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[Transcutaneous measurement of PO2 in healthy subjects and in arteriopathy patients during the exercise test].

The authors studied the variation in tcPO2 during a stress test conducted on a treadmill in normal subjects and in patients with stage I and II vascular disease according to Fontaine's classification. The tcPO2 was measured in the foot. In normal subjects, during exercise, there was an inital fluctuation in the tcPO2 which subsequently remained stable. In patients with arterial disease, the tcPO2 was variable. During the recovery phase, the tcPO2 gradually decreased to its previous level in normal subjects, but in patients with arterial disease, it abruptly fell to below its original value and then gradually returned to this value. This fall and the recovery time are related to the degree of arterial insufficiency in the limb examined. The end of the pain on effort coincides with the beginning of the increase in tcPO2. These findings, during the recovery phase, are related, according to the authors, to the oxygen debt of the muscle masses situated proximally to the point of recording.

Adult↗

Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes.

1. Experiments were designed to investigate the involvement of superoxide anions in the attenuated endothelium-dependent relaxation of the rat aorta from streptozotocin (STZ)-induced diabetic rats. 2. The endothelium-dependent relaxation responses to acetylcholine (ACh, 10(-7) M) in helical strips of the aorta precontracted with noradrenaline (NA, 5 x 10(-3) approximately 3 x 10(-7) M) were significantly decreased in STZ-induced diabetic rats. The recovery phase of the relaxation after single administration of ACh in the STZ-induced diabetic rats was more rapid than those in control vessels. 3. Preincubation of aortic strips with superoxide dismutase (SOD, 60 u ml-1) normalized the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas catalase (150 u ml-1) or indomethacin (10(-5) M) had no effects on the relaxation. 4. SOD (180 u ml-1) caused relaxation in NA precontracted aortic strips and the degree of the SOD-induced relaxation was significantly greater in diabetic aorta as compared with age-matched control vessels. 5. When the changes in mRNA expressions of Mn-SOD or Cu-Zn-SOD were observed, Mn-SOD mRNA expression was markedly decreased, and Cu-Zn-SOD was slightly decreased in diabetic aorta. 6. These results suggest that the rapid destruction of NO by superoxide anions may occur in the STZ-induced diabetic rats, and this may be due to a decrease in mRNA expression of Mn-SOD or Cu-Zn-SOD.

Analysis of Variance↗

[Propagation rate of arterial pressure waves as a function of age and physical training].

The arterial pulse wave velocity is determined to a large extent by the arterial elastic modulus. We tried to assess the importance of this parameter in cardio-vascular adaptation to exercise by measuring pulse wave velocity (c) in 45 sedentary subjects and 28 competitive cyclists whose ages ranged from 14 to 47 years. The measurements were performed at rest and during the recovery phase after ergometric exercise. At constant diastolic pressure, a positive linear relationship was demonstrated between c and age in both the sedentary and trained subjects. The slope of this relation was significantly different in the two groups. During the recovery phase, at constant diastolic pressure, a linear relationship was also established between c and the relative increase in systolic pressure in the sedentary group classified into six age subgroups. The slope of this relation increased with age. The part taken by diastolic flow velocity during exercise in the increase in c was demonstrated in 8 subjects by simultaneous Doppler ultrasonic recording of contra-lateral femoral arterial velocity. Nevertheless diastolic flow in exercise could not explain entirely the observed increase in c. An increase in arterial elasticity modulus during exercise should be postulated in order to explain the concomitant increase in arterial pulse wave velocity.

Adolescent↗

Sequential expression of transforming growth factor-beta1 by T-cells, macrophages, and microglia in rat spinal cord during autoimmune inflammation.

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in regulating inflammatory events during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Despite accumulating evidence for local expression of TGF-beta1 in the inflamed nervous system, uncertainty remains regarding its cellular source. We have investigated the temporospatial distribution of TGF-beta1 gene expression in rat spinal cord during EAE. In actively induced EAE, in situ hybridization revealed strong expression of TGF-beta1 in meningeal and perivascular mononuclear infiltrates at onset of the disease, continued expression in perivascular infiltrates and scattered mononuclear cells at maximal disease severity, and expression in scattered parenchymal cells during recovery. Double labeling studies revealed subpopulations of infiltrating T-cells to be the major source of TGF-beta1 early in the disease, followed by macrophages at peak severity and microglial cells during the recovery phase of EAE. Astrocytes and neurons did not express TGF-beta1. Quantification of mRNA by Northern blot analysis revealed that cellular expression of TGF-beta1 by T-cells, macrophages, and microglia sums up to a long-lasting elevation of TGF-beta1 mRNA extending well into the recovery phase. Our data indicate cellular diversity and suggest functional diversity of TGF-beta1 gene expression during EAE. While TGF-beta1 expressed early in the disease by T-cells may contribute to inflammatory lesion development, microglial cells may potentially contribute to recovery by expressing immunosuppressive TGF-beta1 during remission.

Adoptive Transfer↗

Activation of granulocytes in patients treated with chemotherapy.

It is well known that patients with granulocytopenia due to chemotherapy are susceptible to life-threatening infections. To determine whether or not granulocyte function is also impaired by chemotherapy, respiratory burst, CD11b and CD18 expression were analysed by flow cytometry in granulocytes from 10 patients with haematological malignancies: before and after the commencement of high-dose chemotherapy and in the recovery phase. As a comparison, the same granulocytic functions were analysed in patients treated with low-dose hydroxyurea and in healthy volunteers. The granulocytes were activated by Staphylococcus aureus and Staphylococcus epidermidis. A decreased ability to mobilize CD18 in the recovery phase was seen, but the significance of this finding must be evaluated carefully owing to the small patient number.

Antineoplastic Agents↗

[Pulse oximetry: an indicator for the closure of a tracheostome after lateral fixation of the vocal cords (cordopexy)].

The aim of the study was to establish an objective method to predict proper breathing after the closure of the tracheostomy in patients operated upon for laryngeal diplegia by lateral cordopexy. The method is non-invasive, quantitative and independent of the patient. The study covers 18 patients in whom the closure was performed after fixation of the vocal in whom it was performed prior to the operation. The arterial oxygen saturation was measured during closure using a beat-to-beat pulse oximeter and compared with the open tracheostomy, with the closed tracheostomy at rest and under stress, and finally with the closed tracheostomy in the recovery phase. The effort was continued for 5 minutes or until the patient complained of shortness of breath (3 patients). Initially the O2 saturation in these patients did not drop below 90%, but respiratory dependent saturation variations were noted. During the recovery phase, the saturation fell below 90%. The subjective declaration of "asphyxia" always preceded the variations in the O2 saturation. From this, and from the O2 saturation curves, we conclude that the cause for the reopening of the tracheostomy comes more from a circulatory problem that from hypoxemia.

Humans↗

The treatment of angina pectoris with the new beta-receptor blocker carteolol. Results of a controlled trial in comparison with pindolol.

This trial comprised 40 patients with angina pectoris and reproducible ischaemic ST segment depression in the exercise ECG. Whenever possible the diagnosis of coronary heart disease was confirmed by coronary angiography. After a preliminary 7-day placebo period, 20 of these patients were treated for 4 weeks with 5-(3-tert-butylamino-2-hydroxy-propoxy)-3, 4-dihydro-2(1H)-quinolinone hydrochloride (carteolol hydrochloride, Endak, Endak mite), a nonselective beta-receptor blocker, having adrenergic properties (ISA) up to 30 times more powerful than those of propranolol. The trial was double-blind and randomized; standard medication (pindolol) was given to the controls. In general, the results obtained with carteolol--and also with pindolol--may be regarded as "good" or "very good". The average weekly incidence of anginal attacks fell from 6 to 4 (p less than 0.05). Carteolol produced a definite decrease in ST segment depression during exercise, at the end of exercise and in the recovery phase (p less than 0.05). The same was true for the patients treated with pindolol. There was no statistically significant difference between the treatment groups. Pulse rate and systolic blood pressure--measured before exercise and at the end of the recovery phase--did not change; however, readings made at the end of exercise showed a significant decrease (p less than 0.05). Diastolic pressure remained essentially unaltered. There were no changes in the chest radiograph or resting ECG. Laboratory results remained unchanged in both groups. In one patient of each group treatment needed to be discontinued because of dyspnoea, mainly during exercise. This reaction could probably be related to the beta-blocker therapy. The overall response to treatment, as assessed by the physician conducting the trial, was "good" or "very good" in 75% of the patients receiving carteolol and in 70% of those receiving pindolol. 70% of the patients who had received carteolol assessed the therapeutic result as "good" or "very good"; in the pindolol group 55% made the same judgment.

Adult↗

Modulation of mitochondrial transcription in response to mtDNA depletion and repletion in HeLa cells.

The steady-state amounts of mitochondrial transcripts and transcription proteins were analyzed during mtDNA depletion and subsequent repletion to gain insight into the regulation of human mitochondrial gene expression. As documented previously, HeLa cells depleted of mtDNA via treatment with ethidium bromide (EB) were found to contain reduced steady-state levels of the mitochondrial transcription factor h-mtTFA. When partially mtDNA-depleted cells were cultured in the absence of EB, h-mtTFA recovered to normal levels at a significantly slower rate than mtDNA. Human mtRNA polymerase exhibited a similar depletion-repletion profile, suggesting that the mitochondrial transcription machinery is coordinately regulated in response to changes in mtDNA copy number. Newly synthesized mitochondrial transcripts were detected early in the recovery phase, despite the fact that mtDNA, h-mtTFA and h-mtRNA polymerase were simultaneously depleted. Although delayed relative to mtDNA, the amounts of h-mtTFA and h-mtRNA polymerase sharply increased during the later stages of the recovery phase, which was accompanied by accelerated rates of transcription and mtDNA replication. Altogether, these data indicate that when mtDNA copy number is low, it is beneficial to prevent accumulation of mitochondrial transcription proteins. In addition, h-mtTFA and h-mtRNA polymerase are either normally present in excess of the amount required for transcription or their activity is up-regulated to ensure continued expression and transcription-dependent replication of the mitochondrial genome during mtDNA-depleted states.

DNA Replication↗

Antibody responses to mycobacterial and self heat shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis.

Many autoimmune diseases are believed to involve primarily T cell-mediated effector mechanisms. There is increasing realization, however, that Abs may also play a vital role in the propagation of T cell-driven disorders. In this study, on the rat adjuvant-induced arthritis (AA) model of human rheumatoid arthritis, we examined the characteristics of serum Ab response to mycobacterial heat shock protein (hsp) 65 (Bhsp65), self (rat) hsp65 (Rhsp65), and linear peptides spanning these two molecules. The AA-resistant WKY (RT.1(l)) rat responded to the heat-killed Mycobacterium tuberculosis immunization with a rapid burst of Abs to both Bhsp65 and Rhsp65. These Abs reacted with numerous peptide epitopes; however, this response was reduced to a few epitopes with time. On the contrary, the susceptible Lewis (RT.1(l)) rat developed a relatively lower Ab response to Bhsp65, and Abs to Rhsp65 did not appear until the recovery from the disease. The Ab response in Lewis rats diversified with progression of AA, and there was an intriguing overlap between the repertoire of Bhsp65-reactive B and T cells during the recovery phase of AA. Nonetheless, subsets of the repertoire of the late Abs in both rat strains became focused on the same epitope regions of Bhsp65 and Rhsp65. The functional relevance of these Abs was evident from the results showing that sera from recovery phase Lewis or WKY rats, but not that of naive rats, afforded protection against subsequent AA. These results are of significance in further understanding of the role of humoral immunity in the pathogenesis of autoimmune arthritis.

Animals↗

On- and off-responses of heart rate to exercise - relations to heart rate variability.

During physical exercise, heart rate (HR) increases by parasympathetic withdrawal and increase of sympathetic activity to the heart. HR variability (HRV) in time and frequency domains provides information about autonomic control of the cardiovascular system. Non-linear analysis using the Poincaré plot method is able to reveal supplementary information about cardiac autonomic control. The aim of this study was to determine the association between HRV parameters, the initial increase of HR at the onset of exercise (on-response) and HR decrease in the recovery phase after acute exercise (off-response). HR was continuously monitored in 17 healthy male subjects (mean age: 20.3 +/- 0.2 (SEM) years) at rest (25 min supine; 5 min standing), during exercise (8 min of step test at 70% of maximal power output) and in the recovery phase (30 min supine). HRV analysis in time and frequency domains and evaluation of the Poincaré plot measures (length, widths) were performed on selected segments of HR time series. HR on- and off-responses were quantified using an exponential curve fitting technique. The time constants T(on) and T(off), representing the rate of on- and off-responses to exercise, were computed. Postexercise HRV indices and time constant of on-response - T(on) - to exercise were negatively correlated. From preexercise HRV indices, only Poincaré plot parameters were correlated with T(on). No correlation between HRV indices and parameters of off-response was found. In conclusion, preexercise HRV parameters are not closely correlated with the rate of cardioacceleration at the onset of exercise and cannot predict the rate of HR recovery. On the other hand, postexercise HRV parameters are related to the rate of initial adjustment of HR to exercise referring to the importance of rapid HR on-response for a faster recovery after exercise.

Adult↗

Prolonged negative feedback suppression after estradiol administration: proposed mechanism of eugonadal secondary amenorrhea.

The finding of normal gonadotropin and estradiol levels in eugonadal women with secondary amenorrhea suggests a disordered feedback relationship of the hypothalamic-pituitary-ovarian axis. To identify possible defects in negative and positive feedback, we compared the effects of five daily injections of 17 beta-estradiol (E2) in 13 normal women and 11 eugonadal patients with absent cyclic menses. The suppression phase of negative feedback was normal, as LH and FSH were similarly lowered in both groups on day 3. Continued LH (P less than 0.01) and FSH (P less than 0.02) inhibition on day 10 of the protocol, 5 days after the last E2 injection, indicated a defect in the recovery phase of negative feedback in the 11 amenorrheic women. In the 4 patients studied gonadotropin suppression persisted for 3 weeks, E2 did not blunt pituitary responsiveness to GnRH in the amenorrheic women, suggesting a central nervous system site for prolonged gonadotropin inhibition. Nine normal but only 2 amenorrheic women X2 = 4.15; P less than 0.05) exhibited a positive feedback increase in LH on days 4-6. We propose that a defect in the recovery phase of negative feedback to E2 rather than absent positive feedback may be the dominant physiological abnormality which causes secondary amenorrhea by preventing early follicular phase gonadotropin increments and follicular maturation.

Adult↗

The suppression of T cell apoptosis influences the severity of disease during the chronic phase but not the recovery from the acute phase of experimental autoimmune encephalomyelitis in mice.

The elimination of T cells by apoptosis is considered to be one of the regulatory factors in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To address further the role of apoptotic T cell death in EAE, we investigated myelin oligodendrocyte glycoprotein (MOG)-induced EAE in transgenic mice overexpressing the anti-apoptotic gene, bcl-2, in T cells. During the acute phase of EAE, no significant difference was observed in the clinical course, pathology and T cell response to MOG between bcl-2 transgenic mice and wild-type littermates. While the recovery from the first attack of EAE was not impaired in the bcl-2 transgenic mice, a more severe disease was observed during the chronic phase of the disease even though T and B cell responses to MOG were comparable to those of wild-type littermates. A flow cytometric analysis by Annexin V showed a significant decrease of apoptotic T cells in the central nervous system (CNS) of the bcl-2 transgenic mice with EAE compared with controls during the chronic as well as the acute phase of disease. These results suggest that while T cell apoptosis in the CNS may play a regulatory role in EAE, the spontaneous recovery from acute EAE cannot solely be explained by T cell apoptosis.

Acute Disease↗

Inhibition of CFU-G formation by human serum during granulopoiesis after chemotherapy: purification of CFU-G-inhibitory factor and its activities.

We found that the sera obtained from patients with acute leukemia (AL) in complete remission or malignant lymphoma (ML) during the recovery phase after chemotherapy completely inhibited the GCT-CM-stimulated growth of allogenic and autologous bone marrow colonies in vitro. We investigated 5 AL patients and 6 ML patients from whom blood samples were taken either every day or every 6 h during the recovery phase after chemotherapy. Colony-inhibitory sera, were detected in all patients, more frequently when the peripheral leukocyte count recovered to about 2,500 x 10(6)/l, but then transiently and at intervals. The colony-inhibitory factor purified from the inhibitory sera inhibited the growth of G-CSF-responsive colonies in a dose-dependent manner, but no effect on the growth of GM-CSF-responsive colonies, CFU-E, or BFU-E, was observed. These results suggest that this factor may play a role in regulating granulopoiesis by inhibiting the differentiation of G-CSF-responsive precursor cells.

Acute Disease↗

[Cardiovascular adaptation to the stress test in subjects with Cooley's disease].

Thalassaemia major determines an impaired effort tolerance because of a condition of severe anaemia, progressive left ventricular dysfunction, pulmonary circulation compromise. The aim of our study is to evaluate haemodynamic response to exercise in thalassaemic patients without clinical features of heart failure. We have selected 13 patients affected by thalassaemia major (Thal+; 10-18 years). Each patient was transfused when haemoglobin values were < 9-9.5 g/dl and was treated with desferrioxamine (40 mg/kg sc) when serum ferritin values were > 2,000 ng/ml. Thal+ patients were compared with normal subjects (Thal- 10-16 years). No patient assumed hypotensive therapy, no had familiar history of hypertension. Both groups have undergone an ergometric stress test at the cycloergometer, with increase of 25 W every 2 min, up to the reaching of the maximum age-related heart rate, or up to muscle exhaustion or unbearable dyspnea, followed by a 10 min recovery phase. The following parameters were taken in consideration: systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), the product of the heart rate by the systolic blood pressure (DP), at rest, at the maximum common work (MCW), at maximum stress and in the recovery phases. At rest, only DP showed significant differences between the two groups: in Thal+ patients higher than in Thal- (p = 0.045). At the MCW, Thal+ patients had SBP (p = 0.019), DBP (p = 0.01), HR (p = 0.035) and DP (p = 0.003) higher than Thal- patients. At maximum stress only DBP showed significant differences in Thal+ patients (p = 0.019), although Thal+ patients achieved lower levels of workload (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

U wave inversion during attacks of variant angina.

Sequential 12 lead electrocardiograms were recorded during angina pectoris induced by ergonovine maleate in 38 patients with variant angina. Transient U wave inversion was observed in 17 patients with ST segment elevation in anterior chest leads, but in only three of 21 patients with ST segment elevation in the inferior leads associated with right coronary artery spasm. In the 17, all of whom had spasm of the left anterior descending coronary artery, the sensitivity of ST segment elevation in V5 was only 41%, and that of U wave inversion 71%. U wave inversion without ST segment elevation occurred during attacks in 35% of patients. During the recovery phase, the sensitivity of U wave inversion was 82% in V4 and 65% in V5, though ST segment elevation was absent in both V4 and V5. Thus, inverted U waves without ST segment elevation often appear in marginal ischaemic zones or during the time of recovery from temporary ischaemia. Detection of inverted U waves should aid in the diagnosis of variant angina when only lead V5 is used as a monitor and when electrocardiograms are recorded only during the recovery phase.

Adult↗

Cardiac surgery and women.

Coronary heart disease is just as serious a problem for women as it is for men, yet historically women have been significantly underrepresented in research studies related to the disease and treatment options, including cardiac surgery. Cardiac surgery is a proven therapy for the management of coronary heart disease in women. Research addressing the physical, psychosocial, and emotional issues women face during the preoperative, postoperative, and recovery phases of surgery is limited. Nurses play a pivotal role in the education and management of women undergoing cardiac surgery and need to be aware of unique issues related to the experience. This article reviews the literature pertaining to women's issues during the perioperative and recovery phases of cardiac surgery.

Cardiac Surgical Procedures↗

[Arterial pressure in obese subjects during ergometric stress test and recovery].

In obesity, the systemic resistances (SR) are reduced while the blood volume is increased. The rise of cardiac output (CO), stress-induced, produces an increase in blood pressure (BP), as an hypertensive behavior of the stress-response. The aim of our study is to evaluate if, in obese subjects, the considerable increase of BP is more related to the rise of CO than to the rise of SR. For this reason we studied the behavior of BP through indexes derived from the ratio of SBP values at the 1st, 3rd, 5th, 10th minutes of the recovery by the SBP value at the acme of stress. These indexes are under neurovegetative control, and were shown to be impaired in hypertensive pts. The results of ergometric stress test (EST) of 37 obese subjects (Ob+) (27 males and 10 females, mean age 46.2 +/- 7.3 years), determined according to Lorentz's formula, was compared with the parameters deduced from the EST of 18 normal subjects (Ob-) (13 males and 5 females, mean age 36.7 +/- 8.5). The exercise showed an increase, more pronounced in Ob+ subjects, of SBP and DBP, and this also persisted in the recovery phase. Although BP was significantly higher in the Ob+group, the SBP indexes did not differ in the two groups. Then, from these data it can be deduced that, although during EST in obese subjects there is an absolute increase of BP and this persists in the recovery phase, the behavior of this parameter probably cannot be related to alteration of neurovegetative system as demonstrated by the normal SBP indexes.

Adult↗

Kinetics of circulating haematopoietic progenitors during chemotherapy-induced mobilization with or without granulocyte colony-stimulating factor.

Kinetics of circulating haematopoietic progenitors was analysed during chemotherapy- or chemotherapy plus granulocyte colony-stimulating factor (G-CSF)-induced mobilization of peripheral blood stem cells. Circulating progenitors including colony-forming unit granulocyte/macrophage (CFU-GM), burst forming-unit erythroid (BFU-E) and multilineage colony forming unit (CFU-Mix) were studied serially on alternate days during a recovery phase from chemotherapy for consolidation of complete remission. In 18 patients with acute leukaemia, 27 courses of consolidation chemotherapy were performed with a combination of an intermediate-dose cytosine arabinoside with etoposide (Ara-C/Etop) or mitoxantron (Ara-C/Mit). G-CSF (5 micrograms/kg) was administered during the recovery phase in 6/14 courses with Ara-C/Etop and in 4/13 courses with Ara-C/Mit. G-CSF induced a significant and synchronized increase of circulating CFU-GM, BFU-E and CFU-Mix by more than 4-fold at their peaks. The peak of CFU-GM was significantly correlated with that of both BFU-E and CFU-Mix, irrespective of additional G-CSF mobilization. G-CSF also produced a significant increase of monocytes in a synchronized fashion with an increase of circulating CFU-GM. Interestingly, peripheral blood monocytes spontaneously produced high concentrations of IL-6; a significant correlation was observed between absolute monocyte counts and plasma levels of IL-6 or peak levels of CFU-GM. These observations indicate that the addition of G-CSF to chemotherapy-induced mobilization can facilitate further expansion of a blood progenitor pool during the haematopoietic recovery, probably through the stimulation of monocytes to proliferate and to induce their monokine production such as IL-6. The data also suggest that absolute monocyte counts may be a useful indicator to predict the peak of circulating progenitors for collecting autologous blood stem cells.

Adolescent↗