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Biomedical subjects

B Grassi

Publications and source records attributed to B Grassi.

At least 19 recordsLinked to original sources
PubMed2006

High plasma creatine kinase: review of the literature and proposal for a diagnostic algorithm.

The condition of persistently high plasma CK levels is frequently encountered in asymptomatic patients with normal neurological examination. This condition may be the unique manifestation of several neuromuscular disorders, whose diagnosis is now possible using new diagnostic techniques. However, even if these patients are intensely investigated, specific diagnoses are not always forthcoming. Because of the lack of a widely accepted diagnostic protocol, hyperCKaemia in asymptomatic subjects is a potentially difficult clinical problem. In this paper we review the literature on conditions associated with variations in plasma CK levels and the literature on investigations carried out in asymptomatic persons with high CK to identify neuromuscular diseases. In the light of these data, and the deliberations of a working group of the Italian Association of Myology, we propose a diagnostic algorithm to guide the diagnostic work-up of persons presenting with persistently high levels of plasma CK. This algorithm has been discussed and approved by the Committee of the Italian Association of Myology.

Algorithms↗
PubMed2004

Immediate (overnight) switching from carbamazepine to oxcarbazepine monotherapy is equivalent to a progressive switch.

This study compared immediate (overnight) and progressive switching to oxcarbazepine monotherapy in patients with partial seizures unsatisfactorily treated with carbamazepine monotherapy. Patients were randomised to either an overnight (n = 140) or a progressive switch (n = 146) from carbamazepine to oxcarbazepine monotherapy at a dose ratio of 1:1.5. The difference between the two switch groups in the mean monthly seizure frequency supported the equivalence of overnight and progressive switching (difference of 0.02 excluding outliers; 95% confidence interval (CI) -0.74, 0.78). Following the switch from carbamazepine to oxcarbazepine, there was a reduction in median monthly seizure frequency in both the overnight group (from 1.5 to 0; P = 0.0005) and the progressive group (from 1.0 to 0.4; P = 0.003). The proportion of seizure-free patients increased from 38 to 51% (P = 0.002) and 39 to 49% (P = -0.01) in the overnight and progressive groups, respectively. In addition, the proportion of patients experiencing no clinically significant adverse events did not differ between the two switch methods (difference of 2.5; 95% CI -4.1, 9.0). For patients who are unsatisfactorily treated with carbamazepine monotherapy, overnight switch to oxcarbazepine monotherapy is as effective and well tolerated as a progressive switch, therefore allowing simple and flexible individualised treatment. Switching to oxcarbazepine monotherapy appears to be beneficial for patients who are unsatisfactorily treated with carbamazepine monotherapy, independently of the switch method used.

Adolescent↗
PubMed2001

Power and peak blood lactate at 5050 m with 10 and 30 s 'all out' cycling.

Anecdotal observations suggest that the reduction in peak lactate accumulation in blood ([La]b peak) after exhausting exercise, in chronic hypoxia vs. normoxia, may be related to the duration of the exercise protocol, being less pronounced after short supramaximal exercise than after incremental exercise (IE) lasting several minutes. To test this hypothesis, six healthy male Caucasians (age 36.8 +/- 7.3, X +/- SD) underwent three exercise protocols on a cycle ergometer, at sea level (SL) and after 21 +/- 10 days at 5050 m altitude (ALT): (1) 10 s, (2) 30 s 'all out' exercise and (3) IE leading to exhaustion in approximately 20-25 min. 'Average' power output (P) was calculated for 10 or 30 s 'all out'; maximal power output (Pmax) was determined for IE. Lactate concentration in arterialized capillary blood ([La]b) was measured at rest and at different times during recovery; the highest [La]b during recovery was taken as [La]b peak. No significant differences in P were observed between SL and ALT, for either 10 or 30 s 'all out' exercise; Pmax during IE was significantly lower at ALT than at SL. [La]b peak after 10 s 'all out' was unaffected by chronic hypoxia (7.0 +/- 0.9 at ALT vs. 6.3 +/- 1.8 mmol x L(-1) at SL). After 30 s 'all out' the [La]b peak decrease, at ALT (10.6 +/- 0.6 mmol x L(-1)) vs. SL (12.9 +/- 1.4 mmol x L(-1)), was only approximately 50% of that observed for IE (6.7 +/- 1.6 mmol x L(-1) vs. 11.3 +/- 2.8 mmol x L(-1)). Muscle power output and blood lactate accumulation during short supramaximal exercise are substantially unaffected by chronic hypoxia.

Adult↗
PubMed2001

Regulation of oxygen consumption at exercise onset: is it really controversial?

The conflicting hypotheses on the limiting factors for skeletal muscle VO2 on-kinetics might be reconciled in a unifying scenario. Under "normal" conditions, during transitions to moderate intensity exercise, the limiting factor appears to be an inertia of oxidative metabolism. During transitions to exercise of higher metabolic intensity, O2 delivery could play a relatively minor but significant role as a limiting factor.

Anaerobic Threshold↗
PubMed2000

Skeletal muscle: master or slave of the cardiovascular system?

Skeletal muscle and cardiovascular system responses to exercise are so closely entwined that it is often difficult to determine the effector from the affector. The purpose of this manuscript and its companion papers is to highlight (and perhaps assist in unraveling) the interdependency between skeletal muscle and the cardiovascular system in both chronic and acute exercise. Specifically, we elucidate four main areas: 1) how a finite cardiac output is allocated to a large and demanding mass of skeletal muscle, 2) whether maximal muscle oxygen uptake is determined peripherally or centrally, 3) whether blood flow or muscle metabolism set the kinetic response to the start of exercise, and 4) the matching of structural adaptations in muscle and the microcirculation in response to exercise. This manuscript, the product of an American College of Sports Medicine Symposium, unites the thoughts and findings of four researchers, each with different interests and perspectives, but with the common intent to better understand the interaction between oxygen supply and metabolic demand during exercise.

Adaptation, Physiological↗
PubMed2000

Skeletal muscle VO2 on-kinetics: set by O2 delivery or by O2 utilization? New insights into an old issue.

Recent work conducted by our group has expanded knowledge on some basic issues related to pulmonary and skeletal muscle O2 uptake (VO2) on-kinetics. We demonstrated that, in exercising humans during transitions from unloaded pedaling to loaded pedaling below the ventilatory threshold, alveolar VO2 on-kinetics can be taken as a rather close approximation of skeletal muscle VO2 on-kinetics. Experiments conducted on the isolated in situ dog gastrocnemius preparation have shown that, during transitions from rest to contractions corresponding to approximately 70% of the muscle peak VO2, convective O2 delivery to muscle, intramuscular blood flow (Q) versus VO2 maldistribution, and peripheral O2 diffusion are not limiting factors for skeletal muscle VO2 on-kinetics. The latter, therefore, appears to be mainly determined by an intrinsic inertia of skeletal muscle oxidative metabolism, possibly related to acetyl group availability within mitochondria, to regulatory effects on intracellular respiration related to phosphocreatine splitting, and/or to other still not precisely identified control mechanism(s). Evidence from the literature suggests that the limiting factors for skeletal muscle VO2 on-kinetics may vary according to the intensity of muscular contractions or of exercise.

Animals↗
PubMed2000

Role of convective O(2) delivery in determining VO(2) on-kinetics in canine muscle contracting at peak VO(2).

A previous study (Grassi B, Gladden LB, Samaja M, Stary CM, and Hogan MC, J Appl Physiol 85: 1394-1403, 1998) showed that convective O(2) delivery to muscle did not limit O(2) uptake (VO(2)) on-kinetics during transitions from rest to contractions at approximately 60% of peak VO(2). The present study aimed to determine whether this finding is also true for transitions involving contractions of higher metabolic intensities. VO(2) on-kinetics were determined in isolated canine gastrocnemius muscles in situ (n = 5) during transitions from rest to 4 min of electrically stimulated isometric tetanic contractions corresponding to the muscle peak VO(2). Two conditions were compared: 1) spontaneous adjustment of muscle blood flow (Q) (Control) and 2) pump-perfused Q, adjusted approximately 15-30 s before contractions at a constant level corresponding to the steady-state value during contractions in Control (Fast O(2) Delivery). In Fast O(2) Delivery, adenosine was infused intra-arterially. Q was measured continuously in the popliteal vein; arterial and popliteal venous O(2) contents were measured at rest and at 5- to 7-s intervals during the transition. Muscle VO(2) was determined as Q times the arteriovenous blood O(2) content difference. The time to reach 63% of the VO(2) difference between resting baseline and steady-state values during contractions was 24.9 +/- 1.6 (SE) s in Control and 18.5 +/- 1.8 s in Fast O(2) Delivery (P < 0.05). Faster VO(2) on-kinetics in Fast O(2) Delivery was associated with an approximately 30% reduction in the calculated O(2) deficit and with less muscle fatigue. During transitions involving contractions at peak VO(2), convective O(2) delivery to muscle, together with an inertia of oxidative metabolism, contributes in determining the VO(2) on-kinetics.

Animals↗
PubMed1999

Clozapine lacks previous clinical efficacy when restarted after a period of discontinuation: a case series.

No data are available in the literature about clozapine clinical efficacy when the drug is administered to schizophrenic patients who relapsed after discontinuation of long-term clozapine treatment and who had previously been responsive to the drug. In this study, three chronic schizophrenic patients are presented, who, in spite of a good clinical efficacy, decided to stop long-term clozapine treatment. Soon after their relapse they were again treated with clozapine: follow-up of these patients showed that clozapine partially lost its clinical efficacy since all three patients got worse compared with their initial clinical response.

Adult↗
PubMed1999

Differential depression of myocardial function and metabolism by lactate and H+.

The effects of both high blood H+ concentration ([H+]) and high blood lactate concentration ([lactate]) under ischemia-reperfusion conditions are receiving attention, but little is known about their effects in nonischemic hearts. Isolated rat hearts were Langendorff perfused at constant flow with media at two pH values (7.4 and 7.0) and two [lactate] (0 and 20 mM) in various sequences (n = 6/group). Coronary flow and arterial O2 content were kept constant at levels that allowed hearts to function without O2 supply limitation. We measured contractility, O2 uptake, diastolic pressure, and at the end of the protocol, tissue [lactate] and pH. Perfusion with high [lactate] raised tissue [lactate] from 5.5 +/- 0.1 to 17.5 +/- 2.6 micromol/heart (P < 0.0001), whereas decreasing the pH of the medium decreased tissue pH from 6.94 +/- 0.02 to 6.81 +/- 0.06 (P = 0.002). Heart rate was not affected by high [lactate] but was reversibly depressed by high [H+] (P = 0.004). Developed pressure declined by 20% in response to high [lactate], high [H+], and high [lactate] + high [H+] (P = 0.002). After the high-[lactate] challenge was withdrawn, pressure continued to decline. In contrast, withdrawing the high [H+] challenge allowed partial recovery. The behavior of diastolic pressure mirrored that of developed pressure. Although unaffected by high [lactate], the O2 uptake was reversibly depressed by high [H+]. This suggests higher O2 cost per contraction in the presence of high [lactate]. We conclude that for similar acute contractility depression, high [lactate] induces irreversible damage, likely at some point in the pathway of O2 utilization. In contrast, the effect of high [H+] appears reversible. These differential behaviors may have implications for heart function during heavy exercise and ischemia-reperfusion events.

Animals↗
PubMed1999

Evidence of O2 supply-dependent VO2 max in the exercise-trained human quadriceps.

Maximal O2 delivery and O2 uptake (VO2) per 100 g of active muscle mass are far greater during knee extensor (KE) than during cycle exercise: 73 and 60 ml. min-1. 100 g-1 (2.4 kg of muscle) (R. S. Richardson, D. R. Knight, D. C. Poole, S. S. Kurdak, M. C. Hogan, B. Grassi, and P. D. Wagner. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1453-H1461, 1995) and 28 and 25 ml. min-1. 100 g-1 (7.5 kg of muscle) (D. R. Knight, W. Schaffartzik, H. J. Guy, R. Predilleto, M. C. Hogan, and P. D. Wagner. J. Appl. Physiol. 75: 2586-2593, 1993), respectively. Although this is evidence of muscle O2 supply dependence in itself, it raises the following question: With such high O2 delivery in KE, are the quadriceps still O2 supply dependent at maximal exercise? To answer this question, seven trained subjects performed maximum KE exercise in hypoxia [0.12 inspired O2 fraction (FIO2)], normoxia (0.21 FIO2), and hyperoxia (1.0 FIO2) in a balanced order. The protocol (after warm-up) was a square wave to a previously determined maximum work rate followed by incremental stages to ensure that a true maximum was achieved under each condition. Direct measures of arterial and venous blood O2 concentration in combination with a thermodilution blood flow technique allowed the determination of O2 delivery and muscle VO2. Maximal O2 delivery increased with inspired O2: 1.3 +/- 0.1, 1.6 +/- 0.2, and 1.9 +/- 0.2 l/min at 0.12, 0.21, and 1.0 FIO2, respectively (P < 0.05). Maximal work rate was affected by variations in inspired O2 (-25 and +14% at 0.12 and 1.0 FIO2, respectively, compared with normoxia, P < 0.05) as was maximal VO2 (VO2 max): 1.04 +/- 0.13, 1. 24 +/- 0.16, and 1.45 +/- 0.19 l/min at 0.12, 0.21, and 1.0 FIO2, respectively (P < 0.05). Calculated mean capillary PO2 also varied with FIO2 (28.3 +/- 1.0, 34.8 +/- 2.0, and 40.7 +/- 1.9 Torr at 0.12, 0.21, and 1.0 FIO2, respectively, P < 0.05) and was proportionally related to changes in VO2 max, supporting our previous finding that a decrease in O2 supply will proportionately decrease muscle VO2 max. As even in the isolated quadriceps (where normoxic O2 delivery is the highest recorded in humans) an increase in O2 supply by hyperoxia allows the achievement of a greater VO2 max, we conclude that, in normoxic conditions of isolated KE exercise, KE VO2 max in trained subjects is not limited by mitochondrial metabolic rate but, rather, by O2 supply.

Adult↗
PubMed1999

Respiratory energetics during exercise at high altitude.

The purpose of this study was to assess the effect of high altitude (HA) on work of breathing and external work capacity. On the basis of simultaneous records of esophageal pressure and lung volume, the mechanical power of breathing (Wrs) was measured in four normal subjects during exercise at sea level (SL) and after a 1-mo sojourn at 5,050 m. Maximal exercise ventilation (VEmax) and maximal Wrs were higher at HA than at SL (mean 185 vs. 101 l/min and 129 vs. 40 cal/min, respectively), whereas maximal O2 uptake averaged 2.07 and 3.03 l/min, respectively. In three subjects, the relationship of Wrs to minute ventilation (VE) was the same at SL and HA, whereas, in one individual, Wrs for any given VE was consistently lower at HA. Assuming a mechanical efficiency (E) of 5%, the O2 cost of breathing at HA and SL should amount to 26 and 5.5% of maximal O2 uptake, whereas for E of 20% the corresponding values were 6.5 and 1.4%, respectively. Thus, at HA, Wrs may substantially limit external work unless E is high. Although at SL VEmax did not exceed the critical VE, at which any increase in VE is not useful in terms of body energetics even for E of 5%, at HA VEmax exceeded critical VE even for E of 20%.

Adult↗
PubMed1999

Blood lactate accumulation and muscle deoxygenation during incremental exercise.

Near-infrared spectroscopy (NIRS) could allow insights into controversial issues related to blood lactate concentration ([La](b)) increases at submaximal workloads (). We combined, on five well-trained subjects [mountain climbers; peak O(2) consumption (VO(2peak)), 51.0 +/- 4.2 (SD) ml. kg(-1). min(-1)] performing incremental exercise on a cycle ergometer (30 W added every 4 min up to voluntary exhaustion), measurements of pulmonary gas exchange and earlobe [La](b) with determinations of concentration changes of oxygenated Hb (Delta[O(2)Hb]) and deoxygenated Hb (Delta[HHb]) in the vastus lateralis muscle, by continuous-wave NIRS. A "point of inflection" of [La](b) vs. was arbitrarily identified at the lowest [La](b) value which was >0.5 mM lower than that obtained at the following. Total Hb volume (Delta[O(2)Hb + HHb]) in the muscle region of interest increased as a function of up to 60-65% of VO(2 peak), after which it remained unchanged. The oxygenation index (Delta[O(2)Hb - HHb]) showed an accelerated decrease from 60- 65% of VO(2 peak). In the presence of a constant total Hb volume, the observed Delta[O(2)Hb - HHb] decrease indicates muscle deoxygenation (i.e., mainly capillary-venular Hb desaturation). The onset of muscle deoxygenation was significantly correlated (r(2) = 0.95; P < 0.01) with the point of inflection of [La](b) vs., i.e., with the onset of blood lactate accumulation. Previous studies showed relatively constant femoral venous PO(2) levels at higher than approximately 60% of maximal O(2) consumption. Thus muscle deoxygenation observed in the present study from 60-65% of VO(2 peak) could be attributed to capillary-venular Hb desaturation in the presence of relatively constant capillary-venular PO(2) levels, as a consequence of a rightward shift of the O(2)Hb dissociation curve determined by the onset of lactic acidosis.

Acidosis, Lactic↗
PubMed1999

Spatial working memory in asymptomatic HIV-infected subjects.

Many clinical and research findings converge to indicate that frontal lobe, basal ganglia, and related neuronal connections are primarily involved in human immunodeficiency virus (HIV) infection; frontal lobe, mainly the prefrontal cortex, has a specialized role in working memory processes. This study focused on neuropsychological evaluation of the spatial component of working memory in a sample of 34 asymptomatic HIV-infected subjects as compared with 34 age- and sex-matched seronegative control subjects. A computer-administered test assessing spatial working memory was used for the neuropsychological evaluation. The findings did not show any spatial working memory impairment during the asymptomatic phase of HIV infection.

Adult↗
PubMed1998

The effectiveness and tolerability of epoetin alfa in patients with multiple myeloma refractory to chemotherapy.

Anemia is a frequent complication of multiple myeloma, becoming chronic in patients who are resistant to chemotherapy. This randomized, parallel, controlled multicenter study (71 patients receiving concomitant chemotherapy) evaluated the efficacy and safety of epoetin alfa in improving anemia and eliminating the need for transfusions in multiple myeloma patients refractory to conventional first- or second-line chemotherapy. Forty patients were treated with subcutaneous epoetin alfa (150 IU/kg per dose, increasing to 300 IU/kg per dose, every 3 weeks) for 6 months, and 31 entered a control group. The epoetin alfa group had a significantly (P < or = 0.001) greater percentage of patients (75% vs. 21%) with increases in hemoglobin levels and/or reduced transfusion requirements. In 44 non pre-transfused patients (20 controls, 24 in the epoetin alfa group), the mean increase in hemoglobin was significantly (P < or = 0.0001) greater in the epoetin alfa group (+2.1 vs. -0.2 g/dl). Increases in hematocrit and red blood cells were also significantly (P < or = 0.0001) greater in epoetin alfa-treated patients, with corresponding reductions in transfusion requirement. In the 27 pre-transfused patients (11 controls, 16 in the epoetin alfa group), there was a trend towards reduced transfusional need in epoetin alfa-treated patients. Thus, in patients with multiple myeloma refractory to chemotherapy epoetin alfa is a well-tolerated treatment which improves anemia in non pre-transfused patients and appears to reduce transfusion need in those previously transfused.

Aged↗
PubMed1998

Cytokines production in chronic schizophrenia patients with or without paranoid behaviour.

1. Several immunological abnormalities have been found in schizophrenia but their significance still remains largely unknown. In this study the authors analyzed mitogen-stimulated interleukin (IL)-2, Interferon gamma (IFN)-gamma and IL-10 (type 2 cytokine) production in a sample of 37 chronic schizophrenic patients as compared with a sample of 40 age and sex-matched controls with the aim to evaluate whether patients belonging to different diagnostic subtypes (i.e. paranoid patients vs non paranoid patients) could be immunologically different from each other. 2. The findings indicate that paranoid patients produce less IL-10 than the others and thus, from an immunological viewpoint, they are more similar to healthy controls. 3. Furthermore, neuroleptic medications were observed to differently affect IL-2 production; this preliminary finding might stimulate further studies aiming to get a link between different drug profile of action both in terms of clinical and receptorial profile and different immunological effects.

Adult↗
PubMed1998

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow.

The purpose of this study was to examine the bioenergetics and regulation of O2 uptake (VO2) and force production in contracting muscle when blood flow was moderately reduced during a steady-state contractile period. Canine gastrocnemius muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic (I) condition] to 46 +/- 3% of the value obtained at 0.5 Hz with normal blood flow. The VO2 of the contracting muscle was significantly (P < 0.05) reduced during the I condition [6.5 +/- 0.8 (SE) ml . 100 g-1 . min-1] compared with the same stimulation frequency with normal flow (11.2 +/- 1.5 ml . 100 g-1 . min-1), as was the tension-time index (79 +/- 12 vs. 123 +/- 22 N . g-1 . min-1, respectively). The ratio of VO2 to tension-time index remained constant throughout all contraction periods. Muscle phosphocreatine concentration, ATP concentration, and lactate efflux were not significantly different during the I condition compared with the 0. 5-Hz condition with normal blood flow. However, at comparable rates of VO2 and tension-time index, muscle phosphocreatine concentration and ATP concentration were significantly less during the I condition compared with normal-flow conditions. These results demonstrate that, in this highly oxidative muscle, the normal balance of O2 supply to force output was maintained during moderate ischemia by downregulation of force production. In addition, 1) the minimal disruption in intracellular homeostasis after the initiation of ischemia was likely a result of steady-state metabolic conditions having already been activated, and 2) the difference in intracellular conditions at comparable rates of VO2 and tension-time index between the normal flow and I condition may have been due to altered intracellular O2 tension.

Adenosine Triphosphate↗
PubMed1998

Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in situ canine muscle.

The mechanism(s) limiting muscle O2 uptake (VO2) kinetics was investigated in isolated canine gastrocnemius muscles (n = 7) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peak V(O2)). Two conditions were mainly compared: 1) spontaneous adjustment of blood flow (Q) [control, spontaneous Q (C Spont)]; and 2) pump-perfused Q, adjusted approximately 15 s before contractions at a constant level corresponding to the steady-state value during contractions in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2 Delivery, 1-2 ml/min of 10(-2) M adenosine were infused intra-arterially to prevent inordinate pressure increases with the elevated Q. The purpose of the study was to determine whether a faster adjustment of O2 delivery would affect V(O2) kinetics. Q was measured continuously; arterial (Ca(O2)) and popliteal venous (Cv(O2)) O2 contents were determined at rest and at 5- to 7-s intervals during contractions; O2 delivery was calculated as Q x Ca(O2), and V(O2) was calculated as Q x arteriovenous O2 content difference. Times to reach 63% of the difference between baseline and steady-state VO2 during contractions were 23.8 +/- 2.0 (SE) s in C Spont and 21.8 +/- 0.9 s in Fast O2 Delivery (not significant). In the present experimental model, elimination of any delay in O2 delivery during the rest-to-contraction transition did not affect muscle V(O2) kinetics, which suggests that this kinetics was mainly set by an intrinsic inertia of oxidative metabolism.

Animals↗