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H C Pape

Publications and source records attributed to H C Pape.

At least 55 records · Page 3Linked to original sources
PubMed2000

Putative cortical and thalamic inputs elicit convergent excitation in a population of GABAergic interneurons of the lateral amygdala.

Synaptic circuitry in the rat lateral amygdala (AL) was studied in brain slices using electrophysiological recordings. Electrical stimulation of external and internal capsules evoked an EPSC followed by a sequence of GABA(A) and GABA(B) receptor-mediated IPSC in principal neurons. Paired stimulation of either afferents resulted in a significant reduction ( approximately 45%) of the second GABA(A) receptor-mediated IPSC. A priming stimulation, consisting of a priming pulse to one pathway followed by a pulse to the other pathway, resulted in a strong depression of the second IPSC basically identical to that during paired stimulation. Paired- and primed-pulse depressions were largely relieved by 10 micrometer CGP 55845A, indicating regulation through presynaptic GABA(B) receptors. Furthermore, putative interneurons responded with EPSCs of constant latencies to minimal stimulation of both cortical and thalamic fibers, indicating convergent monosynaptic input. At higher stimulation strength, an approximately 15% reduction of EPSCs occurred in interneurons after paired and primed stimulation, which was not sensitive to CGP 55845A. These findings indicate that a rather homogeneous population of interneurons exists in the AL with respect to their afferent connectivity, in that they receive convergent input through putative thalamic and cortical fibers, both directly and indirectly (through principal neurons), and mediate inhibitory control of postsynaptic principal neurons. This symmetrically built GABAergic circuitry can be of functional significance, given the distinctive role of the two afferent input systems for the mediation of different components of fear responses and the importance of GABAergic mechanisms for limitation of excessive neuronal activity.

Afferent Pathways↗
PubMed2000

Synaptic mechanisms of NMDA-mediated hyperpolarization in lateral amygdaloid projection neurons.

Synaptic mechanisms underlying NMDA-mediated responses of neurons in the guinea pig lateral amygdala (AL) were investigated in in vitro slice preparations. Local application of NMDA resulted in initial hyperpolarization of pyramidal-like spiny cells (projection neurons), followed by prolonged depolarization. The slow depolarization represented a direct postsynaptic effect of NMDA, whereas the initial hyperpolarization was induced presynaptically through activation of GABAergic interneurons and was sensitive to blockade by tetrodotoxin as well as the GABA(A)-receptor antagonist bicuculline. Application of NMDA resulted in AP-5-sensitive, lasting depolarization also in putative interneurons of the AL suggesting direct activation of GABAergic interneurons by NMDA. These data indicate that interneurons in the rat lateral amygdala possess functional NMDA receptors, which may contribute to the predominantly inhibitory synaptic responses in amygdaloid neurons following activation through afferent input systems.

Action Potentials↗
PubMed2000

Spike doublets in neurons of the lateral amygdala: mechanisms and contribution to rhythmic activity.

A majority of projection neurons in the lateral amygdala generate oscillatory spike firing in the theta-frequency range, largely due to intrinsic membrane properties. Here we report on the occurrence of spike doublets in about 70% of these cells. Spike doublets consisted of a fast initial and a second slower component, which were mediated by sodium- and calcium-dependent mechanisms, respectively. With increased level of depolarization, there was a gradual transition of fast action potentials, regular alternation of fast action potentials and spike doublets, regular spike doublets, and high-threshold oscillations. Fast Fourier transforms demonstrated the rhythmic nature of spike doublets at around 3 Hz with an intra-doublet frequency of 25-80 Hz. Spike doublets may thus contribute to the overall rhythmicity in the membrane potential patterns of projection cells and support the integration of synaptic input signals.

Action Potentials↗
PubMed2000

Input-specific long-term depression in the lateral amygdala evoked by theta frequency stimulation.

Although conditioned fear has been shown to involve mechanisms of synaptic plasticity in the amygdala, the association with afferent input systems is not yet clear. Here we report on homosynaptic long-term depression (LTD) of excitatory responses after stimulation of putative thalamic input fibers, but not of cortical inputs, to the rat lateral amygdala in vitro. LTD is induced by theta frequency stimulation and involves postsynaptic calcium-dependent mechanisms and group II metabotropic glutamate receptors. These input-specific changes in synaptic strength represent potential cellular sources, which regulate the balance between sensory thalamic and cortical input signals to the amygdala. This regulation would function to reduce the influence of relatively undiscriminated stimulus information carried by thalamic afferents in favor of discriminated sensory information mediated by the cortex during fear responses.

Amygdala↗
PubMed2000

Activity-related changes in intracellular pH in rat thalamic relay neurons.

Activity-related shifts in intracellular pH (pHi) can exert potent neuromodulatory actions. Different states of neuronal activity of thalamocortical neurons were found to differentially modulate pHi. Tonic activity evoked by injection of depolarizing current led to a reversible rise in [H+]i which was nearly abolished in the presence of TTX. Block of voltage-gated calcium channels with I mM Ni2+ reduced the [H+]i transients related to tonic activity. Rhythmic activation of burst discharges caused changes of [H+]i which were decreased by TTX, whereas I mM Ni2+ almost abolished the [H+]i transients. The present results show that different forms of neuronal activity can lead to intracellular acidification caused by different mechanisms, i.e. Na+ and Ca2+ influx through sodium and Ca2+ channels, respectively, and the subsequent activation of a Ca2+/H+ pump. The resulting acidosis is suggested to reduce further Ca2+ influx and prevent excessive neuronal excitation.

Acidosis↗
PubMed2000

[Post-traumatic osteolysis of the distal clavicle. A case report and review of the literature]].

The post-traumatic osteolysis of the distal clavicle is very infrequent and the etiology and pathology is poorly understood. It is important to consider this possibility for differential diagnosis when continued pain in the acromio-clavicular joint (AC joint) follows blunt shoulder trauma. The course of the disease may result in a 3 cm loss of length of the distal clavicle. Months and years may pass until osteolysis becomes manifest, but the earliest radiological findings are present 4 weeks after trauma. The disease is self-limiting and usually does not leave residues. We report a case of a 35-year-old man with a post-traumatic osteolysis of the distal clavicle after blunt shoulder trauma. The diagnosis was determined several months after pain persisted in his shoulder. Using this case we discuss the possible pathogenic mechanism, differential diagnosis and treatment options for the post-traumatic osteolysis of the distal clavicle.

Adult↗
PubMed2000

Ca2+-induced Ca2+ release supports the relay mode of activity in thalamocortical cells.

Ca2+ ions play an important role during rhythmic bursting of thalamocortical neurons within sleep. The function of Ca2+ during the tonic relay mode of these neurons during wakefulness is less clear. Here, we report that tonic activity in thalamocortical cells results in an increase in the intracellular Ca2+ concentration and subsequent release of Ca2+ from intracellular stores mediated via ryanodine receptors (RyRs). Blockade of Ca2+ release shifted the regular firing of single action potentials toward the generation of spike clusters. Regular spike firing and intracellular Ca2+ release thus appear to be functionally coupled in a positive feedback manner, thereby supporting the relay mode of thalamocortical cells during wakefulness. Regulatory influences may be coupled to this system via the cyclic ADP ribose pathway.

Action Potentials↗
PubMed2000

Hip dislocation in patients with multiple injuries. A followup investigation.

The combination of traumatic hip dislocation and multiple trauma have not been well documented in the medical literature to date. The role of surgery therefore has not been well defined in these patients. During a 12-year period, 29 consecutive patients with 31 traumatic hip dislocations with concomitant Injury Severity Scores exceeding 18 points were treated at the authors' institution. An initial satisfactory closed reduction was achieved in 23 patients, two patients had failed reductions, and four patients had noncongruous reductions. Open surgical procedures were done on these patients and on 10 additional patients who had associated acetabular or femoral head fractures. Overall, seven patients from the group died including two patients who had surgical procedures. From 17 living patients who did not require surgery for failed or noncongruous reductions, 13 patients were available for followup at a mean of 8 years after their injury. The clinical results at this followup were excellent in three hips, good in seven hips, and fair in four hips. The radiologic results, however, showed that five patients had early (Grades I and II according to Matta) hip degeneration and seven patients had Grade II (according to Ficat) avascular necrosis of the femoral head. These changes were not clinically significant at this followup and it is proposed that these results justify a policy of active treatment of traumatic hip dislocation in patients with multitrauma.

Adolescent↗
PubMed2000

Biochemical changes after trauma and skeletal surgery of the lower extremity: quantification of the operative burden.

OBJECTIVE: To quantify changes in variables of inflammation, coagulation, and fibrinolysis in blunt trauma patients with lower extremity fractures who underwent different types of surgical procedures. DESIGN: Prospective, cohort study. SETTING: Level I university trauma center. PATIENTS: We allocated 83 blunt trauma patients in stable condition and 22 patients eligible for elective hip replacement to four treatment groups. INTERVENTIONS: In 34 multiply traumatized patients with femoral fracture (group PTFF) and in 28 patients with an isolated femoral fracture (group IFF), primary unreamed intramedullary nailing for stabilization of the femoral shaft fracture was performed. In 22 patients, an elective uncemented total hip arthroplasty (group THA) was inserted for osteoarthritis, and in 21 control patients, an isolated ankle fracture (group AF) was acutely stabilized. MEASUREMENTS AND MAIN RESULTS: From serially sampled central venous blood, the perioperative concentrations of interleukin (IL)-6, of tumor necrosis factor-alpha, of prothrombin fragments 1 + 2, and of D-dimer cross-linked fibrin degradation products were evaluated. Intramedullary instrumentation for an isolated femur fracture caused a significant perioperative increase in the concentrations of IL-6 (preoperative IL-6, 52 +/- 12 pg/mL; IL-6 30 mins postinsertion, 78 +/- 14 pg/mL; p = .02). This increase was comparable with group THA (preoperative IL-6, 46 +/- 16 pg/mL; IL-6 30 mins postinsertion, 67 +/- 11 pg/mL; p = .03). A positive correlation occurred between both groups (r = .83, p < .0004). Multiple trauma patients demonstrated significantly (p = .0002) higher IL-6 concentrations than all other groups throughout the study period and showed a significant increase after femoral nailing (preoperative IL-6, 570 +/- 21 pg/mL; IL-6 30 mins postinsertion, 690 +/- 24 pg/mL; p = .003), whereas no perioperative change was seen in group AF. The highest IL-6 increases were associated with a longer ventilation time (group PTFF) and a longer period of positive fluid balances (groups PTFF, IFF, THA). The coagulatory variables demonstrated similar perioperative increases in groups IFF and THA, but not in groups PTFF and AF. The IL-6 concentrations and the prothrombin fragments 1 + 2 concentrations correlated between groups THA and IFF at 30 mins and at 1 hr after surgery (r2 = .64, p < .02). In all patients the clinical variables were stable perioperatively. CONCLUSIONS: Major surgery of the lower extremity causes changes to the inflammatory, fibrinolytic, and coagulatory cascades in patients with stable cardiopulmonary function. The inflammatory response induced by femoral nailing is biochemically comparable to that induced by uncemented total hip arthroplasty. In multiple trauma patients, increases, which occurred in addition to those induced by the initial trauma, were measured. Definitive primary femoral stabilization by intramedullary nailing imposes an additional burden to the patient with blunt trauma. A careful preoperative investigation is required to evaluate whether primary definitive stabilization can be performed safely.

Adult↗
PubMed2000

Pelvic fractures in pregnant multiple trauma patients.

OBJECTIVE: To study the outcome of pelvic fractures and fetuses in pregnant patients involved in blunt multiple trauma. DESIGN: Retrospective follow-up study. SETTING: Level I trauma center. PATIENTS: Pregnant multiple trauma patients with pelvic fractures between 1974 and 1998. INTERVENTIONS: Conservative and operative treatment of pelvic fractures adapted to the clinical status of the mother. MAIN OUTCOME MEASURES: Clinical, functional, and social outcomes were evaluated. RESULTS: Out of 4,196 patients with blunt multiple trauma treated between 1974 and June 1998, seven demonstrated the combination of blunt multiple trauma, pregnancy, and pelvic fractures. These patients had a mean Injury Severity Score of 29.9 points. Five mothers and three fetuses survived their injuries. All dead fetuses died on the scene. One surviving fetus was found to have hydrocephalus unrelated to the injury; the remaining fetuses had an uneventful delivery and were healthy. In two of the three patients whose fetuses survived, the treatment of the pelvic fracture was modified for the sake of fetal well-being. In all of these patients, acceptable outcome was achieved. CONCLUSION: Modification of the treatment of the pelvic fracture in pregnant women with multiple trauma may be necessary to minimize the risk of fetal injury. In our experience with these rare cases, this modified treatment did not severely alter the clinical outcome of the mother's pelvic fracture.

Acetabulum↗
PubMed2000

Appraisal of early evaluation of blunt chest trauma: development of a standardized scoring system for initial clinical decision making.

BACKGROUND: Current techniques for assessment of chest trauma rely on clinical diagnoses or scoring systems. However, there is no generally accepted standard for early judgement of the severity of these injuries, especially in regards to related complications. This drawback may have a significant impact on the management of skeletal injuries, which are frequently associated with chest trauma. However, no convincing conclusions can be determined until standardization of the degrees of chest trauma is achieved. We investigated the role of early clinical and radiologic assessment techniques on outcome in patients with blunt multiple trauma and thoracic injuries and developed a new scoring system for early evaluation of chest trauma. METHODS: A retrospective investigation was performed on the basis of 4,571 blunt polytrauma (Injury Severity Score [ISS] > or = 18) patients admitted to our unit. Inclusion criteria were treatment of thoracic injury that required intensive care therapy, initial Glasgow Coma Scale score greater than 8 points, and no local or systemic infection. Patients with thoracic trauma and multiple associated injuries (ISS > or = 18) were included. In all patients, the association between various parameters of the thoracic injuries and subsequent mortality and morbidity was investigated. RESULTS: A total of 1,495 patients fulfilled the inclusion criteria. Patients' medical records and chest radiographs were reevaluated between May 1, 1998, and June 1, 1999. The association between rib fractures and chest-related death was low (> three ribs unilateral, mortality 17.3%, odds ratio 1.01) unless bilateral involvement was present (> three ribs bilateral, mortality 40.9%, odds ratio 3.43). Injuries to the lung parenchyma, as determined by plain radiography, were associated with chest-related death, especially if the injuries were bilateral or associated with hemopneumothorax (lung contusion unilateral, mortality 25.2%, odds ratio 1.82; lung contusion bilateral + hemopneumothorax, mortality 53.3%, odds ratio 5.1). When plain anteroposterior chest radiographs were used, the diagnostic rate of rib fractures (< or = three ribs) increased slightly, from 77.1% to 97.3% during the first 24 hours of admission. In contrast, pulmonary contusions were often not diagnosed until 24 hours after admission (47.3% at admission, 92.4% at 24 h, p = 0.002). A new composite scoring system (thoracic trauma severity score) was developed that combines several variables: injuries to the chest wall, intrathoracic lesions, injuries involving the pleura, admission PaO2/FIO2 ratio, and patient age. The receiver operating characteristic curve demonstrated an adequate discrimination, as demonstrated by a value of 0.924 for the development set and 0.916 for the validation set. The score was also superior to the ISS (0.881) or the thorax Abbreviated Injury Score (0.693). CONCLUSION: Radiographically determined injuries to the lung parenchyma have a closer association with adverse outcome than chest-wall injuries but are often not diagnosed until 24 hours after injury. Therefore, clinical decision making, such as about the choice of surgery for long bone fractures, may be flawed if this information is used alone. A new thoracic trauma severity score may serve as an additional tool to improve the accuracy of the prediction of thoracic trauma-related complications.

Adolescent↗
PubMed1999

Modulation of the hyperpolarization-activated cation current of rat thalamic relay neurones by intracellular pH.

1. Properties of the hyperpolarization-activated cation current (Ih) were investigated in thalamocortical neurones of an in vitro slice preparation of the rat ventrobasal thalamic complex (VB) before and during changes of pipette pH (pHp), intracellular pH (pHi) and bath pH (pHb) using the whole-cell patch-clamp technique and fluorescence ratio imaging of the pH indicator 2',7'-bis(carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF). 2. Recording of Ih with predefined pHp revealed significant shifts in the voltage dependence of Ih activation (V ) of 4-5 mV to more positive values for a pHp of 7.5 and 2-3 mV to more negative values for a pHp of 6.7 as compared to control values (pHp = 7.1). 3. Application of the weak acid lactate (20 mM), which produced a slow monophasic intracellular acidification, induced a reversible negative shift of V of up to 3 mV. Application of 20 mM TMA, which caused a distinct intracellular alkalinization, shifted V to 4-5 mV more positive values. 4. In slices bathed in Hepes-buffered saline, no significant pHo dependence of Ih was observed. Changing pHo by altering the extracellular [HCO3-] in the presence of constant pCO2 also revealed no significant pHo dependence of Ih. 5. Rhythmic stimulation of thalamocortical neurones with repetitive depolarizing pulse trains caused an intracellular acidification, which reversibly decreased the amplitude and time course of activation of Ih. 6. The results of the present study indicate that shifts in pHi result in a significant modulation of the gating properties of Ih channels in TC neurones. Through this mechanism activity-dependent shifts in pHi may contribute to the up- and downregulation of Ih.

Adenylyl Cyclases↗
PubMed1999

Upregulation of the hyperpolarization-activated cation current in rat thalamic relay neurones by acetazolamide.

1. The effect of inhibition of brain carbonic anhydrase (CA) on the hyperpolarization-activated cation current (Ih) of thalamocortical (TC) neurones of the rat ventrobasal thalamic complex (VB) was investigated in an in vitro slice preparation using the whole-cell patch-clamp technique and fluorescence ratio imaging of the pH indicator 2',7'-bis(carboxyethyl)-5(and -6)-carboxyfluorescein (BCECF). 2. Recording of Ih before and after addition of 0.4-0.8 mM acetazolamide to the bathing fluid revealed a significant shift in the voltage dependence of activation (V ) of 5-7 mV to more positive potentials. 3. Simultaneous recording of Ih and BCECF fluorescence ratio (F420/F495) revealed an increase in Ih amplitude accompanied by an intracellular alkalinization upon application of acetazolamide. The CA inhibitor ethoxyzolamide (EZA, 50 microM) also led to an intracellular alkalinization and a subsequent 4-5 mV positive shift of V of Ih. 4. Acetazolamide and EZA both profoundly slowed the rapid fall of pHi upon switching from Hepes- to CO2/HCO3--buffered superfusate, indicating intracellular CA isoforms in TC neurones. 5. In slices bathed in Hepes-buffered saline, addition of acetazolamide had no effect on the amplitude and time course of activation of Ih, indicating that the action of acetazolamide on Ih was dependent on the presence of HCO3-. 6. Under current-clamp conditions, the neuronal response to hyperpolarizing current pulses in the presence of acetazolamide was decreased as compared to control. This resulted in a strongly reduced ability of TC neurones to produce rebound Ca2+-mediated spikes. 7. The present results implied that in TC neurones acetazolamide led to an intracellular alkalinization which causes, due to its pH sensitivity, an increase in Ih.

Acetazolamide↗
PubMed1999

Direct synaptic connections of axons from superior colliculus with identified thalamo-amygdaloid projection neurons in the rat: possible substrates of a subcortical visual pathway to the amygdala.

The aim of the present study was to identify synaptic contacts from axons originating in the superior colliculus with thalamic neurons projecting to the lateral nucleus of the amygdala. Axons from the superior colliculus were traced with the anterograde tracers Phaseolus vulgaris leucoagglutinin or the biotinylated and fluorescent dextran amine "Miniruby." Thalamo-amygdaloid projection neurons were identified with the retrograde tracer Fluoro-Gold. Injections of Fluoro-Gold into the lateral nucleus of the amygdala labeled neurons in nuclei of the posterior thalamus which surround the medial geniculate body, viz. the suprageniculate nucleus, the medial division of the medial geniculate body, the posterior intralaminar nucleus, and the peripeduncular nucleus. Anterogradely labeled axons from the superior colliculus terminated in the same regions of the thalamus. Tecto-thalamic axons originating from superficial collicular layers were found predominantly in the suprageniculate nucleus, whereas axons from deep collicular layers were detected in equal density in all thalamic nuclei surrounding the medial geniculate body. Double-labeling experiments revealed an overlap of projection areas in the above-mentioned thalamic nuclei. Electron microscopy of areas of overlap confirmed synaptic contacts of anterogradely labeled presynaptic profiles originating in the superficial layers of the superior colliculus with retrogradely labeled postsynaptic profiles of thalamo-amygdaloid projection neurons. These connections may represent a subcortical pathway for visual information transfer to the amygdala.

Amygdala↗
PubMed1999

Reticuloendothelial system activity and organ failure in patients with multiple injuries.

HYPOTHESIS: Reticuloendothelial system function is altered in patients with multiple trauma and organ failure. DESIGN: Prospective cohort study. SETTING: Surgical intensive care unit at a level I trauma center. PATIENTS: Patients with multiple blunt trauma and injury severity scores greater than 20, with no referrals. INTERVENTIONS: Every second day reticuloendothelial system (RES) clearance capacity and liver blood flow were determined by administering labeled human albumin. Liver function was measured by enzymatic decay of indocyanine green, and levels of plasma tumor necrosis factor alpha were evaluated. RESULTS: In nonsurviving patients with blunt trauma, RES function was altered and was associated with organ dysfunction and infectious complications. Of 61 patients, 42 survived and 19 did not. Sixteen patients (84%) died of multiple organ failure. Significantly elevated RES activity (colloid clearance rate) was present between day 5 and day 13 after trauma in nonsurvivors (0.86+/-0.16 [mean +/- SD] on day 7, P = .003) compared with survivors (0.48+/-0.08 on day 7) and 20 healthy volunteers (0.47+/-0.06); RES activity then decreased to subnormal levels in nonsurvivors. Tumor necrosis factor alpha plasma levels were elevated early after injury only in nonsurvivors (on day 1: nonsurvivors, 1.2+/-0.4 ng/mL [mean +/- SD]; survivors, 0.5+/-0.2 ng/mL; P = .02). Indocyanine green half-life values increased late after trauma, indicating late organ failure (on day 19: nonsurvivors, 111+/-29 minutes [mean +/- SD]; survivors, 12+/-4 minutes; P<.001). CONCLUSIONS: Early after trauma, nonsurviving patients demonstrated increased proinflammatory cytokine levels, followed by a state of pathological hyperactivation of the reticuloendothelial system prior to death. These results indicate that the stationary host defense system is involved in the mechanisms causing organ failure after severe trauma.

Adult↗
PubMed1999

[Extracorporeal shock wave therapy for delayed union of long bone fractures - preliminary results of a prospective cohort study].

Extracorporal shock wave therapy (ESWT) has been postulated as an additional therapeutic option in nonunion after fracture treatment. We have reexamined patients with nonunions treated at our institution to evaluate the efficacy of the method. In a prospective nonrandomized study patients were investigated with a minimum duration of nonunion of 6 months. Following 2 cycles of ESWT with 2000 impulses/18 kV, the reevaluation was performed at 1, 3 and 6 months after treatment. A total of 27 pseudarthroses was reevaluated, in 11 one or more reosteosyntheses had been performed prior to ESWT. Following ESWT we found a success rate of 41 % (n = 11). The clinical evidence of subjective, clinical improvement was found in 5 of these patients within 1 month, in all of these patients within a period of 3 months. Radiologic evidence of improvement occurred in none of these patients within 1 month, in all of these patients within 6 months. ESWT appears to represent an additional treatment option in patients with longstanding nonunion. If no improvement occurs, the maximum delay of reosteosynthesis is three months.

Adolescent↗