Biomedical subjects

P Pasqualetti

Publications and source records attributed to P Pasqualetti.

At least 55 records · Page 3Linked to original sources

PubMed2000

Intracortical excitatory and inhibitory phenomena to paired transcranial magnetic stimulation in healthy human subjects: differences between the right and left hemisphere.

Intracortical inhibition (ICI) and facilitation (ICF) to paired magnetic stimuli reflect the activation of interneuronal circuits within the motor cortex. Intersubjects physiological variability of these phenomena, partly limits the usefulness of such method. Therefore, interhemispheric ICI/ICF differences might represent a more sensitive and less variable neurophysiological parameter to test the motor cortex excitability. Motor evoked potentials from the hand muscles were recorded in ten healthy subjects in a paired-pulse paradigm. Interstimulus intervals (ISIs) from 1 to 50 ms were used. The time course of ICI and ICF in the two hemispheres is consistent with minimal interhemispheric asymmetries. The interhemispheric differences of ICI and ICF could be a valuable neurophysiological marker for the diagnosis, prognosis and follow-up of neurological diseases characterized by monohemispheric damage and lateralized motor deficits.

Cerebral Cortex↗

PubMed2000

Morphology of somatosensory evoked fields: inter-hemispheric similarity as a parameter for physiological and pathological neural connectivity.

The morphology of somatosensory evoked fields (SEF) following electrical separate stimulation of left and right median nerve in 22 healthy volunteers was explored. The analysis of morphological properties of individual SEFs has been performed, in order to quantify an inter-hemispheric correlation coefficient. Despite a high inter-subject variability of the SEF morphologies, a high intra-subject inter-hemispheric shape correlation occurs in the post-stimulus epoch of 100 ms from the stimulus onset. Accordingly, a normative value for the parameter describing the SEF inter-hemispheric correlation coefficient has been calculated. The present work establishes quantitative and normative descriptions of the shape similarity of SEFs from the two hands in the left and right hemispheres. This provides a database for a new parameter, which might be useful in detecting alterations in the primary sensory cortical activation due to possible unilateral alterations of sensory inflow because of either peripheral or central deficits. The described procedure has been successfully applied to a small number of patients affected by unilateral cerebrovascular lesion.

Adult↗

PubMed2000

Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis.

CONTEXT: Standards for treating patients with asymptomatic carotid artery stenosis have been difficult to establish because of the lack of evidence for factors influencing these patients' prognoses. However, preliminary evidence suggests that an alteration in cerebral hemodynamic function may play a relevant role in the occurrence of stroke in patients with carotid artery disease. OBJECTIVE: To investigate the relationship between cerebrovascular reactivity to hypercapnia and cerebrovascular events in patients with severe unilateral asymptomatic carotid artery stenosis. DESIGN AND SETTING: Prospective, blinded longitudinal study conducted in an outpatient neurovascular department in Italy between June 1996 and April 1998, with a median follow-up of 28.5 months. PATIENTS: Ninety-four patients with asymptomatic carotid artery stenosis of at least 70% (74 men; mean age, 71 years). MAIN OUTCOME MEASURES: Subsequent occurrence of cerebral ischemic events (transient ischemic attack or stroke) or death, analyzed by cerebrovascular reactivity to hypercapnia (measured by transcranial Doppler ultrasonography and calculated by the breath-holding index values in the middle cerebral arteries). RESULTS: The overall annual rate for all ischemic events was 7.9%. Seventeen patients (18%) had ischemic events, all but 1 of which were ipsilateral to the carotid artery stenosis. Among factors considered, only lower breath-holding index values in the middle cerebral artery ipsilateral to carotid artery stenosis were significantly associated with the risk of an event (hazard ratio, 0.09; 95% confidence interval, 0.02-0.38; P=.001, by multivariate analysis). Based on data from previously studied healthy subjects, the cutoff of the breath-holding index for distinguishing between impaired and normal cerebrovascular reactivity was determined to be 0.69. Using this cutoff, the annual ipsilateral ischemic event risk was 4.1% in patients with normal and 13.9% in those with impaired breath-holding index values. CONCLUSIONS: These results suggest a link between impaired cerebrovascular reactivity and the risk of ischemic events ipsilateral to severe asymptomatic carotid stenosis.

Aged↗

PubMed2000

Transcranial magnetic stimulation reveals an interhemispheric asymmetry of cortical inhibition in focal epilepsy.

Transcranial magnetic stimulation (TCS) was applied to both hemispheres of 16 patients affected by criptogenic focal epilepsy to evaluate the interhemispheric symmetry of the motor cortex excitability. The amplitude of the motor evoked potentials (MEPs) and the duration of the post-MEP silent period (SP) were measured at threshold (THR) and at increasing TCS stimulation intensities. The THR was significantly higher in patients than in 16 age-matched control subjects (p < 0.01). No interhemispheric differences were found in MEP amplitude. In controls, the correlation between SP duration and increasing TCS stimulus intensity was linear with a symmetrical progression of the SP duration over the two hemispheres. In patients this linear SP progression was lacking on the 'epileptic' hemisphere: the SP duration did not increase following TCS > 40% above THR, indicating abnormal interhemispheric asymmetry. This finding suggests a selective dysfunction of inhibition in the epileptic hemisphere as signaled by an abnormal SP duration in response to progressively higher TCS intensities.

Adolescent↗

PubMed2000

Flow cytometric DNA ploidy, p53, PCNA, and c-erbB-2 protein expressions as predictors of survival in surgically resected gastric cancer patients.

In order to determine retrospectively the impact of some cytometric and immunohistochemical parameters on the overall survival of gastric cancer patients treated with surgery alone, paraffin-embedded tumor samples from 137 gastric carcinoma patients undergoing curative resection from 1987-1993 were analyzed by flow cytometry (FCM) and immunohistochemistry (p53, c-erbB-2, and PCNA expression). FCM-derived parameters were DNA ploidy and fraction of S-phase cells (SPF). Multiple regression analysis was applied to determine the prognostic significance of the conventional clinicopathologic findings together with the flow cytometric and immunohistochemical parameters on overall survival. When all parameters were entered simultaneously into the Cox regression model, stage and DNA ploidy (DNA index >1.35) clearly emerged as the only independent prognostic factors. When the stages were analysed separately, the independent prognostic factors resulted DNA ploidy in early stages (I-II) and grading in stage IIIA tumors. For stage IIIB tumors, no independent prognostic factor was found. These results indicate that the DNA ploidy pattern is a valuable predictor of survival in curatively resected gastric cancer patients, especially when less advanced tumors are taken into consideration.

Adult↗

PubMed2000

Tonotopic cortical changes following stapes substitution in otosclerotic patients: a magnetoencephalographic study.

The aim of the study was to investigate and follow up the tonotopic organization of the primary auditory cortex in otosclerotic patients before and after corrective surgery. The characteristics of primary auditory cortex activation were studied in ten otosclerotic patients (i.e., subjects suffering from a conductive hearing loss, prior to and following stapes substitution). Magnetoencephalographic recordings of auditory evoked fields by tone-burst stimulation at octave frequencies between 250 and 2000 Hz were performed during monaural stimulation. The brain topography of the main cortical response (N100m) generators at different tones was studied in patients and compared with ten healthy controls; pre- post-surgical changes were also correlated to their clinical outcome following corrective surgery. A significant decrease of the tonotopic extension in the cortical region responsive to the four explored frequencies was found in patients before surgery with respect to the control population. At the time of postsurgical follow-up, the tonotopic representation had enlarged and was approaching the dimensions seen in normal subjects, although with higher variability. The extent of the enlargement of the postoperative tonotopically organized area was directly correlated with the postsurgery period duration. Our findings indicate that auditory cortical areas of human adults undergo functional reorganization following peripheral alteration of the sensory input entering the CNS. The restriction of the cortical tonotopic region caused by the long-term reduction of acoustic input is followed by a reorganization within the usual boundaries following the recovery of auditory function; this process is taking place in a time scale of a few weeks.

Adult↗

PubMed2000

Conscious and preconscious adaptation to rhythmic auditory stimuli: a magnetoencephalographic study of human brain responses.

This study was triggered by the experimental evidence that subjects required to tap in synchrony with a heard rhythm spontaneously time their tapping to variations in rhythm frequency even when these variations are so small that they are not consciously detectable. We performed a series of magnetoencephalographic (MEG) measurements, aimed at investigating whether the response of the auditory cortex discriminates randomly administered series of brief tones differing from each other only by their interstimulus intervals (ISI). Moreover, by combining psychophysical measurements, conscious and preconscious adjustments of tapping to rhythm variations were compared with brain cortical responses. The ISIs were varied by 2% or 20% from a "central" value of 500 ms. Subjects always consciously detected the 20% ISI changes and easily adjusted their tapping accordingly, whereas they never consciously detected the 2% ISI changes, even though they always correctly adjusted their tapping to them. Analysis of the auditory evoked fields (AEFs) showed that the intensity of the M100 component decreased with decreasing ISI both for 20% and 2% variations in a statistically significant manner, despite the fact that the 2% variation was not consciously perceived. The M100 behavior indicated that connections between auditory and motor cortexes may exist that are able to use the information on rhythm variations in the stimuli even when these are not consciously identified by the subject. The ability of the auditory cortex to discriminate different time characteristics of the incoming rhythmic stimuli is discussed in this paper in relation to the theories regarding the physiology of time perception and discrimination.

Acoustic Stimulation↗

PubMed2000

Effects of microwaves (900 MHz) on the cochlear receptor: exposure systems and preliminary results.

The purpose of this paper is to present the experimental device and the work in progress performed in search for objective organic correlation of damage to hearing, examining possible acoustic otofunctional effects on the cochlear epithelium of the rat due to exposure to microwaves (900 MHz). Two experiments using male Sprague-Dawley rats were carried out with a far-field exposure in a cubic chamber. No statistically significant evidence was obtained at both specific absorption rate (SAR) values. The exposure system and the diagnostic apparatus are extremely useful to investigate a potential effect on the auditory system: however, with the parameters applied in these experiments, no evidence was observed.

Animals↗

PubMed2000

Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup.

OBJECTIVE: This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred and ninety-five patients with VKC. METHODS: Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. MAIN OUTCOME MEASURES: (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. RESULTS: VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. CONCLUSIONS: VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex-related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Adolescent↗

PubMed2000

Neurophysiological evaluation of tactile space perception deficits through transcranial magnetic stimulation.

We describe a procedure useful to investigate the contralateral space perception deficits frequently encountered in patients with unilateral right brain damage. In particular, we focused on the phenomenon of extinction, i.e., the failure to perceive a contralesional stimulus only when a symmetrical contralateral stimulus is simultaneously applied. Fifteen right brain- and 15 left brain-damaged patients were examined. Somatosensory perception was evaluated by using a dedicated electronic device able to provide electrical stimuli of variable intensity to digits of one or both hands. The electrical stimulator was able to trigger a magnetic brain stimulator connected with a focal figure of eight coil. Threshold electrical stimuli were delivered to one or both hands of the patients, who were asked to indicate whether they perceived the stimulus (i) and to localise it (them). The electrical stimulator was connected with a magnetic stimulator with an interstimulus interval (ISI) of 40 msec (electrical stimulation preceding the transcranial one). Focal threshold transcranial magnetic stimulation (TMS) was applied to frontal and parietal scalp sites of the unaffected hemisphere. At each interpulse interval we found that TMS of the unaffected hemisphere was associated to a decrease in the level of contralesional extinction. Our method demonstrates that a basic deficit underlying neglect and extinction of contralateral space in unilaterally brain damaged patients is the interhemispheric imbalance between the two hemispheres in directing contralateral attention. A transient interference with the function of the unaffected hemisphere can improve these deficits, suggesting a possible application of TMS in the daily clinical practice for speeding up recovery from neglect.

Cognition↗

PubMed2000

Neurophysiological follow-up of motor cortical output in stroke patients.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been employed in following up a population of 20 stroke patients in a post-acute, apparently stabilized stage. Neurophysiological and clinical data were recorded in 5 different recording sessions, from the beginning of a neuro-rehabilitation treatment (T0, at about 5 weeks from the ictal event.), followed up for about 4 months (T4), with the purpose to study any modification of the cortical motor output in the course of a neuro-rehabilitation treatment. METHODS: Motor evoked potentials (MEPs) were simultaneously recorded from 10 muscles of both upper limbs (affected and not-affected); meanwhile, clinical and functional scores were gathered. Spinal responsiveness was investigated via H-reflex and F-wave recordings. RESULTS: We describe a pattern of improving changes still taking place four months after the stroke, even if the maximal amelioration burden was concentrated between T0 and T1 and T1 and T2 recording sessions (T0/admission to T2/42 days from T0=about 80 days from stroke occurrence). In particular, the excitability threshold (ETh) was progressively decreasing in the affected hemisphere (AH; P<0.001 between T0 and T4), while MEPs amplitude and latency tended toward normality, more in the resting state than during voluntary contraction. Slopes of neurophysiological and clinical data evolution were taken and trends of amelioration described. CONCLUSIONS: These findings suggest that rearrangements of motor cortical neural circuitries are still operating after several months from an acute vascular monohemispheric insult, coupled with a clinical improvement in disability and neurological scores. The steepest part of the slopes were evident in the first 80 days, suggesting that this period is the one in which plastic changes of cortical motor areas are mainly active.

Female↗

PubMed2000

Time-dependent activation of parieto-frontal networks for directing attention to tactile space. A study with paired transcranial magnetic stimulation pulses in right-brain-damaged patients with extinction.

Tactile extinction has been interpreted as an attentional disorder, closely related to hemineglect, due to hyperactivation of the unaffected hemisphere, resulting in an ipsilesional attentional bias. Paired transcranial magnetic stimulation (TMS) techniques, with a subthreshold conditioning stimulus (CS) followed at various interstimulus intervals (ISIs) by a suprathreshold test stimulus (TS), are useful for investigating intracortical inhibition and facilitation in the human motor cortex. In the present work, we investigated the effects of paired TMS over the posterior parietal and frontal cortex of the unaffected hemisphere in a group of eight right-brain-damaged patients with tactile extinction who were carrying out a bimanual tactile discrimination task. The aim of the study was to verify if paired TMS could induce selective inhibition or facilitation of the unaffected hemisphere depending on the ISI, resulting, respectively, in an improvement and a worsening of contralesional extinction. In addition, we wanted to investigate if the effects of parietal and frontal TMS on contralesional extinction appeared at different intervals, suggesting time-dependent activation in the cortical network for the processing of tactile spatial information. Paired TMS stimuli with a CS and a TS, separated by two ISIs of 1 and 10 ms, were applied over the left parietal and frontal cortex after various intervals from the presentation of bimanual cutaneous stimuli. Single-test parietal TMS stimuli improved the patients' performance, whereas paired TMS had distinct effects depending on the ISI: at ISI = 1 ms the improvement in extinction was greater than that induced by single-pulse TMS; at ISI = 10 ms we observed worsening of extinction, with complete reversal of the effects of single-pulse TMS. Compared with TMS delivered over the frontal cortex, parietal TMS improved the extinction rate in a time window that began earlier. These findings shed further light on the mechanism of tactile extinction, suggesting relative hyperexcitability of the parieto-frontal network in the unaffected hemisphere, which is amenable to study and modulation by paired TMS pulses. In addition, the results show time-dependent processing of tactile spatial information in the parietal and frontal cortices, with a bimodal distribution of activity, at least in the attentional network of the unaffected hemisphere.

Aged↗

PubMed2000

Effects of repetitive transcranial magnetic stimulation on movement-related cortical activity in humans.

Several lines of evidence suggest that low-rate repetitive transcranial magnetic stimulation (rTMS) of the motor cortex at 1 Hz reduces the excitability of the motor cortex and produces metabolic changes under and at a distance from the stimulated side. Therefore, it has been suggested that rTMS may have beneficial effects on motor performance in patients with movement disorders. However, it is still unknown in what way these effects can be produced. The aim of the present study is to investigate whether rTMS of the motor cortex (15 min at 1 Hz) is able to modify the voluntary movement related cortical activity, as reflected in the Beretischaftspotential (BP), and if these changes are functionally relevant for the final motor performance. The cortical movement-related activity in a typical BP paradigm of five healthy volunteers has been recorded using 61 scalp electrodes, while subjects performed self-paced right thumb oppositions every 8-20 s. After a basal recording, the BP was recorded in three different conditions, counterbalanced across subjects: after rTMS stimulation of the left primary motor area (M1) (15 min, 1 Hz, 10% above motor threshold), after 15 min of sham rTMS stimulation and following 15 min of voluntary movements performed with spatio-temporal characteristics similar to those induced by TMS. The tapping test was used to assess motor performance before and after each condition. Only movement-related trials with similar electromyographic (onset from muscular 'silence') and accelerometric patterns (same initial direction and similar amplitudes) were selected for computing BP waveforms. TMS- evoked and self-paced thumb movements had the same directional accelerometric pattern but different amplitudes. In all subjects, the real rTMS, but neither sham stimulation nor prolonged voluntary movements, produced a significant amplitude decrement of the negative slope of the BP; there was also a shortening of the BP onset time in four subjects. The effect was topographically restricted to cortical areas which were active in the basal condition, irrespective of the basal degree of activation at every single electrode. No changes in the tapping test occurred. These findings suggest that rTMS of the motor cortex at 1 Hz may interfere with the movement related brain activity, probably through influence on cortical inhibitory networks.

Adult↗

PubMed2000

Recognition of facial expressions of emotions in school-age children: the intersection of perceptual and semantic categories.

UNLABELLED: Recognition of the facial expressions of emotions is a critical communicative system early in development and continues to play an important role throughout adulthood. In the past, the results of developmental studies of emotional facial recognition have often conflicted. The present study was designed to examine the development of emotional facial recognition in a large sample of school-aged children (n = 120, ages 5-10y). In particular, we investigate whether emotion categories, i.e., those based on the visual spatial parameters of facial expression, develop in a similar fashion to those that also recruit lexical knowledge of emotion terms. We have found two distinct patterns of development and we suggest that these different profiles are a consequence of the very different cognitive abilities that they recruit. CONCLUSION: Emotion cognition is a variegated domain which is differentially related to such areas of cognition as visuo-spatial and lexical semantic abilities.

Age Distribution↗

PubMed1999

Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty.

OBJECTIVES: We sought to investigate whether early and late outcome after percutaneous transluminal coronary angioplasty (PTCA) could be predicted by baseline levels of acute-phase reactants. BACKGROUND: Although some risk factors for acute complications and restenosis have been identified, an accurate preprocedural risk stratification of patients undergoing PTCA is still lacking. METHODS: Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and fibrinogen were measured in 52 stable angina and 69 unstable angina patients undergoing single vessel PTCA. RESULTS: Tertiles of CRP levels (relative risk [RR] = 12.2, p < 0.001), systemic hypertension (RR = 4.3, p = 0.046) and female gender (RR = 4.1, p = 0.033) were the only independent predictors of early adverse events. Intraprocedural and in-hospital complications were observed in 22% of 69 patients with high serum levels (>0.3 mg/dl) of CRP and in none of 52 patients with normal CRP levels (p < 0.001). Tertiles of CRP levels (RR = 6.2, p = 0.001), SAA levels (RR = 6.0, p = 0.011), residual stenosis (RR = 3.2, p = 0.007) and acute gain (RR = 0.3, p = 0.01) were the only independent predictors of clinical restenosis. At one-year follow-up, clinical restenosis developed in 63% of patients with high CRP levels and in 27% of those with normal CRP levels (p < 0.001). CONCLUSIONS: Preprocedural CRP level, an easily measurable marker of acute phase response, is a powerful predictor of both early and late outcome in patients undergoing single vessel PTCA, suggesting that early complications and clinical restenosis are markedly influenced by the preprocedural degree of inflammatory cell activation.

Aged↗

PubMed1999

Time course of frontal somatosensory evoked potentials. Relation to L-dopa plasma levels and motor performance in PD.

OBJECTIVE: To verify whether the change in L-dopa plasma levels after a single dose of carbidopa/L-dopa 50/200 (controlled-release) transiently modifies frontal components of somatosensory evoked potentials (SEPs) in patients with PD in parallel with improvement of motor performance. BACKGROUND: Apomorphine, a potent dopamine-agonist drug, transiently increases frontal SEP components, which may be depressed in PD; however, relationships between clinical status, frontal SEPs, and therapy are still unclear. METHODS: Nineteen PD patients (mean age 65.9 years, range 52 to 77, responders to L-dopa therapy, were studied in the same day at times T0 (baseline predose level), T1 (presumed L-dopa peak time), and T2 (end of dose-induced motor response). The following were monitored: L-dopa plasma concentration, tapping test, reaction times, peak latency (with central conduction times), and amplitude of cervical, subcortical, as well as cortical parietal and frontal SEP components elicited by median nerve stimulation of the more clinically affected arm. RESULTS: The average amplitude of frontal components of PD patients was significantly reduced at T0 with respect to control subjects. A significant and transient amplitude increase of frontal SEPs was found at T1, in parallel with the L-dopa peak concentration and improvement in motor performance (tapping and reaction times), without significant changes in amplitude of parietal SEP waves. No latency shifts were observed in brain and spinal waves. CONCLUSIONS: L-Dopa may influence the responsiveness of the parkinsonian brain as assessed by frontal somatosensory evoked potentials. The time course of these modifications coincides with that of the clinical response in the motor performance.

Aged↗

PubMed1999

Effect of paired transcranial magnetic stimulation on the cortical silent period.

OBJECTIVE: To investigate the behaviour of silent period (SP) during paired magnetic cortical stimulation. BACKGROUND: Paired cortical magnetic stimulation is known to inhibit or facilitate motor evoked potentials (MEPs), but no attention has been paid to its effect on SP. METHODS: SP was measured in the contracted first dorsal interosseus muscle after paired cortical stimuli at given interstimulus intervals (ISIs) in eight healthy subjects. Test stimulus intensity was fixed at 110% of resting threshold (RT), while three levels of conditioning stimulus intensities at 40%, 65% and 90% RT were separately employed. We also examined the effect of progressively increasing the test stimulus intensity (120-150 RT) on SP while maintaining stable conditioning stimulus intensity. RESULTS: 65% RT conditioning stimulus shortened the SP at 1-3 ms ISIs with MEP size reduction, and prolonged the SP at 15-20 ms ISIs without affecting MEP size. 90% RT conditioning stimulus showed only SP prolongation, while 40% RT showed only SP shortening at 1 ms ISI. The SP shortening at 2 ms ISI was the most evident with 120% RT test stimulus, but without correlation with the MEP size. The SP prolongation at 15 ms ISI was maximal with 110% RT test stimulus and then almost abolished with 150% RT. The SP shortening at short intervals might be due not only to spinal but also to suprasegmental mechanisms, conceivably mediating cortical excitatory drive to the corticospinal tract. The SP prolongation at intermediate intervals might be due to activation of slowly conducting, intra- or sub-cortical polysynaptic pathways exerting a facilitatory drive on the cortical inhibitory interneurons.

Adult↗

PubMed1999

Hyperthermia enhances the response of paclitaxel and radiation in a mouse adenocarcinoma.

PURPOSE: The aim of our study was to investigate if the efficacy of paclitaxel and paclitaxel-radiation treatments in vivo could be enhanced by hyperthermia. MATERIALS AND METHODS: Paclitaxel was administered i.p. in doses from 30 to 60 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Local hyperthermia (41 degrees, 42 degrees, 43 degrees C) was carried out by immersing tumor-bearing legs in a water bath for 1 h. Single X-ray treatments from 10 to 90 Gy were performed. Tumor growth delay (TGD) or tumor control dose (TCD(50), radiation dose needed to induce local tumor control in 50% of irradiated animals) were the endpoints. RESULTS: A significant increase of dose-dependent growth delay was observed in paclitaxel and 43 degrees C hyperthermia combined treatments, and a superadditive effect was seen with paclitaxel 45 mg/kg. Combined treatments with hyperthermia at 41 degrees and 42 degrees C were less effective. Administration of paclitaxel 24 h, 4 h, and 15 min before or 15 min and 4 h after hyperthermic treatments produced similar results (TGDs varying from 22.1 to 17 days), and administering paclitaxel 48 h before or 24 h after hyperthermic treatments decreased TGDs (about 10 days). Trimodality treatment (paclitaxel 45 mg/kg, hyperthermia, and X-ray), with a TCD(50) of 14. 1 Gy, in respect to the TCD(50) of 53.1 obtained with X-ray alone, was the most effective. CONCLUSIONS: Hyperthermia enhanced the effectiveness of paclitaxel in all the tested protocols. Our results show a superadditive effect of paclitaxel 45 mg/kg combined with a hyperthermic treatment of 1 h at 43 degrees C. Trimodality treatment, evaluated in terms of percentage of cures, shows a very high enhancement ratio.

Analysis of Variance↗