[Spinal epidural abscess as a complication of a finger infection]. / Een spinaal epiduraal abces als complicatie van een ontstoken vinger.

An 81-year-old man was treated with intravenous antibiotics for a soft tissue infection in a finger. Despite adequate antibiotic treatment, he developed signs of spinal cord injury caused by a cervical spinal epidural abscess. An emergency laminectomy was performed. The neurological impairment appeared to be irreversible, and the patient died. Spinal epidural abscess is a rare and serious complication ofa bacteraemia. It is often caused by an infection of the skin or soft tissue with Staphylococcus aureus. Given the risk of rapidly progressive and irreversible neurological damage, this complication must be treated as soon as possible. The treatment of choice is surgery. Conservative management with intravenous antibiotics is an option only under strict conditions.

Brain tissue oxygen response in severe traumatic brain injury.

OBJECTIVE: To investigate clinical relevance and prognostic value of brain tissue oxygen response (TOR: response of brain tissue pO(2) to changes in arterial pO(2)) in traumatic brain injury (TBI). PATIENTS AND METHODS: In a prospective cohort study TOR was investigated in 41 patients with severe TBI (Glasgow Coma Score < or =8) in whom continuous monitoring of brain tissue oxygen pressure (PbrO(2)) was performed.TOR was investigated each day over a five day period for 15 minutes by increasing FiO(2) on the ventilator setting. FiO(2) was increased directly from baseline to 1.0 for a period of 15 minutes under stable conditions (145 tests). In 34 patients the effect of decreasing PaCO(2) was evaluated on TOR by performing the same test after increasing inspiratory minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO(2) was performed in all patients. Outcome at six months was evaluated according to the Glasgow Outcome Scale. For statistical analysis the Mann-whitney U-test was used for ordinally distributed variables, and the Chi-square test for categorical variables. Predictive value of TOR was analyzed in a multivariable model. RESULTS: 145 tests were available for analysis. Baseline PbrO(2) varied from 4.0 to 50 mmHg at PaO(2) values of 73-237 mmHg. At FiO(2) settings of 1.0, PbrO(2) varied from 9.1-200 mmHg and PaO(2) from 196-499 mmHg. Three distinct patterns of response were noted: response type A is characterized by a sharp increase in PbrO(2), reaching a plateau within several minutes; type B by the absence of a plateau, and type C by a short plateau phase followed by a subsequent further increase in PbrO(2). Patterns characterized by a stable plateau (type A), considered indicative of intact regulatory mechanisms, were seen more frequently from 48 hours after injury on. If present within the first 24 hours after injury such a response was related to more favorable outcome (p = 0.06). Mean TOR of all tests was 0.73 +/- 0.59 with an median TOR of 0.58. Patients with an unfavourable outcome had a higher TOR (1.03 +/- 0.60) during the first 24 hours, compared to patients with a favorable outcome (0.61 +/- 0.51; p = 0.02). Multiple logistic regression analysis supported the independent predictive value of tissue oxygen response for unfavorable outcome (odds ratio 4.8). During increased hyperventilation, mean TOR decreased substantially from 0.75 +/- 0.54 to 0.65 +/- 0.45 (p = 0.06; Wilcoxon test). Within the first 24 hours after injury a decrease in TOR following hyperventilation was significantly related to poorer outcome (p = 0.01). CONCLUSIONS: Evaluation of TOR affords insight in (disturbances in) oxygen regulation after traumatic brain injury, is of prognostic value and may aid in identifying patients at (increased) risk for ischemia.

CO2 reactivity and brain oxygen pressure monitoring in severe head injury.

OBJECTIVE: To investigate the effect of hyperventilation on cerebral oxygenation after severe head injury. DESIGN: A prospective, observational study. SETTING: Neurointensive care unit at a university hospital. PATIENTS: A total of 90 patients with severe head injury (Glasgow Coma Scale score < or =8), in whom continuous monitoring of brain tissue oxygen pressure (PbrO2) was performed as a measure of cerebral oxygenation. INTERVENTIONS: Arterial PCO2 was decreased each day over a 5-day period for 15 mins by increasing minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO2, was performed in all patients. Absolute and relative PbrO2/PaCO2 reactivity was calculated. Outcome at 6 months was evaluated according to the Glasgow Outcome Scale. MEASUREMENTS AND MAIN RESULTS: Effective hyperventilation, defined by a decrease of PaCO2 > or =2 torr (0.27 kPa), was obtained in 218 (84%) of 272 tests performed. Baseline PaCO2 averaged 32.3 +/- 4.5 torr (4.31 +/- 0.60 kPa). Average reduction in PaCO2 was 3.8 +/- 1.7 torr (0.51 +/- 0.23 kPa). PbrO2 decreased by 2.8 +/- 3.7 torr (0.37 +/- 0.49 kPa; p < .001) from a baseline value of 26.5 +/- 11.6 torr (3.53 +/- 1.55 kPa). PbrO2/PaCO2 reactivity was low on day 1 (0.8 +/- 2.3 torr [0.11 +/- 0.31 kPa]), increasing on subsequent days to 6.1 +/- 4.4 torr (0.81 +/- 0.59 kPa) on day 5. PbrO2/PaCO2 reactivity on days 1 and 2 was not related to outcome. In later phases in patients with unfavorable outcome, relative reactivity was increased more markedly, reaching statistical significance on day 5. CONCLUSIONS: Increased hyperventilation causes a significant reduction in PbrO2, providing further evidence for possible increased risk of secondary ischemic damage during hyperventilation. The low PbrO2/PaCO2 reactivity on day 1 indicates the decreased responsiveness of cerebral microvascular vessels to PaCO2 changes, caused by generalized vascular narrowing. The increasing PbrO2/PaCO2 reactivity from days 2 to 5 suggests that the risk of compromising cerebral oxygenation by hyperventilation may increase over time.

Brain oxygen tension in severe head injury.

OBJECTIVE: Ensuring adequate cerebral oxygenation and perfusion is of fundamental importance in the treatment of patients with acute cerebral disorders. Online continuous monitoring of brain oxygenation is possible with a parenchymal microelectrode that measures local brain oxygen tension. The ultimate question is whether therapeutic approaches can be targeted on the basis of such monitoring. Before this question can be addressed, the technique requires validation in the clinical setting. The frequency of occurrence of low values and its relation to outcome need to be established. METHODS: One hundred one comatose head-injured patients (Glasgow Coma Scale score < or = 8) were studied. Local brain oxygen tension probes were inserted in an undamaged part of the frontal region. Patients were treated in conformance with the European Brain Injury Consortium guidelines. Outcome at 6 months was determined by Glasgow Outcome Scale score. RESULTS: Early brain tissue hypoxia was frequently observed, despite aggressive treatment for intracranial pressure and cerebral perfusion pressure. Values lower than 15 mm Hg, for a duration longer than 30 minutes, were observed in 57 patients. Values lower than 10 mm Hg in 42 patients, and lower than 5 mm Hg in 22 patients, were observed during the first 24 hours. Depth and duration of tissue hypoxia were related to outcome and proved to be an independent predictor of unfavorable outcome and death. CONCLUSION: Monitoring the partial oxygen pressure of local brain tissue is a safe and reliable method for regulating cerebral oxygenation. Because brain tissue hypoxia occurs frequently and is significantly related to poor outcome, future efforts should be aimed at the treatment of brain tissue hypoxia. The effects of such brain hypoxia-targeted treatment need to be established in a multicenter study.

A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: discovery of a potential atypical antipsychotic agent.

As part of a program to develop dopamine D4 antagonists for the treatment of schizophrenia, we discovered a series of 6- and 7-(phenylpiperazinyl)- and -(phenylpiperidinyl)methylbenzoxazinones through mass screening of our compound library. A structure-activity relationship SAR study was carried out involving substituents on the phenyl ring, and several selective D4 antagonists were identified. The 7-substituted benzoxazinones showed more activity in neurochemical and behavioral tests than the 6-substituted series. One of the most potent and selective compounds (26) was found to have potent activity in animal tests predictive of antipsychotic activity in humans after oral administration. This paper describes the SAR of the benzoxazinone series and the preclinical characterization of 26.

The prognostic importance of the volume of traumatic epidural and subdural haematomas revisited.

The size of a traumatic intracranial haematoma at the moment of diagnosis can be impressive. Haematoma thickness is an inaccurate estimator of haematoma volume, and association with patient outcome is controversial. In this study computerized volumetry of offline digitized CT scans was used to relate haematoma volume with both patient characteristics on admission and at the six months outcome. This retrospective study covered the time period 1981/1990. Ninety eight patients operated upon for an epidural haematoma and 91 patients operated upon for an acute subdural haematoma were analyzed. The relative importance of clinical data, CT scan parameters, and calculated haematoma volumes was determined by multivariate analysis. Volume of the haematoma did not correlate with preoperative neurological condition or the six months outcome in either group, and consequently is not of additional prognostic value.

Brain parenchyma/pO2 catheter interface: a histopathological study in the rat.

Local cerebral oxygenation can be monitored continuously using an intraparenchymal Clark-type pO2 sensitive catheter. Measured values of brain tissue pO2 (PbrO2) not only depend on the clinically interesting balance between oxygen offer and demand, but also on catheter properties and characteristics of the probe tissue interface. Microdamage surrounding pO2-sensitive needles, inserted into various tissues, has been reported; we evaluated histologic changes at the probe tissue interface after insertion of pO2 probes, suitable for clinical use, in the rat brain. The effect of insertion of the probe itself (mechanical damage), the application of micropotential during the measurements, and the effect of time was evaluated using digital image analysis of H&E-stained histological slices. Surrounding the probe tract, a zone of edema with an average radius of 126.8 microm was seen; microhemorrhages with an average surface area of 56.2 x 10(3) microm2 were observed in nearly all cases. The area of edema and the presence of microhemorrhages were not influenced by performed measurements or by time. Intraventricular blood was observed in 10 of 19 rats studied. Measured low PbrO2 values were related to the presence of a microhemorrhage in either probe tract or ventricles. Tissue damage due to the measurements is negligible, and the amount of edema itself does not influence the accuracy or response time of the pO2 probe. Low PbrO2 readings, however, could be caused by local microhemorrhages, undetectable on CT or MRI.

Monitoring brain oxygen tension in severe head injury: the Rotterdam experience.

Cerebral ischemia is considered the central mechanism leading to secondary brain damage in patients with severe head injury. We investigated the technique of continuous monitoring of local brain tissue oxygen tension as parameter for cerebral oxygenation. Eighty-two patients with non penetrating severe head injury were studied. No complications of the monitoring technique were seen. Postmeasurement calibration of the catheters showed a very low zero drift and acceptable sensitivity drift. Low PbrO2 values were seen within the first 12 to 24 hours of injury. Early occurrence of values below 10 mm Hg indicated a poor prognosis. Comparative measurements between two catheters performed in six patients showed differences in absolute values measured, but a good correlation of relative changes was observed. We conclude that continuous monitoring of PbrO2 is reliable, clinically applicable and provides the clinician with a better insight in cerebral oxygenation and hopefully should help in targeting therapy towards improved cerebral oxygenation.

Isoindolinone enantiomers having affinity for the dopamine D4 receptor.

PD 108635 (1) was identified as a potent dopamine D4 ligand and we wanted to replace the benzylic alcohol with a metabolically more stable moiety. Investigations led to the discovery of a series of isoindolinones having D4 affinity.

Signet-ring cell oligodendroglioma--report of two cases and discussion of the differential diagnosis.

Two cases of oligodendroglioma consisting largely of signet-ring cells were analyzed histopathologically, immunohistochemically and at the ultrastructural level. The signet-ring cells were negative for a panel of tumor lineage markers including glial fibrillary acidic protein, and were negative for Ki-67 (MIB-1 immunohistochemistry). In contrast with the abundance of lysosomal structures reportedly present in the so-called eosinophilic granular cells in oligodendrogliomas, degenerating mitochondria were mainly seen in the cytoplasm of the signet-ring cells. The differential diagnosis of the oligodendroglial signet-ring cell tumors occurring in children and in adults is discussed.

Sagittal sinus occlusion, caused by an overlying depressed cranial fracture, presenting with late signs and symptoms of intracranial hypertension: case report.

A case of delayed signs of intracranial hypertension after open depressed cranial fracture occluding the superior sagittal sinus is reported. Elevating depressed fractures overlying a cranial venous sinus is hazardous. Conservative management of the intracranial hypertension, including repeated lumbar punctures, led to an unimpaired outcome. The options of management of delayed problems caused by traumatic venous occlusion are discussed.

Herniation of the lung following video-assisted minithoracotomy.

Intercostal pulmonary hernia is a rare finding in surgical practice. The hernia presents as an elastic expansion on the outer surface of the chest wall that is usually easily reducible. The protrusion increases in size during expiration and decreases, or disappears, during inspiration. Usually there are no other symptoms. We describe a man who developed a thoracic herniation of the lung 2 1/2 months after a video-assisted minithoracotomy. A concise review of the literature is included.

Failure of the gamma nail in a highly unstable proximal femur fracture: report of four cases encountered in The Netherlands.

Static forces of body weight and dynamic forces induced by walking are a challenge toward lasting fixation devices in the case of unstable peritrochanteric fractures. Experiences with the newly developed gamma nail internal fixation technique are promising. The fixation is stable, complication rates are low, and fractures of the gamma nail itself have not been reported before. From the Dutch experience, the authors describe the four known cases of implant failure. In cases in which the process of bony healing is disturbed, the dynamic stresses during ambulation become large enough to cause metal fatigue fractures. In these cases adjuvant and appropriate measures should be undertaken.

Quantitative analysis of blood-brain barrier damage in two models of experimental head injury in the rat.

The integrity of the blood-brain barrier was studied in a new model of closed head injury, and in an established model of fluid percussion injury, in the rat. Brain injury in this new model is induced by impact and acceleration of the protected rat skull. Severe hypertension is not a characteristic of this new model as compared to the tremendous surge following direct dural percussion. This is important because of the well known sensitivity of the cerebral microvasculature for acute hypertension. Using a radioactive tracer technique the dysfunction of the barrier was quantified. It is shown that the BBB is temporarily damaged due to trauma, subsequent arterial pressure surge, as seen in the percussed animals, deteriorates the dysfunction of the barrier even further. This study indicates that vascular damage is a key event following head injury. Yet the concomitant basic pathophysiological sequelae of different models must be considered when studying barrier damage and cerebral edema following brain injury. Time window studies of the barrier indicate that the barrier seals within a few hours following severe concussive head injury, and in the absence of a hypertensive surge.

Signal detection in temporally modulated and spectrally shaped maskers.

The first part of this paper presents several experiments on signal detection in temporally modulated noise, yielding a general approach toward the concept of comodulation masking release (CMR). Measurements were made on masked thresholds of both long- and short-duration, narrow-band signals presented in a 100% sinusoidally amplitude-modulated (SAM) noise masker (modulation frequency 32 Hz), as a function of masker bandwidth from 1/3 oct up to 13/3 octs, while the masker band was geometrically centered at signal frequency. With the short-duration signals placed in the valley of the masker, a substantial CMR (i.e., a decrease of masked threshold with increasing masker bandwidth) was found, whereas for the long-duration signals CMR was smaller. Furthermore, investigations were carried out to determine whether CMR changes when the bandwidth of the signals, consisting of bandpass impulse responses, is increased. The data indicate that substantial CMR remains even when all masker bands contain a signal component, thus minimizing across-channel differences. This finding is not in line with current models accounting for the CMR phenomenon. The second part of this paper concerns signal detection in spectrally shaped noise. Also investigated was whether release from masking occurs for the detection of a pure-tone signal at a valley or a peak of a simultaneously presented masking noise with a sinusoidally rippled power spectrum, when this masker was preceded and followed by a second noise (temporal flanking burst) with an identical spectral shape as the on-signal noise. Similar to CMR effects for temporal modulations, the data indicate that coshaping masking release (CSMR) occurs when the signal is placed in a valley of the spectral envelope of the masker, whereas no release from masking is found when the signal is placed at a peak of the spectral envelope of the masker. The implications of these experiments for measures of spectral and temporal resolution are discussed.

Spectro-temporal integration in signal detection.

This paper is concerned with aspects of temporal integration and across-frequency integration in signal detection. Previous experiments on the detection of brief broadband signals (clicks) in continuous broadband noise revealed efficient spectral integration. The extent to which this effect is restricted to a critical time window was investigated by manipulating the temporal relations among the signal components in different frequency regions. In a typical experiment, the signal consists of nine brief Gaussian-shaped tone pulses, equally distributed at 1/3-oct intervals, each with a spectral width of about 1/3 oct, and each equally detectable in white noise. In the synchronized condition (i.e. coinciding peaks of the nine Gaussian envelopes), the detection threshold is reached when the levels of the nine individual tone pulses are about 8 dB below their individual threshold levels (efficient spectral integration). When the signal is progressively desynchronized (i.e. noncoinciding peaks of the Gaussian envelopes), detection threshold is found to increase. This suggests that efficient spectral integration in signal detection is confined to a narrow time window, with a typical value of 30 ms. Similar experiments were performed with respect to the efficiency of temporal integration. For constant-duration signals (100 ms), the detection threshold is found to increase when progressively widening signal bandwidth. The data indicate that the efficient temporal integration in signal detection is confined to a narrow frequency window, which, not surprisingly, corresponds to the critical bandwidth.

Efficient across-frequency integration in short-signal detection.

A series of experiments was performed on the influence of bandwidth on the masked threshold of brief deterministic signals in continuous broadband noise. The signal bandwidth is quantified by the number (n) of constituent 1/3-oct bands. For n increasing from 1 to typically 9, the masked-threshold level in the constituent 1/3-oct bands is found to decrease by 8 log(n). This integration rule is obtained when each of the 1/3-oct bands covered by the signal equally contributes to detection, i.e., that, for each of these 1/3-oct bands, the difference between signal level and the individual masked-threshold level is the same. It was found that this integration rule also applies to noncontiguous signal spectra and that it remains intact over a broad range of masker levels. Commonly, the masked threshold of compound signals (for instance, n frequency components with a spacing of typically 1/3 oct), relative to the masked threshold of single-component signals, has been described by a 5 log(n) integration rule. However, this rule was obtained for signal durations of typically 100 ms or more. For the present brief signals (typically 10 ms or less), the across-frequency integration is found to be more effective.