Cardiopulmonary and metabolic physiology during hemodialysis and inter/intradialytic exercise.

Hemodialysis is associated with numerous symptoms and side effects that, in part, may be due to subclinical hypoxia. However, acute cardiopulmonary and metabolic physiology during hemodialysis is not well defined. Intradialytic and interdialytic exercise appear to be beneficial and may alleviate these side effects. To better understand these potential benefits, the acute physiological response to exercise should be evaluated. The aim of this study was to compare and characterize the acute physiological response during hemodialysis, intradialytic exercise, and interdialytic exercise. Cardiopulmonary physiology was evaluated during three conditions: 1) hemodialysis without exercise (HD), 2) intradialytic exercise (IDEx), and 3) interdialytic exercise (Ex). Exercise consisted of 30-min constant load cycle ergometry at 90% V̇O2AT (anaerobic threshold). Central hemodynamics (via noninvasive bioreactance) and ventilatory gas exchange were recorded during each experimental condition. Twenty participants (59 ± 12 yr, 16/20 male) completed the protocol. Cardiac output (Δ = -0.7 L/min), O2 uptake (Δ = -1.4 mL/kg/min), and arterial-venous O2 difference (Δ = -2.0 mL/O2/100 mL) decreased significantly during HD. Respiratory exchange ratio exceeded 1.0 throughout HD and IDEx. Minute ventilation was lower (P = 0.001) during IDEx (16.5 ± 1.1 L/min) compared with Ex (19.8 ± 1.0 L/min). Arterial-venous O2 difference was partially restored further to IDEx (4.6 ± 1.9 mL/O2/100 mL) compared with HD (3.5 ± 1.2 mL/O2/100 mL). Hemodialysis altered cardiopulmonary and metabolic physiology, suggestive of hypoxia. This dysregulated physiology contributed to a greater physiological demand during intradialytic exercise compared with interdialytic exercise. Despite this, intradialytic exercise partly normalized cardiopulmonary physiology during treatment, which may translate to a reduction in the symptoms and side effects of hemodialysis.NEW & NOTEWORTHY This study is the first, to our knowledge, to directly compare cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise, and interdialytic exercise. Hemodialysis was associated with increased respiratory exchange ratio, blunted minute ventilation, and impaired O2 uptake and extraction. We also identified a reduced ventilatory response during intradialytic exercise compared with interdialytic exercise. Impaired arterial-venous O2 difference during hemodialysis was partly restored by intradialytic exercise. Despite dysregulated cardiopulmonary and metabolic physiology during hemodialysis, intradialytic exercise was well tolerated.

Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study.

Maximal O2 uptake is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. While determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal constant load exercise. By comparing individuals with ESRD and healthy controls, the aim of this exploratory study was to characterize mechanisms of exercise intolerance in participants with ESRD by assessing cardiopulmonary physiology at rest and during exercise. Resting spirometry and echocardiography were performed in 20 dialysis-dependent participants with ESRD (age: 59 ± 12 yr, 14 men and 6 women) and 20 healthy age- and sex-matched controls. Exercise tolerance was assessed with ventilatory gas exchange and central hemodynamics during a maximal cardiopulmonary exercise test and 30 min of submaximal constant load exercise. Left ventricular mass (292 ± 102 vs. 185 ± 83 g, P = 0.01) and filling pressure (E/e': 6.48 ± 3.57 vs. 12.09 ± 6.50 m/s, P = 0.02) were higher in participants with ESRD; forced vital capacity (3.44 ± 1 vs. 4.29 ± 0.95 L/min, P = 0.03) and peak O2 uptake (13.3 ± 2.7 vs. 24.6 ± 7.3 mL·kg-1·min-1, P < 0.001) were lower. During constant load exercise, the relative increase in the arterial-venous O2 difference (13 ± 18% vs. 74 ± 18%) and heart rate (32 ± 18 vs. 75 ± 29%) were less in participants with ESRD despite exercise being performed at a higher percentage of maximum minute ventilation (48 ± 3% vs. 39 ± 3%) and heart rate (82 ± 2 vs. 64 ± 2%). Ventilatory and chronotropic incompetence contribute to exercise intolerance in individuals with ESRD. Both are potential targets for medical and lifestyle interventions.

High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study.

OBJECTIVE: To compare the efficacy of corticotropin (ACTH) (150 U/m2/day) and prednosone (2 mg/kg/day) given for 2 weeks, in suppressing clinical spasms and hypsarrhythmic electroencephalogram (EEG) in infantile spasms (IS). AACTH and prednisone are standard treatments for IS. ACTH at high doses causes severe dose- and duration-dependent side effects, but may be superior to prednisone, based on retrospective or uncontrolled studies. Blinded prospecive studies have shown equal efficacy of prednisone and low-dose ACTH, and low versus high-dose ACTH. DESIGN: A prospective, randomized, single-blinded study. SUBJECTS AND METHODS: Patient population consisted of consecutive infants fulfilling entry criteria, including the presence of clinical spasms, hypsarrhythmia (or variants) during a full sleep cycle video-EEG, and no prior steroid/ACTH treatment. Response required both cessation of spasms and elimination of hypsarrhythmia by the end of the 2-week treatment period, as determined by an investigator "blinded" to treatment. Treatment of responders was tapered off over 12 days; those failing one hormone were crossed-over to the other. RESULTS: OF 34 eligible infants, 29 were enrolled. Median age of patients was 6 months. Twenty-two infants were "symptomatic" with known or suspected cause, and seven were cryptogenic (two normal). Of 15 infants randomized to ACTH, 13 responded by EEG and clinical criteria (86.6%); Seizures stopped in an additional infant, but EEG remained hypsarrhythmic (considered a failure). Four of the 14 patients given prednisone responded (28.6%,, with complete clinical-EEG correlation), significantly less than with ACTH, (chi2 test). CONCLUSIONS: Using a prospective, randomized approach, a 2-week course of high-dose ACTH is superior to 2 weeks of prednsone for treatment of IS, as assessed by both clinical and EEG criteria.

Cerebrospinal fluid corticotropin and cortisol are reduced in infantile spasms.

Infantile spasms respond to ACTH, and levels of the hormone in cerebrospinal fluid of untreated infants with this disorder were found to be lower than in age-matched controls. In this study we analyzed cerebrospinal fluid cortisol and ACTH using improved immunoassays in a larger cohort of infants with infantile spasms. Analysis of 20 patients and 15 age-matched controls revealed significantly lower levels of both ACTH and cortisol in the cerebrospinal fluid. These data, combined with the efficacy of ACTH and glucocorticoids for infantile spasms, support an involvement of the brain-adrenal-axis in this disorder.

Clinical utility of video-EEG monitoring.

This study investigated the efficiency of simultaneous video-electroencephalography (EEG) monitoring in documenting paroxysmal events, the value in clinical diagnosis, and the effect on treatment. In this retrospective review, 230 children underwent this procedure between January, 1990 and December, 1992. The data demonstrated that video-EEG monitoring can be used as a daytime procedure with a high success rate (80%) in detecting and differentiating the nature of recurrent paroxysmal behaviors that have occurred on a daily basis. Video-EEG monitoring has a high diagnostic rate in differentiating seizure versus nonseizure events (70%), in classifying seizure types (88%), and in evaluating the candidacy for epilepsy surgery (64%). Video-EEG diagnosis resulted in an alteration of clinical management in 45% of patients. Continuous video-EEG monitoring is an efficient and valuable procedure in the diagnosis and management of paroxysmal disorders in children.

Abnormal somatosensory evoked potentials in patients with classic galactosemia: correlation with neurologic outcome.

In classic galactosemia, long-term neurologic sequelae can include low cognitive functioning and a curious neurologic syndrome with tremors, dysmetria, and ataxia. An abnormal white-matter signal on cerebral magnetic resonance imaging (MRI) is present in almost all patients; some have mild cerebral or cerebellar atrophy and focal white-matter lesions. The present study was undertaken to assess the integrity of myelinated pathways by recording somatosensory evoked potentials. Results were correlated with age at diagnosis, severity of illness, age at evoked potentials, neurologic examination, MRI studies and cognitive outcome as measured by the Woodcock-Johnson Revised Standard Cognitive Battery. Evoked potentials were abnormal in 17 (28%) of 60 patients who had median nerve, and 26 (77%) of 34 patients who had posterior tibial nerve studies. Abnormalities of the central rather than the peripheral nervous system were most common. Evoked potentials correlated with severity of presenting symptoms (P = .011), age at evoked potential testing (P = .029), and presence of focal white-matter lesions on MRI (P = .049). Results of neurophysiologic testing showed no correlation with the Woodcock-Johnson Battery. Patients with classic galactosemia may have abnormal conduction along myelinated pathways that is associated with other central deficits. Myelin, which contains galactose, may be adversely affected in this inborn error of metabolism.

Brain-adrenal axis hormones are altered in the CSF of infants with massive infantile spasms.

Massive infantile spasms (MIS), a seizure disorder unique to infants, is considered an age-dependent response of the immature brain to various insults and stressors. The seizures improve with ACTH and glucocorticoids, both major components of the brain-adrenal axis. We hypothesized that CNS levels of these hormones are abnormal in infants with MIS and studied CSF from 14 infants with MIS and 13 age-matched controls by analysis for corticotropin-releasing hormone (CRH), ACTH, cortisol, and interleukin-1-beta. ACTH levels in CSF of patients were significantly lower than those of controls, but differences in cortisol levels between patients and controls were not statistically significant. CRH levels in both groups were similar and fluctuated diurnally. These results indicate an alteration of specific CNS components of the brain-adrenal axis in MIS.

Compulsive somatosensory self-stimulation inducing epileptic seizures.

Three children who had been diagnosed as having infantile spasms with major psychomotor retardation were referred for the persistence of series of spasm-like seizures, which were resistant to antiepileptic drug treatment, beyond infancy. Serial seizures were elicited by a compulsive self-stimulating behavior that was documented by long-term video-polygraphy. These behaviors implicated proprioceptive inputs: tapping on the chin in one case, flexion and external rotation of the leg with dislocation of the femur in one case, a particular posturing of the body followed by rhythmic shaking of the head in the last case. This clinical picture seems to constitute a particular type of outcome for infantile spasms and is particularly resistant to therapy.

Depressed interferon synthesis in skin fibroblasts from lung cancer patients.

Skin fibroblast cell cultures, derived from male adult lung cancer patients, an adult control population, and a newborn population were examined for their susceptibility to transformation with Kirsten murine sarcoma virus and their ability to respond to an interferon inducer (poly I.poly C). An association between sensitivity to viral transformation and induction of interferon was observed. Cultures derived from lung cancer patients demonstrated an increased sensitivity to virus transformation and a decreased ability to respond to interferon induction as compared with age-matched controls and newborns.

Rhythmic coma in children.

We describe a syndrome of rhythmic coma in children that consists of an invariant, nonreactive, diffuse cortical activity of a specific frequency, such as alpha, beta, spindle, or theta, recorded from a comatose child. We report 11 cases of children who were found to be in rhythmic coma during their acute illnesses. Their ages ranged from 2 to 15 years, and their diagnoses included encephalitis, head trauma, seizures, near drowning, brain tumors, stroke, and metabolic derangements. The specific frequency of the electroencephalographic pattern, ie, alpha, beta, spindle, or theta, did not influence the outcome. The clinical outcome appeared to depend on the primary disease process rather than the electroencephalographic finding. The prognosis of alpha-frequency rhythmic coma as well as of rhythmic coma in general was better in children than in adults. The pathophysiology in children may be similar, ie, the interruption of reticulothalamocortical pathways by metabolic or structural abnormalities, but the expression of this deafferentation may be more varied in the developing brain. Thus, we propose the term rhythmic coma as a unified concept for alpha, beta, spindle, and theta coma in children.

Depressed interferon synthesis in skin fibroblasts from lung cancer patients.

Skin fibroblast cell cultures, derived from male adult lung cancer patients, an adult control population, and a newborn population were examined for their susceptibility to transformation with Kirsten murine sarcoma virus and their ability to respond to an interferon inducer (poly I X poly C). An association between sensitivity to viral transformation and induction of interferon was observed. Cultures derived from lung cancer patients demonstrated an increased sensitivity to virus transformation and a decreased ability to respond to interferon induction as compared with age-matched controls and newborns.

Technological trends in automobiles.

Current technological trends in the automotive industry reflect many diverse disciplines. Electronics and microprocessors, new engine transmission concepts, composite and ceramic materials, and computer-aided design and manufacture will combine to make possible the creation of advanced automobiles offering outstanding quality, fuel economy, and performance. A projected "average" vehicle of the 1990's is described to illustrate the application of these new concepts.

Inhibitory effects of an aromatic retinoid (Ro 10-9359) on viral tumorigenesis.

Prophylactic treatment of hamsters and chickens with an aromatic retinoid (Ro 10-9359) inhibited Rous sarcoma virus (RSV) tumorigenesis. Retinoid administration to chickens with RSV-induced tumors resulted in tumor regression and/or confinement to the primary site. The retinoid also exerted a therapeutic effect on Shope virus papilloma development in the skin of rabbits.