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Changing face and different countenances of prostate cancer: racial and geographic differences in prostate-specific antigen (PSA), stage, and grade trends in the PSA era.

The purpose of this investigation was to examine changes in pretreatment prostate-specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African-American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African-Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African-Americans. For African-Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health-policy decisions in the screening and treatment of prostate cancer.

Black People↗

Effect of anticonvulsants on nocturnal sleep in epilepsy.

Our objective was to determine, in three separate studies, the effects of controlled-release carbamazepine (CBZ-CR), lamotrigine (LTG), and gabapentin (GBP) on nocturnal sleep in epilepsy. Antiepileptic drugs (AEDs) control seizures and also modify hypnic structure. Despite widespread clinical use, their effects on sleep are not well known. PSG was performed in all three studies as follows: CBZ-CR: at baseline, after initial administration of CBZ-CR 400 mg, and after 1 month of CBZ-CR treatment (400 mg BID) in a sample of seven temporal lobe epileptic (TLE) patients. Results were compared with those of nine healthy volunteers; LTG: at baseline, after 3 months of stable treatment with LTG (300 mg/day); GBP: at baseline, after 3 months of stable treatment with GBP (1800 mg/day). Significant findings are as follows for each study. The acute administration of CBZ-CR increased number of stage shifts, reduced REM sleep, and increased REM sleep fragmentation. In the TLE group, these effects were almost completely reversed after chronic treatment. LTG increased REM sleep, reduced number of entries into REM sleep, decreased number of phase shifts, and decreased percentage of slow-wave sleep. GBP increased REM sleep percentage, increased mean duration of REM periods, reduced number of awakenings, and reduced stage 1 sleep percentage. We conclude that CBZ-CR disrupts REM sleep, but only during acute administration. LTG and GBP improve sleep stability while reducing seizures.

Acetates↗

Reevaluation of the 1997 TNM classification for renal cell carcinoma: T1 and T2 cutoff point at 4.5 rather than 7 cm. better correlates with clinical outcome.

PURPOSE: We analyzed the effects of the change in TNM classification from the 1987 to the 1997 version and suggest a modified tumor size cutoff point between T stages 1 and 2 for renal cell carcinoma. MATERIALS AND METHODS: We evaluated a database containing the records of 661 patients who underwent nephrectomy between 1989 and 1999. The effect of the change in TNM classification on the distribution of patients between stages, the rates of M+ and N+ disease, and the local and distant recurrence rates were outlined for 280 patients with T stages 1 and 2 disease. The Cox model was used to identify the optimal cutoff point between T1 and T2 disease, and the resulting effect of adopting this cutoff was outlined. RESULTS: A total of 174 and 128 cases were down staged from 1987 version stage T2 to 1997 version stage T1 and from 1987 TNM stage II to 1997 TNM stage I, respectively. Survival was not significantly different in patients with 1997 TNM stages I and II disease due to a lack of survival difference during the first 2 years of followup. Stage shift also caused an increase in average tumor size, the proportion of patients with high grade cancer, and M+ and N+ disease at diagnosis in 1997 stages T1 and T2 as well as an increase in the proportion of 1997 stage T2N0M0 cases at diagnosis with systemic failure. Analysis of 11 potential cutoff points between 1 and 10 cm. revealed that 4.5 cm. was most predictive of patients survival (hazards ratio 4.99, p = 0.0001). Using this cutoff resulted in improved discriminatory power of the TNM classification and a moderating effect on the distribution of patients, average tumor size, high grade disease, M+ and N+ disease at diagnosis, and systemic failure between T(14.5) and T(24.5) compared with 1997 T1 and T2. CONCLUSIONS: Our data imply that the current cutoff point of 7 cm. between stages T1 and T2 tumors is too high. Lowering the cutoff to 4.5 cm. resulted in better discriminatory power of the TNM classification in our dataset. This observation should be further validated by external data.

Adult↗

Ethylbenzene removal in a multiple-stage biofilter.

In practice, biofilters are often conceived as entire, single-unit systems. However, the activity of a biofilter varies greatly over its depth. For a given period, each stage of the biofilter dominates ethylbenzene removal. Ethylbenzene was continuously removed in a mixed-medium biofilter. The overall removal efficiency of the ethylbenzene ranged from 70% to greater than 99%. In the upflow biofilter, the most dominant ethylbenzene degrading stage shifted consecutively from the bottom to the top of the reactor. Average water content throughout the biofilter media was relatively consistent. However, the water content of each stage fluctuated dramatically and was correlated with the ethylbenzene removal rate. Without any water addition, the biofilter was operated for 62 days above the target removal efficiency of 80%. A 9-month slow-release fertilizer, mixed with composting media, was an effective way to eliminate the nutrient deficiency in the biofilter operation.

Air Pollutants↗

Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man.

Attentional "set" shifting was assessed in a group of 20 neurosurgical patients with localized excisions of the frontal lobes, a group of 20 patients with unilateral temporal lobe lesions and a group of 11 patients who had undergone amygdalo-hippocampus removal. These three patient groups were compared with groups of both young (age-matched) and elderly normal control volunteers on a computerized test of visual discrimination learning involving both an intra- and an extra-dimensional shift. The frontal lobe group were selectively impaired in their ability to shift response set to a previously irrelevant dimension but not to shift attention to new exemplars of a previously relevant dimension. A similar pattern was observed in the elderly group of normal control volunteers. By comparison, both the temporal lobe patients and the amygdalo-hippocampectomy patients were unimpaired in their ability to perform either shift, although both groups had significantly prolonged selection latencies at the extra-dimensional shift stage of the task. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of a specific attentional set shifting deficit following frontal lobe damage.

Adult↗

Sleep alterations after acute administration of carbamazepine in cats.

Little is known about the effects of carbamazepine (CBZ) on sleep despite the relationship between sleep and epilepsy and the common clinical use of CBZ. As part of a larger study on sleep and interictal activity in kindled cats, we performed sleep recordings in 11 normal cats before and after acute administration of CBZ. Epidural screws (frontooccipital) and depth electrodes (amygdala and hippocampus) were implanted bilaterally for EEG recording. Supraorbital screws and neck intramuscular electrodes were inserted for EOG and EMG. Ten days after electrode implantation, recordings were made of animals for 2 consecutive nights to assess baseline sleep patterns. Before the third night, cats received a single oral dose of 100 mg CBZ. After washout, a second similar drug administration was given before the fourth night. Recordings were scored for wakefulness, stage I and II of NREM sleep, REM sleep, number of stage shifts, awakenings, and REM onsets. The administration of CBZ produced a significant decrease in duration and percentage of REM sleep (p less than 0.001) and an increase in stage I NREM (p less than 0.05). Total sleep time was increased (p less than 0.05); awakenings were shorter (p less than 0.01), and stage I episodes were longer (p less than 0.01).

Animals↗

NREM sleep instability is reduced in children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: To evaluate non-rapid eye movement sleep instability (NREM), as measured by the cyclic alternating pattern (CAP), in a cohort of children with attention-deficit/hyperactivity disorder (ADHD) and normal controls. DESIGN: Prospective study. SETTINGS: Sleep laboratory. PARTICIPANTS: Twenty consecutive outpatients with ADHD (18 boys and 2 girls; age range 6-13 years, mean age 9.3 years) and 20 normal children matched for age and socioeconomic status underwent polysomnographic recordings for 2 consecutive nights in a standard laboratory setting. Sleep was visually scored for sleep macrostructure and CAP, according to standard criteria. MEASUREMENTS AND RESULTS: Children with ADHD showed significantly reduced sleep duration and increased rate of stage shifts. All children with ADHD had an apnea-hypopnea index less than 1. Those with ADHD presented lower total CAP rates and lower CAP rates during sleep stage 2 than did normal controls. Moreover, in children with ADHD, we found a lower number of CAP sequences and a reduced total A1 index, mainly in light sleep (sleep stages 1 and 2). We did not find differences in A subtype percentages, but there was a longer duration of A1 subtypes in children with ADHD. CONCLUSIONS: Children with ADHD showed a lower CAP rate and a lower number of CAP sequences; this supports the hypothesis of the existence of a hypoarousal state in these patients.

Adolescent↗

Immunohistochemical studies on the development of the hypothalamo-hypophysial system in Xenopus laevis.

BACKGROUND: Few attempts have been made to clarify the relational development of the hypothalamo-adenohypophysial and -neurohypophysial systems in species higher than amphibians. METHODS: The appearance and topographical distribution of endocrine and neuroendocrine cells and fibers in these systems were immunohistochemically examined in the larvae of Xenopus laevis from immediately before hatching (stage 32, Nieuwkoop and Faber's classification) to the end of metamorphosis (stage 66). RESULTS: (1) Each endocrine cell differentiated until the middle premetamorphic period. MSH cells initially appeared in the posterior half of the pituitary anlage at stage 35/36, followed by the differentiation of GH cells at stage 39 in the middle part, PRL cells at stage 46 in the anterior half of the pituitary anlage, and LH cells at stage 50 in the posterior two thirds of the pars distalis. With the progression of development, the cells which differentiated at early stages shifted from their initial positions; MSH cells, to the pars intermedia; and GH cells, to the posterior half of the pars distalis. 2) Oxytocin and vasopressin fibers were observed at stage 47/48 in the median eminence, and converged to the pars nervosa at later stages. 3) Neuroendocrine fibers innervated the median eminence during the middle premetamorphic to prometamorphic period: SOM fibers, at stage 45; CRH, 47/48; GRH, 48; dopamine, 58; and LHRH, 60. The cells containing these hormones were observed in the (presumptive) preoptic and/or infundibular nuclei. CONCLUSION: These results suggest the following three chronological steps in the development of hypothalamo-hypophysial systems and their target organs: independent development of target organs at early developmental stages; appearance of hypophysial hormones to control the development of target organs at middle developmental stages; appearance of hypothalamic hormones to control the function or maturation of the hypophysis at late developmental stages.

Aging↗

Effect of lansoprazole on peptic ulcers.

Lansoprazole is the first proton pump inhibitor developed in Japan. We studied the clinical efficacy of lansoprazole 30 mg q.d. on peptic ulcers and the subsequent relapse rates. The endoscopic healing rate of gastric ulcers (n = 86) after 8 weeks of treatment and duodenal ulcers (n = 52) after 6 weeks of treatment were 94.2 and 96.2%, respectively. The endoscopic S2-stage shift rates in gastric and duodenal ulcers were 45.5 and 65.4%, respectively. Factors affecting healing rates of gastric ulcers included colonization by Helicobacter pylori, the size and depth of the ulcers, pretreatment stage, and ulcer history, whereas those factors did not influence healing in duodenal ulcers. The clearance rates of H. pylori after lansoprazole treatment were 54.5% in patients with gastric ulcer and 66.7% in those with duodenal ulcer. The cumulative relapse rates after 1 year with standard maintenance therapy of H2-receptor antagonists (ranitidine, famotidine, and cimetidine) were 15.8% for gastric ulcer and 21.2% for duodenal ulcer. In conclusion, lansoprazole is highly effective in peptic ulcer disease and there are few relapses after treatment. Furthermore, it is suggested that lansoprazole is efficacious against H. pylori at usual clinical doses.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effect of benzodiazepine hypnotics on all-night sleep EEG spectra.

The effect of a single, oral bedtime dose of the benzodiazepine hypnotics flunitrazepam (FR; 2 mg), flurazepam (FR; 30 mg), and triazolam (TR; 0.5 mg) on the sleep stages and the sleep EEG was investigated in eight healthy, young subjects. In comparison to the placebo night, all drugs reduced the percentage of stage 1 and REM sleep, increased stage 2, and decreased the number of stage shifts. For FN and FR, some of these changes persisted in the postdrug night. All-night spectral analysis of the EEG showed a reduction of low-frequency activity (0.25-10.0 Hz) in stages 2, 3 + 4 and REM sleep, changes that persisted for all three drugs in the post-drug night. In the drug nights, activity in the spindle frequency range (11-14 Hz) was enhanced particularly in stage 2 and 3 + 4, activity in the high frequency range (17-25 Hz) particularly in REM sleep and stage 1. In the first third of the drug night, the depression of low-frequency activity in stage 2 was either absent (FR) or less prominent (FN, TR) than in the following part of the night. The results demonstrate that benzodiazepine hypnotics induce specific changes in the EEG spectra which reflect the immediate and residual drug effects more sensitively than conventional sleep scores.

Adult↗

Sleep pattern alterations and brief airway obstructions in overweight infants.

The sleep characteristics of 10 overweight infants were monitored polysomnographically and compared with those of 10 age- and sex-matched control infants with no weight excess. The infants were selected from a well-babies clinic. Infants were assigned to the weight excess group if their weight was greater than 120% of ideal weight/height for age. There were six boys and four girls in both groups, with a median age of 23.5 weeks in the weight excess group and 22.0 weeks in the control group. The infants with weight excess spent significantly less time sleeping in non-rapid-eye-movement (NREM) sleep stage 3-4 and more time in indeterminate sleep than their matched controls. The infants with weight excess had also significantly more gross body movements and more sleep stage shifts than the control infants. Brief airway obstructions were found significantly more frequently in the weight excess group than in the control group. Seven overweight infants showed a total of 74 brief airway obstructions; 41 occurred in NREM sleep stage 1 or 2 and 14 in rapid-eye-movement (REM) sleep. The median duration of the obstructive episodes was 8 s (range 3-13 s). Of the 10 control subjects, only 2 had one obstructive episode each, lasting 3 and 4 s and occurring during REM sleep. Only one mixed apnea of 6.5 s was recorded in a 39-week-old overweight boy. The obstructive episodes were accompanied by a median fall in heart rate of 9% (range 0-51%) and by a median fall in oxygen saturation of 0.9% (range 0-10%).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗

Effect of the 1,5-benzodiazepines, clobazam and triflubazam, on sleep in man.

1 The effect of the 1,5-benzodiazepines, clobazam (10 and 20 mg) and triflubazam (20 and 40 mg), on sleep was studied in six healthy males using electroencephalography for sleep measures and analogue scales for subjective assessments of well being and sleep quality. The effect of clobazam was limited to the night of ingestion. There was some evidence from subjective assessments that the effect of triflubazam may have persisted beyond the night of ingestion. 2 No effect of clobazam or triflubazam was observed on total sleep time, stage shifts in the first 6 h or latency to the first rapid eye movement period of sleep. With clobazam sleep onset latency was shortened (P less than 0.05), but this effect was not seen with triflubazam. The latency to stage 3 was shortened by both drugs. There was evidence of reduced duration of awake (stage 0) activity and drowsy (stage 1) sleep with both drugs. 3 The percentage stage 1 sleep was reduced by clobazam (10 and 20 mg) and by triflubazam (20 mg) (P less than 0.05), though the effect was not significant with triflubazam (40 mg). Clobazam (20 mg) increased the percentage stage 2 sleep (P less than 0.05), but reduced the percentage stage 3 (P less than 0.01) and stages 3 + 4 (P less than 0.05) sleep. There were no other effects on percentage of total sleep time occupied by various sleep stages or in duration (min) of sleep stages, except that the duration (min) of sleep stages, except that the duration (min) of stage 2 sleep in the second 2 h interval of sleep was increased with clobazam (20 mg) (P less than 0.01). 4 Subjects reported impaired sleep with triflubazam (40 mg) (P less than 0.05), and a sense of less wakefulness the morning after ingestion of clobazam (10 and 20 mg) (P less than 0.01) and triflubazam (40 mg) (P less than 0.05).

Adult↗

Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems.

Although the interaction between sleep and pain is generating considerable interest (NIH Technology Assessment Panel, 1996), it is still unknown if chronic pain is the cause or effect of poor sleep. To further this understanding, subjects free of pain and sleep problems need to be studied in order to assess their response to pain during sleep, defined as a behavioral and a physiological state in which sensory processing is altered. (For example, while auditory perception remains active, other sensory inputs are facilitated, attenuated, or suppressed (Velluti, 199746 degrees C) was statistically greater in the lighter sleep stage 2 (48.3%) than in the deeper stages 3&4 (27.9%). A nocifensive behavioral-motor response was associated with only 2.5% of the 351 heat pain stimuli. Two other markers of sleep quality-sleep stage shift and awakening-were not influenced by the thermal stimuli. None of the subjects demonstrated any burns in the morning following the thermal stimulations applied during sleep. We conclude that the processing of nociceptive inputs is attenuated across sleep stages.

Adult↗

Longitudinal sleep patterns during pubertal growth: four-year follow up.

There were little or no indications of differences in sleep outcomes between the sexes. Results indicate a disturbance of sleep on initial laboratory nights relative to later nights. The results reported here clearly document the persistence of these effects from year to year. For the most part, sleep characteristics during the 4 years immediately after onset of puberty appear to represent a typical phase in the gradual patterns of changes across all ages. Total sleep time decreased markedly from 560 min in age range 10-12 to 424 min in age range 20-29, with our puberty subjects as intermediate levels. Puberty subjects has an average of 2.5 awakenings/night in the first 2 years as compared with 1.2/night in the last 2 years. The number of sleep stage shifts during the night varied around a constant mean value of approximately 37/night throughout all ages. The number of rapid eye movement (REM) period during the night decreased sharply for individuals from childhood (6.9/night) through adolescence (4.0/night), remaining constant thereafter. Percentages of the various sleep stages were fairly constant for individuals from age range 10-12 through age 30-39. Our puberty subjects had percentage profiles in near perfect agreement with the normal ontogenetic process. Normative data suggest that slow wave sleep reaches a peak at some point during the teen years.

Adaptation, Physiological↗

What is early lung cancer? A review of the literature.

The dismal cure rate of patients with lung cancer and the stage shift hypothesis have propelled the interest to perform screening at large, despite that previous randomized clinical trials failed to show any mortality benefit and the controversial issue of overdiagnosis. Due to early detection programs, a larger number of individuals at risk will be found to harbor small and potentially malignant early stage lesions. The application of non- and minimal invasive techniques for early detection, staging and treatment will become increasingly important. This review deals with the available clinical, surgical and pathological data focusing on early lung cancer lesions < or =1 cm. Literature data from both centrally located and parenchymal lesions < or =3 cm. have been analyzed. For all sub-centimeter lesions, minimal invasive staging and treatment approaches must still be considered inappropriate. Less invasive and less extensive treatment methods may be considered in high risk individuals with < or =1 cm. peripheral lesion showing > or =50 ground glass opacity on high resolution CT scan and those with superficial lesion in their central airways without deeper tumor invasion in the bronchial wall. Caution is necessary, however, as clinical staging remains inferior to pathological staging which is based on tissue samples collected after complete tumor removal and mediastinal lymph nodes dissection have been performed.

Humans↗

Effect of continuous positive airway pressure versus supplemental oxygen on sleep quality in obstructive sleep apnea: a placebo-CPAP-controlled study.

STUDY OBJECTIVE: We investigated the short-term effectiveness of continuous positive airway pressure (CPAP) and oxygen in improving sleep quality in patients with obstructive sleep apnea (OSA). DESIGN: Randomized, double-blind, placebo-controlled, parallel study. SETTING: General Clinical Research Center at a university hospital. PATIENTS: Seventy-six patients with untreated OSA. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatments (CPAP, placebo-CPAP, or nocturnal oxygen at 3 L per minute) for 2 weeks. Sleep quality was assessed at baseline and after 1 and 14 days of therapy. Repeated-measures analysis of variance was used to evaluate treatment and time effects, and their interaction. MEASUREMENTS AND RESULTS: Sixty-three patients completed the protocol. When compared with placebo-CPAP and nocturnal oxygen, CPAP increased rapid eye movement (REM) sleep and significantly reduced stage 1 sleep and the number of stage shifts (p < or = .003). CPAP improved, to within normal limits, the apnea-hypopnea index, total arousal index, and mean oxyhemoglobin saturation (p < or = .001). The effects of CPAP were apparent during the first night of therapy. Oxygen improved only mean nocturnal saturation (p = .009). CPAP had no significant effect on stage 2 sleep or slow-wave sleep. CONCLUSIONS: CPAP was associated with an improvement in sleep quality in patients with OSA by consolidating sleep, reducing stage 1 sleep, and improving REM sleep. CPAP was effective in correcting the respiratory and arousal abnormalities of OSA. The effectiveness of supplemental oxygen was limited to oxyhemoglobin desaturation.

Arousal↗

Relationship between enteric migrating motor complex and the sleep cycle.

To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.

Adult↗

EEG sleep studies in patients with generalized anxiety disorder.

Sleep polygraphic recordings were performed during 3 consecutive nights in 12 inpatients with generalized anxiety disorder (GAD) in comparison with age- and sex-matched groups of patients with major depressive disorder (MDD) and normal subjects. GAD patients differed significantly from those with MDD. A lower number of awakenings and stage shifts in night 1 and the mean of the 3 nights and a shorter rapid eye movement (REM) duration in night 1 but longer REM latency in the mean of the 3 nights were observed in GAD in comparison to MDD. GAD patients also showed a significantly longer sleep onset latency and shorter duration of total sleep time and Stage 2 than control subjects. Electroencephalographic sleep recordings, as well as other laboratory tests, may help the clinician to differentiate anxiety from depressive disorders.

Adult↗