The primary (SI) and secondary (SII) somatosensory cortices have been shown to participate in human pain processing. However, in humans it is unclear how SI and SII contribute to the encoding of nociceptive stimulus intensity. Using magnetoencephalography (MEG) we recorded responses in SI and SII in eight healthy humans to four different intensities of selectively nociceptive laser stimuli delivered to the dorsum of the right hand. Subjects' pain ratings correlated highly with the applied stimulus intensity. Activation of contralateral SI and bilateral SII showed a significant positive correlation with stimulus intensity. However, the type of dependence on stimulus intensity was different for SI and SII. The relation between SI activity and stimulus intensity resembled an exponential function and matched closely the subjects' pain ratings. In contrast, SII activity showed an S-shaped function with a sharp increase in amplitude only at a stimulus intensity well above pain threshold. The activation pattern of SI suggests participation of SI in the discriminative perception of pain intensity. In contrast, the all-or-none-like activation pattern of SII points against a significant contribution of SII to the sensory-discriminative aspects of pain perception. Instead, SII may subserve recognition of the noxious nature and attention toward painful stimuli.

Adult↗

PubMed2001

Behavioural relevance modulates access to spatial working memory in humans.

Neurophysiological studies in monkeys suggest selective representation of behaviourally relevant information in working memory. So far, no behavioural evidence for this has been reported for humans. Here, we investigated the role of behavioural relevance for access to human visuospatial working memory by using delayed oculomotor response tasks. Subjects were presented two successive visual cues in different and unpredictable locations while fixating on a central fixation point. After a delay, an unpredictable auditory signal (one beep or two beeps) sounded and the central fixation point was turned off, initiating the oculomotor response (i.e. memory-guided saccade) phase. Two groups of 10 subjects each were studied in two conditions: in the 'relevant' condition, subjects were instructed to memorize both visual cues and to move the eyes to the remembered position of the first cue (one beep) or the second cue (two beeps). The same stimuli were used in the 'irrelevant' condition, but subjects were instructed to memorize and move the eyes to the position of the first cue only, regardless of the second cue and the auditory signal. In the 'relevant' condition, we found a significant increase in errors of memory-guided saccades to the first cue, when the second cue was located between central fixation point and first cue. This spatially selective interference effect disappeared in the 'irrelevant' condition, despite identical stimuli. On a behavioural level, these results show for the first time the significance of behavioural relevance for access to human spatial working memory. These findings complement recent single-neuron studies in monkeys, showing that the neuronal substrates of working memory selectively represent behaviourally relevant perceptual information.

Adult↗

PubMed2000

Separate representations of static and dynamic touch in human somatosensory thalamus.

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Adult↗

PubMed2000

Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines.

BACKGROUND: The aim of this retrospective single center analysis was to compare possible long-term benefits of two different rabbit-antithymocyte globuline (ATG) induction therapies after cardiac transplantation. PATIENTS AND METHODS: A total of 484 primary cardiac transplanted patients received induction therapy with two different rabbit-ATGs (thymoglobuline: n=342, ATG-fresenius: n=142). All patients received immunosuppressive maintenance therapy with cyclosporine, azathioprine, and prednisolone. Cardiac rejection was assessed by serial endomyocardial biopsies. Surveillance of graft arteriosclerosis was performed by angiograms 1, 3, and 5 years after transplantation. RESULTS: Five-year survival was significantly better in the thymoglobuline group (76 vs. 60%). Thymoglobuline patients had a lower rate of death from rejection (2.3 vs. 10%; P<0.01) and graft arteriosclerosis (0.88 vs. 5.6%; P<0.01). After 5 years, freedom from rejection was 72% in the thymoglobuline group compared to 42% in the ATG-fresenius group (P<0.01). Graft arteriosclerosis appeared in 14% of thymoglobuline patients and in 28% of ATG-fresenius patients (P<0.01). Viral infections occurred more often in thymoglobuline patients (53 vs. 39%, P<0.05) although there was no difference in appearance of cytomegalovirus disease (17 vs. 13%). Freedom from posttransplant malignant disease was comparable between the two groups. CONCLUSION: These results suggest that there are differences between rabbit ATG products. The superior prevention of rejection with thymoglobuline may be the reason for the lower rate of graft arteriosclerosis.

Adolescent↗

PubMed2000

Significance of right bundle branch block in the diagnosis of myocardial ischemia in patients undergoing coronary artery bypass grafting.

BACKGROUND: Perioperative diagnosis of myocardial ischemia following cardiac surgical procedures remains a challenging problem. Particularly, the role of new conduction disturbances as markers of postoperative ischemia is still questionable. The goal of this study was to elucidate the diagnostic significance of new postoperative right bundle branch block (RBBB) for the detection of perioperative myocardial ischemia in patients undergoing elective coronary artery bypass grafting (CABG). METHODS: In 169 consecutive patients, three-channel Holter monitoring and serial assessment of serum enzymes were performed for 48 h, and 12-lead ECG repeated for up to 5 days postoperatively. Postoperative events were classified as either myocardial infarction (MI), transient ischemic events (TIE) or various conduction disturbances. RESULTS: Transient (n=9) or permanent (n=4) RBBB occurred in 13 patients (8%); 14 patients (8%) showed signs of perioperative MI and 18 patients (11%) evidence of TIE. Peak activity of creatine-kinase (CK, 561+/-135 vs. 316+/-19, P<0.05) and CK-MB (22.7+/-3.2 vs. 13.4+/-0.8, P<0.01) were higher in patients with RBBB than in patients without perioperative ischemic events. Peak CK-MB levels were significantly higher in patients with MI as compared to those with RBBB (33.4+/-7.6 vs. 22.7+/-3.2, P<0. 05). Patients with TIE had similar perioperative enzyme levels as patients with no events. CONCLUSION: It is concluded that the combined assessment of repeated 12-lead ECG, continuous Holter monitoring and enzyme analysis allows a reliable diagnosis of perioperative myocardial ischemia and conduction disturbances. The occurrence of new RBBB following elective CABG is indicative of perioperative myocardial necrosis and thus serves as a valuable tool for the diagnosis of new, perioperative ischemic events.

Biomarkers↗

PubMed2000

Is long-term functional outcome after lung volume reduction surgery predictable?

OBJECTIVE: The aim of this retrospective study was to analyze which preoperative parameters might predict a persistent improvement in forced expiratory volume in 1 s (FeV1) 1 year after surgery. METHODS: Seventy consecutive lung volume reduction surgery (LVRS) patients (age, 56.5+/-1.2 years) with a follow-up period of at least 1 year were analyzed (from September 1994 to September 1997). The patients were described by lung function tests, blood gas analysis, ventilatory mechanics (intrinsic positive endexpiratory pressure (PEEP)) and morphometric data (degree of heterogeneity, DHG; degree of hyperinflation, DHI; severity of parenchymal destruction, SPD) preoperatively. Based on the postoperative course of FeV1 (percentual increase compared with preoperative values, % increase), patients were divided into four groups: group A, (n=21) no improvement (FeV1</=20% increase); group B, (n=10) FeV1>/=20% increase, which declined to preoperative values after 1 year; group C, (n=18) FeV1, 20-40% increase, sustaining at 1 year; group D, (n=21) FeV1>/=40% increase, sustaining at 1 year. The statistics comprised of analysis of variance (ANOVA) and chi-square testing, with values presented as means+/-SEM. RESULTS: No differences were found for lung function parameters (FeV1: 27.7+/-2.7, 26.0+/-2.5, 23. 9+/-2.2 and 23.9+/-1.9% predicted, in groups A, B, C and D, respectively). Arterial blood gas levels preoperatively revealed significant differences between the groups; the arterial pO(2) was 66.2+/-1.2 mmHg in groups A+B compared with 61.8+/-1.5 mmHg in groups C+D (P=0.030). The arterial pCO(2) was 39.2+/-1.1 mmHg in groups A+B compared with 43.3+/-1.5 mmHg in groups C+D (P=0.038). The morphometric data had a strong trend towards higher heterogeneity in groups C and D. Marked DHI was found in 59 and 81% of patients in groups A+B versus C+D, respectively (P=0.121). Marked DHG was present in 22 and 54% of patients in groups A+B versus C+D, respectively (P=0.010). CONCLUSION: Preoperative arterial pO(2) and pCO(2), and the DHG are predictors for long-term benefit after LVRS with regard to the FeV1, 1 year postoperatively.

Analysis of Variance↗

PubMed2000

Communication: papillomavirus DNA in basal cell carcinomas of immunocompetent patients: an accidental association?TITLE.

DNA of human papillomaviruses has frequently been detected in nonmelanoma skin cancers, raising the question of a possible causal contribution of these tumor viruses to skin carcinogenesis. Basal cell carcinomas are the most common nonmelanoma skin cancers; however, so far they are only poorly analyzed with regard to human papillomavirus infection. We searched for human papillomavirus-DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two geographic locations in Europe using six different polymerase chain reaction primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the tested tumors. Human papillomavirus positivity did not seem to correlate with the duration of disease or patients' age. The vast majority of virus types in the biopsies belonged to the group of epidermodysplasia verruciformis-associated human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in tumors as well as in perilesional healthy skin, seven carried viral sequences in lesional and healthy skin and three only in the basal cell carcinoma. Six of the seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs contained identical human papillomavirus types in tumors and histologically normal tissue. Forty basal cell carcinoma patients were additionally analyzed for IgG antibodies against virus-like particles of three representative epidermodysplasia verruciformis-human papillomavirus types: 8, 15, and 36. No statistically significant differences could be detected between human papillomavirus antibody prevalences of basal cell carcinoma patients and of dermatologically healthy individuals. Moreover, serologic findings did not correlate with the detection of specific human papillomavirus types in tumors. Our results seem to suggest that the occurrence of human papillomavirus-DNA in basal cell carcinoma does not reflect a major etiologic role of human papillomavirus in this cancer.

Aged↗

PubMed2000

Neurophysiology and functional neuroanatomy of pain perception.

The traditional view that the cerebral cortex is not involved in pain processing has been abandoned during the past decades based on anatomic and physiologic investigations in animals, and lesion, functional neuroimaging, and neurophysiologic studies in humans. These studies have revealed an extensive central network associated with nociception that consistently includes the thalamus, the primary (SI) and secondary (SII) somatosensory cortices, the insula, and the anterior cingulate cortex (ACC). Anatomic and electrophysiologic data show that these cortical regions receive direct nociceptive thalamic input. From the results of human studies there is growing evidence that these different cortical structures contribute to different dimensions of pain experience. The SI cortex appears to be mainly involved in sensory-discriminative aspects of pain. The SII cortex seems to have an important role in recognition, learning, and memory of painful events. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in affective aspects of pain-related learning and memory. The ACC is closely related to pain unpleasantness and may subserve the integration of general affect, cognition, and response selection. The authors review the evidence on which the proposed relationship between cortical areas, pain-related neural activations, and components of pain perception is based.

Animals↗

PubMed2000

Differential organization of touch and pain in human primary somatosensory cortex.

Processing of tactile stimuli within somatosensory cortices has been shown to be complex and hierarchically organized. However, the precise organization of nociceptive processing within these cortices has remained largely unknown. We used whole-head magnetoencephalography to directly compare cortical responses to stimulation of tactile and nociceptive afferents of the dorsum of the hand in humans. Within the primary somatosensory cortex (SI), nociceptive stimuli activated a single source whereas tactile stimuli activated two sequentially peaking sources. Along the postcentral gyrus, the nociceptive SI source was located 10 mm more medially than the early tactile SI response arising from cytoarchitectonical area 3b and corresponded spatially to the later tactile SI response. Considering a mediolateral location difference between the hand representations of cytoarchitectonical areas 3b and 1, the present results suggest generation of the single nociceptive response in area 1, whereas tactile stimuli activate sequentially peaking sources in areas 3b and 1. Thus nociceptive processing apparently does not share the complex and hierarchical organization of tactile processing subserving elaborated sensory capacities. This difference in the organization of both modalities may reflect that pain perception rather requires reactions to and avoidance of harmful stimuli than sophisticated sensory capacities.

Adult↗

PubMed1999

Pain affect without pain sensation in a patient with a postcentral lesion.

We report findings from clinical examination and cutaneous laser stimulation in a 57-year-old male, who suffered from a right-sided postcentral stroke. In this patient, we were able to demonstrate (i) a dissociation of discriminative and affective components of pain perception and, for the first time in humans, (ii) the dependence of sensory-discriminative pain component and first pain sensation on the integrity of the lateral pain system.

Affect↗

PubMed1999

Parallel activation of primary and secondary somatosensory cortices in human pain processing.

Cerebral processing of pain has been shown to involve primary (SI) and secondary (SII) somatosensory cortices. However, the temporal activation pattern of these cortices in nociceptive processing has not been demonstrated so far. We therefore used whole-head magnetoencephalography to record cortical responses to cutaneous laser stimuli in six healthy human subjects. By using selective nociceptive stimuli our results confirm involvement of contralateral SI and bilateral SII in human pain processing. Beyond they show for the first time simultaneous activation onset of contralateral SI and SII after approximately 130 ms, indicating parallel thalamocortical distribution of nociceptive information. This contrasts to the serial cortical organization of tactile processing in higher primates and instead corresponds to the parallel cortical organization in lower primates and nonprimates. Thus our finding suggests preservation of the basic mammalian parallel organizational scheme in human pain processing, whereas in the tactile modality parallel organization appears to be abandoned in favor of a serial processing scheme. Functionally, preservation of direct access to SII underscores the relevance of this area in human pain processing, probably reflecting an important role of SII in nociceptive learning and memory.

Adult↗