of lesions. By combining sagittal and cylindrical views, 3D-reconstruction enables longitudinal and orthogonal imaging of the both the vessel lumen and vessel wall, therefore, it has the advantage of cross-sectional viewing as obtained from intracoronary ultrasound and the longitudinal viewing as derived from coronary angiography. These preliminary results of the study indicate that 3D-reconstruction of coronary segments is a promising technique for studying coronary artery disease. Analysis can be based not only on single or multiple cross-sectional images but also on vessel segments facilitating serial studies as for instance studies assessing the progression and regression of atherosclerosis.

Aortic Dissection↗

Synthesis of novel androgen-linked phosphoramide mustard prodrugs and growth-inhibitory activity in human breast cancer cells.

Two steroid-linked phosphoramide mustard prodrugs, 7a and 7b, synthesized. The androgens testosterone and 19-nortestosterone were linked through the 17beta-position via an acetal bond to aldophosphamide (3). Proton-catalyzed, as well as cytochrome P450-mediated cleavage of the acetal bond resulted in the release of 3 which decays into the ultimate cytotoxic species, phosphoramide mustard. In a competitive cellular binding assay, the new prodrugs displayed approximately 10-12% affinity to androgen binding proteins in breast cancer cells, relative to testosterone (100%). In the sex hormone receptor-negative cell line MDA-MB231, the testosterone conjugate 7a and the 19-nortestosterone conjugate 7b have been found to be as effective as 4-hydroperoxycyclophosphamide (5). Both compounds were more active than 5 in receptor-positive cell lines. No significant differences in response were observed, however, between receptor-negative and receptor-positive cell lines.

Androgen-Binding Protein↗