Search PubMed⌕ Search

Biomedical subjects

H Johansson

Publications and source records attributed to H Johansson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Correlation between tamoxifen elimination and biomarker recovery in a primary prevention trial.

We have shown previously that a reduction from the conventional dose of tamoxifen is associated with a comparable modulation of circulating biomarkers, including insulin-like growth factor-I and cholesterol. In the present study, we have correlated serum tamoxifen elimination with biomarker recovery in healthy subjects completing a 5-year intervention period. Tamoxifen, N-desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and 6 weeks after completion of treatment in 23 healthy postmenopausal women allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (+/-SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively, 141 +/- 50 and 226 +/- 77 ng/ml at baseline, 36 +/- 19 and 99 +/- 46 at 2 weeks, 20 +/- 15 and 61 +/- 37 at 4 weeks, and 12 +/- 9 and 36 +/- 26 at 6 weeks. Serum tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively. Body mass index was associated positively with drug's serum half-life. Compared with baseline values, the percentage increase in total cholesterol, low-density lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment completion was 5, 9, and 14%, respectively. No change during the 6-week period was observed in the placebo arm. Our findings indicate that the biomarker recovery is slower than serum tamoxifen elimination, suggesting that low tamoxifen concentrations may still exert a biological effect. In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined.

Aged↗
PubMed2001

Long-term effects of fenretinide, a retinoic acid derivative, on the insulin-like growth factor system in women with early breast cancer.

High insulin-like growth factor-I (IGF-I) levels are associated with an increased risk of breast cancer in premenopausal women. Because the synthetic retinoid fenretinide showed a beneficial effect on second breast cancers in premenopausal women in a Phase III trial, we studied its long-term effects on IGF-I levels. We measured, at yearly intervals for up to 5 years, the circulating levels of IGF-I, IGF binding protein (BP)-3, and their molar ratio in 60 subjects < or = 50 years of age and 60 subjects > 50 years of age allocated either to fenretinide or no treatment. In women < or = 50 years of age, measurements of IGF-II, IGFBP-1, and IGFBP-2 were also performed. The associations between biomarkers and drug or metabolite plasma concentrations were also investigated. All biomarkers were relatively stable over 5 years in the control group. Compared with controls and after adjustment for baseline, treatment with fenretinide for 1 year induced the following changes: IGF-I, -13% [95% confidence interval (CI), -25 to 1%] in women < or = 50 years of age and -3% (95% CI, -16 to 13%) in women > 50 years of age; IGFBP-3, -4% (95% CI, -12 to 6%) in both age groups; IGF-I:IGFBP-3 molar ratio, -11% (95% CI, -22 to 1%) in women < or = 50 years of age and 1% (95% CI, -11 to 16%) in women > 50 years of age. These effects were apparently maintained for up to 5 years, although fewer samples were available as time progressed. No change in other IGF components was observed. Drug and metabolite concentrations were negatively correlated with IGF-I and IGF-I:IGFBP-3 molar ratio in women < or = 50 years of age. Fenretinide induces a moderate decline of IGF-I levels in women < or = 50 years of age. The association between IGF-I change and the reduction of second breast cancers in premenopausal women warrants further study.

Adult↗
PubMed2001

Information theoretic analysis of muscle spindles.

The information transmission properties of single, deefferented, primary muscle spindle afferents (MSAs) from the hind limb of the cat were investigated. Random stretches were delivered to the gastrocnemius medialis muscle, while recording spike trains from several MSAs near the dorsal root. Two classes of input stimuli were used: Gaussian noise with band-limited flat spectrum, and Gaussian noise with a more "naturalistic" 1/fn spectrum. The "reconstruction" method was used to calculate a lower bound to the information rate (in bit/ sec) delivered from MSAs to the spinal cord. Results show that in response to flat spectrum primary MSAs transfer information mainly about high frequencies, carrying 1.97 bits per spike. In response to naturalistic spectrum MSAs transfer information about both low and high frequencies, with "spiking efficiency" increasing to 2.99 bits per spike. A simple muscle spindle model was simulated, exemplifying the part of the intrafusal fiber mechanical properties in information transmission.

Animals↗
PubMed2000

Long term results of a randomized study by the Swedish Melanoma Study Group on 2-cm versus 5-cm resection margins for patients with cutaneous melanoma with a tumor thickness of 0.8-2.0 mm.

BACKGROUND: Large, prospective, randomized trials with long term follow-up are required to obtain an unbiased evaluation of the significance of resection margins in patients with cutaneous melanoma. METHODS: The Swedish Melanoma Study Group performed a prospective, randomized, multicenter study of patients with primary melanoma located on trunk or extremities and with a tumor thickness > 0.8 mm and </= 2 mm. Patients were allocated randomly to a 2-cm excision margin or a 5-cm excision margin. In total, 989 patients were recruited during the period 1982-1991. The median follow-up was 11 years (range, 7-17 years) for estimation of survival and 8 years (range, 0-17 years) for evaluation of recurrent disease. RESULTS: The crude rate of local recurrence, defined as a recurrence in the scar or transplant, was < 1% (8 of 989 patients). Twenty percent of the patients (194 of 989 patients) experienced any disease recurrence, and 15% (146 of 989 patients) died of melanoma. There were no statistically significant differences between the two treatment arms. In a multivariate Cox analysis with patients allocated to wide excision as the reference group, the estimated relative hazards for overall survival and recurrence free survival among those allocated to a 2-cm resection margin were 0.96 (95% confidence interval, 0.75-1.24), and 1.02 (95% confidence interval, 0.80-1.30), respectively. CONCLUSIONS: In this long term follow-up study, local recurrences were found to be rare among patients with tumors > 0.8 mm thick and </= 2.0 mm thick. No difference in recurrence rate or survival between the two treatment groups was found. Patients in this category can be treated with a resection margin of 2 cm as safely as with a resection margin of 5 cm.

Adolescent↗
PubMed2000

[Improved therapeutic results in rectal cancer. Preoperative radiotherapy and continuing education of the surgeons is efficient].

The aim of the Stockholm Colorectal Cancer Study Group is to improve treatment results in colorectal cancer. Between 1980 and 1993 the group conducted two randomised trials on preoperative radiotherapy in rectal cancer including 1406 patients. In both trials radiotherapy significantly reduced local recurrence and improved cancer specific survival. To further improve treatment results, four workshops have been held to introduce the "TME concept" to surgeons in Stockholm. The workshops included live surgical demonstrations and histopathology sessions. When patients included in the Stockholm trials (1980-1993) were compared to patients included in the "TME project" (1995-1996) the rate of abdominoperineal procedures was reduced from 60 to 27 per cent. Within two years of follow up the local recurrence rate was reduced from 15 to 6 per cent and cancer related deaths from 16 to 9 per cent. It is concluded that surgical teaching initiatives may have a significant impact on cancer outcomes.

Clinical Competence↗
PubMed2000

Time course of fenretinide-induced modulation of circulating insulin-like growth factor (IGF)-i, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial.

The insulin-like growth factor (IGF) system is widely involved in human carcinogenesis. A significant association between high circulating IGF-I concentrations and an increased risk of lung, colon, prostate and pre-menopausal breast cancer has recently been reported. Lowering plasma IGF-I may thus represent an attractive strategy to be pursued for chemopreventive purposes. We have previously shown that the synthetic retinoid fenretinide (4-HPR) lowers plasma IGF-I in pre-menopausal breast cancer patients. We investigated the effect of fenretinide on circulating IGF-I, IGF-II and IGFBP-3 measured at yearly intervals during the 2-year treatment period and one year after treatment discontinuation in a predominantly male population of patients with superficial bladder cancer. Repeated measures analysis, after adjustment for age, body mass index (BMI) and year of study, showed a significant effect of fenretinide on IGF-I levels, which were further lowered after the second year of treatment and only partially recovered after drug discontinuation. Differently from breast cancer patients, the effect of fenretinide was not modified by age. No significant effect was evident on IGFBP-3, IGF-II and the IGF-I+IGF-II/IGFBP-3 molar ratio, expressing the tissue availability of the mitogenic peptides, although IGF-II and the molar ratio were lowered by treatment by an overall mean of 16% and 15%, respectively. Given the increasingly recognized importance of circulating IGFs in the pathogenesis of different solid tumors, our findings strengthen the rationale for studying fenretinide as a chemopreventive agent.

Age Factors↗
PubMed2000

Trends in mortality from malignant melanoma in Sweden, 1970-1996.

BACKGROUND: The rise in melanoma-related mortality in Sweden has been less pronounced than the increase in incidence. Interventional activities aimed at early detection may have contributed to this discrepancy. METHODS: Individuals with malignant melanoma as the underlying cause of death between 1970 and 1996 (n = 7177) formed the basis of this study. Annual age-standardized mortality rates were calculated using the direct method of standardization with the Swedish population of 1970 as reference. Temporal trends in the standardized rates were evaluated using a log-linear model. The effects of age, period, and cohort on the mortality trends were estimated using a Poisson regression model. RESULTS: Since the mid-1980s, melanoma-related mortality in Sweden has leveled off, with no further increase during the last 10-15 years. The contribution to the mortality from noncutaneous melanoma was proportionally stable (20-25%) during the studied period. In females, a significant decrease in mortality from cutaneous melanoma was shown for the period of 1987-1996 with an estimated annual decrease of -2.3% (95% confidence interval: -4.3 to -0.3). This trend appeared to be more pronounced in the Stockholm-Gotland region. The observed trends were best explained with the age-period model in both genders. CONCLUSIONS: Melanoma-related mortality in Sweden has leveled off since the mid-1980s. During the period 1987-1996, a statistically significant downward trend was observed for females. This trend coincides with increased preventional activities.

Adult↗
PubMed2000

Evidence that N-terminal fragments of nociceptin modulate nociceptin-induced scratching, biting and licking in mice.

The intrathecal (i.t.) injection of 3.0 fmol nociceptin (orphanin FQ) elicited scratching, biting and licking responses in mice. N-terminal fragments of nociceptin, nociceptin (1-7), nociceptin (1-9) and nociceptin (1-13), induced no characteristic behavioral response. When these N-terminal fragments of nociceptin were injected simultaneously with nociceptin, the behavioral response induced by nociceptin was reduced dose-dependently. Nociceptin (1-13) was much more potent than nociceptin (1-7) and nociceptin (1-9) and antagonized nociceptin-induced response at equimolar doses. No significant effects of the N-terminal fragments were observed against the scratching, biting and licking response elicited by i.t. administration of substance P or N-methyl-D-aspartate. These results suggest that N-terminal fragments formed endogenously in the spinal cord may have an antagonistic effect on nociceptin-induced behavioral responses.

Animals↗
PubMed2000

Position sense acuity is diminished following repetitive low-intensity work to fatigue in a simulated occupational setting.

Repetitive work to fatigue is soundly associated with work-related musculoskeletal disorders (WMSD), although the underlying mechanisms are poorly understood. In the present study, we tested the hypothesis that fatiguing work leads to proprioceptive deficits, which can be an initiating factor for the occurrence of WMSD. Thus, the position sense of the shoulder was determined for 13 males and 13 females before and after performing repetitive low-intensity arm work to fatigue in a simulated occupational setting. From a starting position of 45 degrees to the sagittal plane, position sense tests consisted of subjects attempting to actively reproduce target positions of horizontal movements to 15 degrees and 30 degrees (shoulder adduction) and to 60 degrees and 75 degrees (shoulder abduction). An analysis of variance revealed that the absolute error was significantly increased following fatigue for the subjects as a group (P < 0.001). Furthermore, females had an overall higher error than males (P < 0.01). No difference in error was detected for the shorter movements versus the longer movements. However, the overall absolute error for adduction was significantly higher than for abduction (P < 0.001). The results of the present study support the hypothesis of diminished proprioceptive acuity following low-intensity work to fatigue. A reduction in position sense acuity could lead to impairment in motor control, which would further impact on position sense. Thus, a vicious cycle may be activated that might result in WMSD. The poorer position sense acuity observed for females may contribute to the explanation of why females demonstrate a higher incidence of WMSD than males.

Adult↗
PubMed2000

Position sense testing: influence of starting position and type of displacement.

OBJECTIVE: To assess the effect of starting position, target position, and various types of limb displacement on repositioning tests commonly used for clinical evaluation of rehabilitation. SETTING: Controlled laboratory environment. PARTICIPANTS: Sixteen healthy volunteer subjects. MAIN OUTCOME MEASURE: Absolute error, ie, the absolute difference between target and replicate positions. DESIGN: Each subject performed four testing procedures consisting of different types of limb displacement (active, passive, and passive during antagonist muscle contraction). For each procedure, horizontal movements were performed ipsilaterally about the right glenohumeral joint from one intermediate starting position (40 degrees ) and two extreme starting positions (0 degrees and 80 degrees ). Four fixed target positions (16 degrees , 32 degrees, 48 degrees , 64 degrees ) were presented for each starting position. The subjects were required to replicate target position after returning to the respective starting position. RESULTS: Lower repositioning errors occurred with active displacement procedures compared with passive, and with the intermediate starting position compared with the extreme. Target position, however, had no effect on repositioning errors. CONCLUSIONS: Starting position and type of displacement should be considered in interpretations and comparisons of data from clinical studies.

Adult↗
PubMed2000

Fatigue-related changes in electomyogram activity of the cat gastrocnemius during frequency-modulated efferent stimulation.

Changes in the compound muscle action potentials of cat gastrocnemius muscle were studied during low- and high-frequency fatigue. Fatiguing session consisted of 25-28 repetitions of the standard single fatigue tests (1.5min interval between the tests) that included the part of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions in the muscle. The rate of the continuous part was changed in accordance with symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases of 4s duration the rate changed linearly within a 2s interval. During fatigue relative changes in compound muscle action potential waves were usually smaller than changes in tension. Within the same fatigue procedure applied to a fresh muscle, the drop in tension was as much as 35% for high-rate stimulation and 59-71% for low-rate stimulation, whereas the decrease of the peak-to-peak compound muscle action potential waves amplitudes did not exceed 10-20%. Compound muscle action potential waves underwent the most pronounced depression during high-rate stimulation, the decrease proceeding during the following phase of low-rate stimulation. The tension changes during long-lasting activation were different for low- and high-frequency fatigue, with more pronounced depression during low-rate stimulation. As a rule, compound muscle action potential waves changes followed opposite patterns. Compound muscle action potential waves progressively split up, which was probably associated with a continuous slowing of the action potentials in the most fatigable motor units and the subsequent disappearance of the reactions at least in part of the motor units. Hysteresis effects in muscle contraction seem to be able, at least in part, to compensate for some of the depressive effects appearing during conduction of action potentials in muscle fibres. Changes in the compound muscle action potentials were studied during development of the muscle fatigue. These changes showed pronounced dependency on stimulation rate allowing differentiating effects of low- and high-frequency stimulation of the efferents supplying muscle under study. At the same time the fatigue-related changes in the action potentials were noticeably smaller than changes in tension, thus supporting existing concepts in the field arguing that fatigue effects are mainly connected with corresponding activity-dependent changes in muscle contraction machinery.

Action Potentials↗
PubMed2000

Fatigue effects in the cat gastrocnemius during frequency-modulated efferent stimulation.

Effects of low- and high-frequency fatigue were studied on muscle dynamics in isometric conditions of the cat gastrocnemius. Fatiguing sessions consisted of 25-28 repetitions of the standard tests that included an 18-s interval of continuous frequency-modulated stimulation preceded and followed by single stimuli evoking twitch contractions. The rate of the continuous part was changed in accordance with a symmetrical double-trapezoidal signal, including three successive phases of constant rate at 10, 40 and 10s(-1); between these phases, each lasting for 4s, the rate changed linearly within a 2-s interval. The following modes of muscle activation were applied: (i) stimulation of single filaments constituting approximately one-fifth to one-seventh of the total cross-section of the L(7) and S(1) ventral roots; (ii) the distributed stimulation of five similar filaments; and (iii) direct stimulation of muscle through bipolar wire electrodes. A relative drop in tension, the fatigue index, expressed as the ratio at the end of a fatigue session over its value at the beginning of the test, was used to quantify fatigue effects. The fatigue indices during low-rate stimulation were 0.56+/-0.03 (mean+/-S.D.) at the first phase and 0. 64+/-0.02 at the third phase, while during high-rate stimulation this parameter was only 0.32+/-0.02. The high-rate stimulation noticeably increased the mean tension during low-rate stimulation; the ratio between the reactions at the third and the first phases could be as much as two to three times greater than that at the beginning of the fatigue session. It was demonstrated that the potentiation was connected with after-effects of the rate-tension hysteresis. The hysteresis decreased with fatigue, the fatigue index for the rate-tension loop areas ranging from 0.39 to 0.52 (0.45+/-0. 05, mean+/-S.D.). The fatigue processes developed more quickly and intensively in the previously fatigued muscles: the obtained fatigue indices were 0.73+/-0.05 and 0.70+/-0.10 at the first and third phases, and 0.62+/-0.06 (mean+/-S.D.) at the second phase of stimulation, respectively. In the cases of distributed and direct stimulation applied to muscles in a fresh state, fatigue dynamics did not differ significantly from those observed during single-filament stimulation. In experiments with distributed stimulation applied to previously fatigued muscles, a powerful depression of the high-rate components was registered in several cases, which seemed to be connected with depressive effects at the level of nerve-muscle synaptic transmission. The effects of low- and high-frequency fatigue were studied in isometric conditions of muscle contraction. In addition to the well-known differentiation between low- and high-frequency fatigue effects, the complex pattern of efferent stimulation used allowed us to identify additional fatigue-related changes in the rate-tension hysteresis. This hysteresis seems to be one of the possible mechanisms directed to compensate for low-frequency fatigue in the muscle contraction.

Animals↗
PubMed2000

The role of cathepsin D and PAI-1 in primary invasive breast cancer as prognosticators and predictors of treatment benefit with adjuvant tamoxifen.

In the last few years there has been an increased interest in treatment predictive factors in breast cancer patients. The aim of the study was to analyse the role of cathepsin D and plasminogen activator inhibitor-1 (PAI-1) expression as independent prognosticators and to assess their predictive value with respect to tamoxifen treatment. This study comprises 1851 patients with primary breast cancer diagnosed during 1988-1992. Their median age was 62 years (range: 24-91). The end-point was distant disease recurrence-free interval. Adjuvant treatment with tamoxifen was given to 1136 patients (61%). The median follow-up time was 59 months (range: 39-88). Cathepsin D content was shown to be a significant independent prognosticator in multivariate Cox analysis (P=0.02). The optimal cut-off level was 10 fmol/mg protein, other cut-off levels did not improve the results. The level of cathepsin D also appeared to predict the benefit of tamoxifen among oestrogen receptor (ER)-positive patients although this result did not reach statistical significance (P=0.09). In a multivariate Cox analysis including 497 patients PAI-1 content was shown to be a significant independent prognosticator (P=0.003) but did not appear to predict the benefit of tamoxifen treatment. The optimal cut-off level appeared to be 3 ng/mg protein, which was close to the median value 2.5 ng/mg (range: 0-51). We conclude that cathepsin D is a significant independent prognosticator and may possibly also predict the benefit of tamoxifen amongst ER-positive patients. PAI-1 was also found to be a strong independent prognosticator but no treatment interaction with adjuvant tamoxifen was found.

Adult↗
PubMed2000

Reliability of position sense testing assessed with a fully automated system.

Position sense testing has increased as a tool for augmenting evaluation of joint injury. In the present study, we investigated the inter-day reliability for four different types of position sense tests using a fully automated system. The tests included (1) passive presentation/active replication, (2) passive presentation/passive replication, (3) semi-passive presentation/semi-passive replication (where semi-passive denotes passive movement during antagonist muscle contraction), and (4) active presentation/active replication. The absolute difference between presented target and replicated position was used as a measure of position sense accuracy. Ten healthy subjects who were blindfolded and seated with the arm in a moveable rig performed the tests on two occasions, separated by 3-4 days. For each type of position sense test, horizontal abduction from a starting position of 0 degrees (relative to the sagittal plane) to target positions of 32 degrees and 64 degrees, and horizontal adduction from a starting position of 80 degrees to 48 degrees and 16 degrees were conducted. A two-way ANOVA revealed no differences in absolute error between days or between testing procedures. However, intra-class correlations (ICC), which are most often used to express test-retest reliability, were moderate at best, ranging from 0.40 to 0.61 for the four types of position sense tests. Hence, the present study indicates that the ability of repositioning tests to detect alterations in proprioceptive function is limited, suggesting that their use in clinical evaluation be approached with prudence.

Adult↗
PubMed2000

A prospective population-based study of cutaneous malignant melanoma of the head and neck.

UNLABELLED: OBJECTIVES/HYPOTHESIS For cutaneous malignant melanoma (CMM) of the head and neck, neither prognostic factors in population-based groups, nor outcome with respect to surgical resection margins is clear. Therefore, we analyzed data in a regional registry to align treatment results for CMM of the head and neck with prognosis and survival times. STUDY DESIGN: Patient material collected prospectively for an 18-year period in a Swedish cancer registry underwent statistical analyses to establish the most reliable prognostic factors and the influence of surgical treatment on the survival of patients with CMM of the head and neck. METHODS: Data originated from the CMM database of the Stockholm-Gotland area of Sweden. Tumor thickness or invasiveness (Breslow or Clark's levels), extent of surgical margin, sex, histogenetic type, anatomic site, and ulceration were compared statistically for 469 patients. RESULTS: Male patients with head and neck CMM had a 68% 10-year survival rate; the 10-year survival rate for female patients was 87%. The corresponding figures for CMM at other sites were 83% and 90%, respectively. Tumor thickness (or Clark level of invasion) was the only statistically significant prognostic factor in a multivariate analysis (P < .001). The surgical resection margin seemed to be of no importance to outcome. CONCLUSIONS: Long-term survival after treatment for CMM of the head and neck is better than reported in most earlier publications, presumably because our evaluation used population-based materials, an important factor in accurate reporting of this kind. Tumor thickness is the main prognostic factor in estimating outcome.

Female↗
PubMed2000

Elevated intramuscular concentration of bradykinin in jaw muscle increases the fusimotor drive to neck muscles in the cat.

Patients suffering from temporomandibular dysfunction exhibit clinical findings such as fatigue, painful muscles, and muscles that are tender to palpation, not only in the temporomandibular area, but also in the neck/shoulder region. The mechanisms behind this are not known, although previous studies of similar spreading phenomena have revealed a possible involvement of the fusimotor system. In the present study, we evaluated the activity of this system by recording the activity of muscle spindle afferents from dorsal neck muscles after intramuscular injections of 6 microg to 25 microg bradykinin in the ipsilateral masseter muscle. A total of 23 muscle spindle afferents from the trapezius and splenius muscles was recorded at the C3-C4 level in 7 adult cats anesthetized with alpha-chloralose. Of these 23 afferents, 17 (74%) showed significantly different responses to bradykinin injections compared with control injections (dissolving agent, Tyrode), and the majority of the effects were compatible with an increased static fusimotor drive to the muscle spindle system. Thus, the results demonstrate potent reflex connections from groups III and IV masseter muscle afferents to fusimotor neurones on the C3-C4 level. It is concluded that the fusimotor system might play a significant role in the mechanisms behind the spread of muscle pain and tension from the temporomandibular region to the neck.

Afferent Pathways↗
PubMed1999

A technique for estimating activity in whole nerve trunks applied to the cervical sympathetic trunk, in the rabbit.

The changes in sympathetic outflow may be evaluated from the amplitude of the antidromic compound action potential (ACAP) according to the collision technique described by Douglas and Ritchie (Douglas, W.W. and Ritchie J.M., A technique for recording functional activity in specific groups of medullated and non-medullated fibers in whole nerve trunks. J. Physiol., 138(1957) 19-30). This technique was revised, taking into account the depressant action exerted by antidromic stimulation on sympathetic preganglionic neurones (SPNs). Cervical sympathetic nerve (CSN) of rabbits was used as experimental model. Stimulation frequencies of 0.2-0.5 Hz were found to be sufficiently low to avoid depressant actions on CSN spontaneous activity; they were employed to test the sensitivity of the technique during different experimental manoeuvres, such as changes in pulmonary-ventilation, baroreceptor unloading and arousal stimuli. In addition a procedure was devised to calibrate the ACAP amplitude: high frequency antidromic stimulation was used to induce a complete and transient inhibition of SPNs which allows to record the ACAP maximum amplitude. ACAPs recorded in various experimental conditions can then be expressed as percentage of this value.

Action Potentials↗