Lactate exchange and removal abilities in sickle cell patients and in untrained and trained healthy humans.

Arterial blood lactate concentrations obtained on seven black males with hemoglobin sickle cell disease (SC) before, during, and after graded bicycle exercise up to exhaustion were compared with those of seven untrained (HU) and seven trained (HT) healthy males of the same ethnic origin. Lactate recovery curves were fitted by a biexponential time function consisting of a rapidly increasing and a slowly decreasing component. Higher work rates were reached by the HU and HT than by the SC group. Blood lactate rose distinctly over the corresponding preexercise resting values after the 25-, 50-, and 100-W exercise steps for the SC, HU, and HT groups, respectively. The arterial oxygen content was significantly lower for the SC than for the HU group at rest and at the end of exercise. The velocity constants of the slowly decreasing component of the lactate recovery curves were similar for the SC, HU, and HT groups despite the fact that they cycled up to different absolute work rates. The velocity constant of the rapidly increasing component was significantly higher for the HT. In terms of the functional meaning given to these constants and in view of their inverse relationship with absolute work rate (Freund et al. J. Appl. Physiol. 61: 932-939, 1986), these results indicate that, relative to the HU, the HT and the SC display improved and impaired abilities, respectively, to exchange and to remove lactate.

Twenty-four-hour plasma cortisol and prolactin in human African trypanosomiasis patients and healthy African controls.

We have previously demonstrated that human African trypanosomiasis (sleeping sickness) at the stage of meningoencephalitis results in a major disruption of the circadian rhythmicity of sleep and wakefulness that is proportional to the severity of the disease. This paper examines the corresponding 24-hourly secretion in cortisol and prolactin and compares it with the hourly distribution of sleep composition in infected patients and healthy African subjects. The secretion of cortisol in humans follows a circadian rhythm relatively independent of the sleep-wake cycle, whereas that of prolactin exhibits fluctuations over the 24-hr day that are strongly related to the sleep-wake cycle. After the clinical classification of the patients according to the severity of the disease, hourly blood samples were taken over 24 hr via an indwelling catheter. Plasma cortisol and prolactin were analyzed by radioimmunoassay, and the variations in the hourly concentrations were analyzed for the presence of a potential 24-hr rhythm (circadian). All of the healthy African subjects showed significant circadian rhythms in both cortisol and prolactin secretion, similar to data on humans from temperate regions, and a sleep-related anamnestic afternoon peak of prolactin. Major disruptions in the circadian rhythms of plasma cortisol and prolactin were found in the three patients with the most severe illness, in contrast to the four who were less severely ill and the healthy controls. Thus, it appears that as the disease progresses in severity, major disruptions begin to occur in body circadian rhythms, not only in the sleep-wake cycle as reported elsewhere, but also in cortisol and prolactin secretion, suggesting that sleeping sickness affects the circadian timing system.

Proteinuria in sickle cell trait and disease: an electrophoretic analysis.

Using ultrafiltration and SDS-PAGE, abnormal urinary protein excretion was found in 25.4% of 189 persons with sickle cell disease and trait, but none of 72 controls. Based upon molecular weight of urinary proteins, underlying renal lesions were classified as glomerular, tubular, or both. Altered protein excretion appeared at an early age, was more abnormal in older subjects, and was related to the severity of sickle cell disease (SS greater than SC = S/beta Thal greater than AS). Since none of the subjects had yet developed clinically significant renal disease, SDS-PAGE may permit early detection of patients who require careful follow-up or aggressive therapy.

Cardiorespiratory and metabolic responses to exercise in HbSC sickle cell patients.

PURPOSE: Relative to healthy control individuals with normal hemoglobin (Hb), patients carrying the double heterozygous form of sickle cell disease (HbSC) display an impaired oxygen transport capacity. The present study was undertaken to determine the influence of the decreased oxygen availability associated with the presence of HbSC on the cardiorespiratory and metabolic responses to endurance exercise. METHODS: Eleven black men affected by the double heterozygous form of the sickle cell disease (HbSC group) and seven healthy subjects with normal Hb (HbAA group) of the same ethnic origin submitted successively to an incremental exercise test to exhaustion on a cycle ergometer for the determination of their maximal tolerated power and to a 20-min endurance exercise. RESULTS: The HbSC had a significantly lower exercise tolerance than the HbAA. During the endurance exercise, they exhibited furthermore significantly lower VO2, VCO2, and minute ventilation V(E) than the HbAA. Despite the fact that the HbSC exercised at a significantly lower mean absolute work rate than the HbAA, except for the ventilatory equivalent for CO2 (V(E)/VCO2), which was higher (P < 0.001) in the HbSC group, the other parameters recorded during the 20-min endurance exercise (heart rate, arterial PaO2, PaCO2, pH, lactate, and VE/VO2, the ventilatory equivalent for O2) and during the subsequent recovery (blood lactate) were similar for both groups. CONCLUSION: The study underscores the importance of considering relative work rate as well as absolute work rate to arrive at a correct interpretation of exercise and recovery data. The results give evidence that the modifications of homeostasis brought into play by exercise were shifted toward distinctly lower absolute work rates in HbSC patients.

Disruptions in the secretion of cortisol, prolactin, and certain cytokines in human African trypanosomiasis patients.

It has been shown previously that sleeping sickness at the stage of meningoencephalitis manifests itself as a significant disturbance in the circadian rhythm of sleep-wakefulness. The objective of the current study was to examine the extent of circadian disruption in infected patients by measuring 24 hours patterns of plasma cortisol, an example of a classical circadian rhythm relatively independent of sleep, and prolactin, a primarily sleep-related rhythm. Plasma levels of certain cytokines were also measured to examine the immunopathogenesis of human African trypanosomiasis. An attempt was made to relate any circadian disruptions to the severity of the disease. The three most advanced patients demonstrated circadian disruptions in cortisol, prolactin and sleep-wake rhythms. The prime cytokine factor that correlated with the progression of the disease in humans was interferon-gamma, levels being 7- to 12-fold higher in the patients without any circadian rhythms. Our findings support the hypothesis that human African trypanosomiasis induces selective changes in the suprachiasmatic nucleus, important as a pacemaker for biological rhythms, resulting in disruptions of circadian rhythmicity in advanced stages of the disease.

[Blood levels of protein markers of inflammation and nutrition in the meningo-encephalitis phase of human African trypanosomiasis]. / Valeurs sériques des marqueurs protéiques de l'inflammation et de la nutrition dans la phase méningo-encéphalitique de la trypanosomose humaine africaine.

Two acute phase proteins; C-reactive protein and acid alpha 1-glycoprotein and three nutritional markers; prealbumin, retinol binding protein and transferrin have been evaluated in 8 patients suffering from trypanosomiasis in meningoencephalitic state and compared to those obtained from 15 normal control subjects. Findings show a markly decrease of nutritional markers without change of sera acute phase proteins. We concluded that in meningo-encephalitic state of human african trypanosomiasis, denutrition was a major biological or clinical feature in association with lymphoid cells stimulation as revealed by beta 2-M levels.

[Inflammatory reaction markers and nutritional markers in HIV infection]. / Marqueurs de la réaction inflammatoire et marqueurs nutritionnels au cours de l'infection à VIH.

A protein profile has been monitored during human immunodeficiency virus (HIV) infection. The investigation concerned 60 patients suffering from acquired immunodeficiency syndrome (AIDS), 24 asymptomatic HIV-antibody seropositive subjects and 22 healthy HIV-antibody seronegative, individuals voluntary blood donors. Data show that retinol-binding protein, thyroxin-binding prealbumin and beta 2-microglobulin are already modified in HIV infection (p less than 0.05) whereas the other protein alteration becomes apparent during AIDS. These studies demonstrate that severe, but progressive malnutrition occurs in patients with AIDS. On the other hand nutritional abnormalities can be shown to have a deleterious effect upon the disease course as revealed by increasing alpha-1-acid glycoprotein and C-reactive protein levels for 60 to 70% of patients.

[Evaluation of the inflammatory process in hepatic disorders: immunochemistry of C alpha-reactive protein and of alpha 1-acid glycoprotein]. / Evaluation du processus inflammatoire dans les atteintes hépatiques: dosage immunochimique de la protéine C alpha-réactive et de l'alpha 1-glycoprotéine acide.

C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1-GPA) two acute phase reactants, have both been monitored in patients suffering from hepatocellular diseases, compared with healthy subjects. Immunochemical findings, in hepatic amebiasis, revealed a higher incidence of increased alpha 1-GPA levels (86% of patients, as compared to 46% for CRP), whereas during liver primitive cancer and cirrhosis inverse pattern occurs. In viral chronic hepatitis, lesser perturbations were observed. In contrast, a simultaneous increase of both proteins is strong supporting evidence for the severity of disease with an unfavourable prognostic.

Lactate exchange and removal abilities in sickle cell trait carriers during and after incremental exercise.

Arterial blood lactate concentrations and pH were measured on seven black male sickle cell trait (SCT) carriers before, during and after incremental exhaustive bicycle exercise (25 W increments per minute) and compared with those of six control individuals of the same ethnic origin having a similar physical fitness level. The object of the experiment was to determine if SCT has an effect on lactate kinetics. At volitional exhaustion which was reached at a comparable overall mean absolute work rate for both groups, oxygen consumption expressed per kilogram body mass was significantly lower for the SCT carriers than for the control volunteers. Lactate concentrations were higher for the SCT carriers after the 150 W exercise step but differences reached statistical significance only at exhaustion. Concentrations were distinctly higher for the SCT group during the following 40 minutes of recovery. While there were no observable differences in blood pH between the SCT and control subjects during the exercise, this variable became significantly lower for the SCT than for the control group 8 minutes after the end of exercise. Lactate recovery curves were fitted by a biexponential time function where the two velocity constants inform on the body's overall ability to exchange and remove lactate. The ability to remove lactate was comparable for the two groups. The present results do not warrant drawing a definite conclusion on impairment of the ability to exchange lactate in the presence of SCT. However, SCT carriers are likely to produce more lactate than control subjects reaching exhaustion at similar mean absolute work rate during exhaustive incremental bicycle exercise.

Study of evoked potentials in human African trypanosomiasis.

Human African trypanosomiasis or sleeping sickness has a stage of neurological involvement characterized by the onset of diffuse meningoencephalitis with sleep disturbances and decreased wakefulness. The pathogenesis of this disease is not well understood. We studied auditory, visual, sensory, and motor evoked potentials in 16 patients with trypanosomiasis in the early stage of meningoencephalitis. In all patients, the brain-stem auditory evoked response (BAER) and the pattern-reversal visual evoked response (PVER) were normal. On the other hand, abnormalities of the somatosensory evoked response (SSER) or the motor evoked response (MER) were found in only five cases; however, their relationship to the illness could not be definitely confirmed. The study results indicate that the evaluated pathways were essentially intact, in particular at the level of the brain-stem in the early stage of the disease. Sleep disturbances and decreased wakefulness noted at this stage were thus linked more closely to functional involvement at the level of the sleep centres than to any detectable specific anatomic lesion.