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Biomedical subjects

Frank Birklein

Publications and source records attributed to Frank Birklein.

33 records · Page 2Linked to original sources
PubMed2004

Chemically and electrically induced sweating and flare reaction.

Both thin afferent (nociceptors) and efferent (sympathetic sudomotor) nerve fibers can be activated electrically and chemically, resulting in neurogenic erythema and sweating. These reactions have been used before to assess the impairment of sympathetic and nociceptor fibers in humans. In this study, electrically induced sweating and erythema were assessed simultaneously in the foot dorsum and thigh, and were compared to chemically induced activation. Reproducible intensity-response relations (stimulation intensities 0-30 mA, 1 Hz) were obtained from 32 subjects. The steepest increase of the sweat response was induced at lower intensities as compared to that of the erythema (18.3 mA vs. 25.7 mA, p<0.01) and reached a plateau for intensities above 25 mA, suggesting lower electrical thresholds for sudomotor fibers. Maximum flare areas induced electrically with 30 mA were smaller than those evoked chemically (flare size: 4.5 cm2 vs. 10.6 cm2). In contrast, the electrically evoked sweating rate was higher than that evoked chemically (acetylcholine, or ACh; sweating rate 0.31 vs. 0.21 microl/cm2/min, p<0.01), which might be attributed to an increased effectiveness of synchronized discharge in sympathetic fibers upon electrical stimulation.

Acetylcholine↗
PubMed2004

Facilitated neurogenic inflammation in unaffected limbs of patients with complex regional pain syndrome.

Pain, edema, increased skin temperature, reddening and trophic changes characterize complex regional pain syndrome (CRPS). Recently, we have been able to show facilitated neurogenic inflammation on the affected limb. In the current study unaffected limbs were examined after resolution of the CRPS symptoms to assess possible generalized changes predisposing to CRPS. In 12 patients and in 12 healthy volunteers dermal microdialysis in combination with electrical C-fiber stimulation was employed to induce neuropeptide release. Dialysate protein concentration and axon reflex vasodilation were measured. Neither in patients nor in controls did electrical stimulation lead to protein extravasation, while axon reflex vasodilation was significantly enhanced even on the patients' unaffected limbs (P < 0.05). Our results support the hypothesis that facilitated neurogenic inflammation is a predisposing factor for CRPS. The lack of protein extravasation indicates that an initiating trauma is necessary to induce neuropeptide up-regulation in primary afferents.

Adult↗
PubMed2004

Comparison of continuous wave Doppler ultrasound of the radial artery and laser Doppler flowmetry of the fingertips with sympathetic stimulation.

Laser Doppler is widely used to evaluate sympathetic vasoconstrictor function. Continuous wave (cw)-Doppler of the radial artery may be an alternative but less expensive approach to quantify sympathetically induced resistance changes in the peripheral vascular system. In order to compare the power of both methods, this study was performed with simultaneous assessment of cw Doppler and laser Doppler flowmetry in volunteers. Twenty-five healthy subjects (median age years, range 20-27) rested in a relaxed supine position and were asked to perform a deep inspiratory gasp and a commanded cough (DIG + C). Radial artery blood flow was assessed with a standard cw Doppler device, arteriolar blood flow was assessed simultaneously employing a single point laser Doppler perfusion monitor at the fingertips. We quantified the latency between stimulus and onset of vasoconstriction, the latency to the maximum vasoconstriction and the duration of response. The decrease in flow velocities (cw Doppler) after stimulus was compared with the decrease in capillary flow (laser Doppler). While the flow profile as measured with laser Doppler remained monophasic after stimulation, cw Doppler showed biphasic flow (or absent diastolic flow) in all subjects after DIG + C. The latencies between stimulus and onset of reaction were significantly shorter when measured with laser Doppler (1.8 s vs. 2 s, p = 0.049), the latencies till the maximum extent of the reaction was reached did not differ significantly (3.2 vs. 3.3 s). The duration of the response was significantly shorter when measured by laser Doppler (12.0 vs. 14.5 s (p < 0.0001). While skin blood flow in the laser Doppler measurement decreased after stimulation from 654 flux units (FU) to 319 FU (-59%), mean flow velocities in the radial artery declined from 1.07 kHz to 0.14 kHz (-87%). This relative change was significantly different (p < 0.0001). The correlation between the decline of flux units as measured by laser Doppler and cw Doppler changes was r = 0.616 (p = 0.004). Both methods are feasible to monitor flow changes due to sympathetic stimulation. Latencies and relative quantitative changes were closely correlated.Thus, cw Doppler is a valid alternative approach to laser Doppler flowmetry in healthy volunteers.

Adult↗
PubMed2004

Catecholamine release in human skin--a microdialysis study.

Dermal microdialysis might be a promising tool to investigate properties of sympathetic neurons in the skin as investigation of peripheral noradrenergic neurons in humans usually relies on highly variable vasoconstrictor reflexes or on indirect measurements like skin temperature recordings. To evaluate this technique, 21 experiments were performed in 15 healthy subjects with four intracutaneous microdialysis fibers (diameter, 200 microm; cutoff, 5 kDa) at hands or feet. After 60 min, saline perfusion tyramine at concentrations of 0.195 to 200 microg/ml was applied for 15 min followed by a 15-min saline perfusion again. Catecholamine concentrations were detected through high-performance liquid chromatography with electrochemical detection. Control experiments were performed in human skin homogenates with and without tyramine incubation. In vivo, norepinephrine (NE) concentration increased from 36.3 +/- 10.2 pg/ml to 84.4 +/- 18.4 pg/ml (P < 0.001) during stimulation with tyramine, dialysate dopamine (DA) concentration increased from 105.2 +/- 36.5 pg/ml to 7162.4 +/- 3972.4 pg/ml (P < 0.001). Both tyramine-induced NE and DA release were dose-dependent (NE: r = 0.438, P < 0.05; DA: r = 0.894, P < 0.001). In skin homogenates, tyramine incubation led to a significant increase of DA concentrations (387.0 +/- 34.8 pg/ml, controls: 13.2 +/- 2.4 pg/ml; P < 0.05), while NE and epinephrine levels remained unchanged. In conclusion, our experiments show that dermal microdialysis is capable of locally measuring catecholamines in human skin. This offers the opportunity to investigate the function of the peripheral sympathetic nervous system. Additional to non-enzymatic oxidation, DA increase probably reflects metabolic degradation of tyramine by non-neuronal pathways and therefore does not reflect local sympathetic innervation.

Adult↗
PubMed2004

Electrically stimulated axon reflexes are diminished in diabetic small fiber neuropathies.

Axon reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic axon reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, electrical thresholds for flare induction were increased (thighs P < 0.001 and feet P < 0.03). In NO-Ns, flare size at the feet (P < 0.02) and flux at both sites (thighs P < 0.001 and feet P < 0.002) were even increased. Test/retest evaluation of our method revealed a good correlation (r = 0.83, P < 0.004). Intracutaneous electrical stimulation of C-fibers and scanning the flare with LDI is a sensitive tool to reliably detect small fiber impairment in diabetic SFN subjects and even increased neuropeptide release in NO-Ns.

Adult↗
PubMed2004

Thermal thresholds predict painfulness of diabetic neuropathies.

OBJECTIVE: Pathophysiology explaining pain in diabetic neuropathy (DN) is still unknown. RESEARCH DESIGN AND METHODS: Thirty patients with peripheral DN (17 men and 13 women; mean age 52.4 +/- 2.5 years) were investigated. Fifteen patients had neuropathic pain, and 15 patients were free of pain. Patients were followed over 2 years and examined at the beginning and thereafter every 6 months. Clinical severity and painfulness of the DN were assessed by the neuropathy impairment score and visual analog scales (VASs). Cold and warm perception thresholds as well as heat pain thresholds were obtained for evaluation of Adelta- and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were recorded for analysis of thickly myelinated fibers. Moreover, for assessment of cardiac vagal function, heart rate variability (HRV) was evaluated. In order to reduce day-to-day variability of pain, mean values of the five time points over 2 years were calculated and used for further analysis. Data were compared with an age- and sex-matched control group of healthy volunteers. RESULTS: There were significant differences regarding electrophysiological studies, HRV and quantitative sensory testing (QST) between patients and healthy control subjects (P < 0.001). Generally, patients with neuropathic pain were indistinguishable from pain-free patients. In the pain group, however, VAS pain ratings were correlated to the impairment of small-fiber function (cold detection thresholds, P = 0.02; warm detection thresholds, P = 0.056). CONCLUSIONS: Intensity of pain in painful DN seems to depend on small nerve fiber damage and deafferentation.

Case-Control Studies↗
PubMed2003

Patterns of cortical reorganization in complex regional pain syndrome.

OBJECTIVE: To use magnetoencephalography to assess possible cortical reorganization in the primary somatosensory cortex (S1) of patients with complex regional pain syndrome (CRPS). BACKGROUND: Patterns of pain and sensory symptoms in CRPS may indicate plastic changes of the CNS. METHODS: Magnetic source imaging was used to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 12 patients. RESULTS: The authors found a significant shrinkage of the extension of the cortical hand representation for the CRPS affected side. The center of the hand was shifted toward the cortical representation of the lip. The cortical reorganization correlated with the amount of CRPS pain (r = 0.792), as measured by the McGill questionnaire, and the extent of mechanical hyperalgesia (r = 0.860). Using multiple regression analysis, the best predictor for the plastic changes was found to be mechanical hyperalgesia. Additionally, S1 sources following tactile stimulation were significantly increased on the CRPS side compared to the unaffected limb. CONCLUSIONS: This study showed reorganization of the S1 cortex contralateral to the CRPS affected side. The reorganization appeared to be linked to complaints of neuropathic pain.

Adult↗
PubMed2003

No alpha-adrenoreceptor-induced C-fiber activation in healthy human skin.

In healthy volunteers, flare responses induced by norepinephrine (NE) iontophoresis have been observed. However, as NE iontophoresis is a combined electrical and chemical stimulus axon, reflexes cannot be directly linked to pharmocological activity of NE. Different concentrations of NE, clonidine (CL), and phenylephrine (PE) (NE: 10(-10)-10(-3) M; CL and PE: 10(-8)-10(-3) M) were applied via intradermal microdialysis fibers into the skin of healthy volunteers. Simultaneously, skin blood flow was visualized by laser-Doppler imaging scans and quantified in a vasoconstriction skin area directly above the membranes to control drug effects and in expected axon reflex vasodilation areas that were 0.75 cm apart. NE, PE, and CL caused dose-dependent vasoconstriction. However, neither in the presumed axon reflex areas (quantitative analysis) nor on laser-Doppler imaging pictures (qualitative analysis) were any vasodilation observed. Even at concentrations causing maximum vasoconstriction (10(-3) M for any drug), no vasodilation was induced. Our results indicate that, in healthy human skin, exogenously supplied alpha-adrenoreceptor agonists alone do not activate nociceptors sufficiently to induce axon reflex flare.

Adrenergic alpha-Agonists↗
PubMed2003

Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome.

Pain, mechanical hyperalgesia, edema, increased skin temperature, and skin reddening are characteristic symptoms of acute complex regional pain syndrome (CRPS). We have recently demonstrated facilitated neurogenic inflammation on the affected limb. To further elucidate the underlying mechanisms, exogenous substance P (SP) in ascending concentrations (10(-9), 10(-8), 10(-7), 10(-6) M) was intradermally applied to the affected and the unaffected limbs, respectively, in two groups of 11 CRPS patients each using the microdialysis technique. Fourteen healthy volunteers served as controls for SP application, and 9 volunteers and 10 patients served as controls for saline perfusion. Dialysate protein content was measured photometrically to assess plasma protein extravasation. Significant differences in dialysate protein content were found after 10(-9) M SP (affected side, 98.4 +/- 8.4% of baseline value; unaffected side, 104.4 +/- 5.6%; controls, 70.7 +/- 4.1%; P < 0.005) and after 10(-6) M SP (affected, 169.7 +/- 24.2%; unaffected, 189.4 +/- 19.1%; controls, 122.2 +/- 12.0%; P < 0.05). While 10(-9) M SP induced no protein extravasation in controls, it provoked protein extravasation in 6 of 11 patients on the affected and in 5 of 11 patients on the unaffected side (P < 0.01). We conclude that SP-induced plasma protein extravasation is increased in CRPS patients on both the affected and unaffected limbs. The underlying mechanism might be impaired SP inactivation. Thus, our results further support the hypothesis that neurogenic inflammation plays an important role in the initiation of CRPS.

Adult↗
PubMed2003

Botulinum toxin type B blocks sudomotor function effectively: a 6 month follow up.

This study analyzes the suppression of sweat gland activity by botulinum toxin type B. We injected botulinum toxin type B (between 2 and 1000 mouse units subcutaneously) in the lateral side of both lower legs in 15 healthy volunteers. Sweat tests were carried out before botulinum toxin type B injections, and at 3 wk, 3 mo, and 6 mo. We studied focal anhidrosis by iodine-starch staining and by capacitance hygrometry after carbachol iontophoresis, according to the quantitative sudomotor axon reflex test (QSART). Iodine starch staining indicated that a threshold dose of 8 mouse units botulinum toxin type B leads to anhidrotic skin spots (>4 cm2) after 3 wk. Duration of anhidrosis was prolonged for 3 mo when 15 mouse units and for 6 mo when 125 mouse units botulinum toxin type B were injected. The size of the anhidrotic area decreased with time (p<0.001), indicating partial recovery at the edges. After 3 wk, the QSART score had significantly decreased to 18% of baseline and had decreased to zero in most subjects with doses of 62.5 mouse units or more. After 3 mo, the QSART had returned to 91% of baseline in all but one subject and, after 6 mo, recovery of sudomotor function was complete. Analysis by iodine-starch staining and QSART indicated that botulinum toxin type B suppresses sudomotor function effectively, in a concentration-dependent manner.

Botulinum Toxins↗
PubMed2003

Micro-lightguide spectrophotometry as an intraoral monitoring method in free vascular soft tissue flaps.

PURPOSE: The aim of this prospective study was to measure the hemoglobin oxygen saturation (HbO(2)%) and relative Hb concentration of free vascular soft tissue flaps using micro-lightguide spectrophotometry. The objective was to measure the normal range and topographic differences in HbO(2)% and rel. Hb conc. in tissue transfers before establishing this as a clinical method for monitoring perfusion and vitality. PATIENTS AND METHODS: In 39 patients who had received free vascular soft tissue flaps (34 radial forearm flaps; 8 latissimus flaps) to cover defects after tumor surgery, the capillary HbO(2)% in transferred tissue was measured spectrophotometrically preoperatively at the donor site and postoperatively up to the third postoperative day. On average about 500 hemoglobin spectra (200 to 800 spectra) were measured over each 24-hour period. Additionally, the relative Hb concentration was determined for the individual measuring times. The measurements were carried out topographically on the flap base, flap center, and flap periphery. RESULTS: The preoperative HbO(2) values at the donor site of free soft tissue flaps were between 20% and 40% in all topographic regions. In the case of clinically successful flaps, a normal distribution of the HbO(2) values of 20% to 80% was obtained in the immediate postoperative period, and from the second day on, a normal distribution of 45% to 60%. In the case of 2 flaps with partial necrosis, HbO(2) values of less than 10% to 15% were measured from the second postoperative day on. The relative Hb concentration had no influence on the amount of HbO(2)% measured in the transferred capillaries. In the postoperative phase, here was no topographic difference between the individual flap regions. CONCLUSIONS: As a noninvasive method, micro-lightguide spectrophotometry permits quantitative determination of HbO(2)% and relative Hb concentration over the entire surface of soft tissue flaps. In the case of partially unsuccessful flaps, HbO(2) values of less than 10% to 15% were measured beforehand, thus indicating that these HbO(2) values are not sufficient to support the vitality of the free tissue transfer. When combined with clinical observation, application can be recommended for the vitality measurement of free soft tissue flaps and permits more information to be obtained on topographic capillary perfusion conditions.

Adolescent↗
PubMed2002

Sudomotor testing predicts the presence of neutralizing botulinum A toxin antibodies.

The increasing number of patients being treated with botulinum toxin A complex (BoNT/A) has led to a higher incidence of neutralizing anti-BoNT/A antibodies (ABAs). Because BoNT/A is known to inhibit sweating, here we report sudometry as a possibility for predicting the presence of ABA. Sixteen patients suffering from spasmodic torticollis were selected: in 2 patients, BoNT/A treatment continued to be effective, in 9 patients, the treatment effect was impaired, and in 5 patients, secondary treatment failure developed. BoNT/A (100 mouse units, Dysport; Ipsen Pharma, Berkshire, United Kingdom) was injected subcutaneously into the lateral calves. Sweating was visualized with iodine starch staining. In addition, quantitative sudomotor axon reflex testing was performed at the injection site. Individual ABA titers were determined with a mouse bioassay. Results of sudometry significantly correlated with the BoNT/A treatment success. The quantitative sudomotor axon reflex testing was 0.58 +/- 0.63 fraction of the normal mean in patients with treatment failure, 0.18 +/- 0.13 fraction of the normal mean in those who responded partially, and 0 in responders (p < 0.01). Accordingly, the areas of the anhidrotic skin after subcutaneous injections were 4.5 +/- 10.3 cm(2), 32.7 +/- 16.5 cm(2), and 62 cm(2) (p < 0.01). Discrimination analysis indicated that the presence of ABA (6 ABA-positive and 10 ABA-negative) could be predicted correctly in all patients from the results of sudometry. Therefore, sudometry is a useful tool for identifying patients with neutralizing ABAs and might be helpful for identifying reasons for BoNT/A treatment failure.

Adult↗
PubMed1998

Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome.

Twenty patients suffering from complex regional pain syndrome (CRPS) and 21 healthy control subjects were examined to evaluate sympathetic reflex vasoconstriction. The mean age of the 12 female and eight male patients was 48.9 (21-72) years. At the time of investigation the median duration of the disease was 8.5 weeks (2-70). Twenty-one healthy subjects were investigated for control. Different maneuvers, such as the veno-arteriolar reflex (VAR), inspiratory gasp (IG), cold pressor test (CP) and mental arithmetic (MA), were employed to induce vasoconstriction while the cutaneous blood flow of the affected and the contralateral limb was recorded. In addition, the skin temperature of both limbs was measured by infrared thermography. In 14 of 20 patients and in 14 of 21 control subjects vasoconstriction due to the provocation tests could be measured, while the remaining six patients and seven controls showed vasodilatation in at least one test, and by that they were excluded from analysis of vasoconstrictor reflex pattern. After thermoregulatory adaptation skin temperature was not different between the affected and the unaffected limb. Sympathetic reflex vasoconstriction triggered by MA which represents cortical generated, moderate vasoconstrictor stimulus, was significantly reduced on the affected limb (102.9% of prestimulus period) when compared to the control limb (85.0%, P < 0.002) or to controls (84.8%, P < 0.001). VAR (pure postganglionic), IG and CP (both spinal and supraspinal), representing stronger vasoconstrictor stimuli, revealed no significant side to side difference of sympathetic vasoconstriction and no significant difference as compared to controls. In conclusion our findings prove impairment of sympathetic vasoconstrictor activity after central vasoconstrictor stimulation in CRPS, and possible mechanisms are discussed.

Adult↗