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Biomedical subjects

G J Bouma

Publications and source records attributed to G J Bouma.

At least 19 recordsLinked to original sources
PubMed2005

[Headache and impaired consciousness due to the spontaneous intracranial hypotension syndrome].

A 51-year-old man presented with a 6-week history of progressive headache, confusion and ataxic gate. The symptoms were not preceded by trauma or lumbar puncture. A CT-scan of the brain revealed bilateral subdural fluid accumulation and hyperdensities in the subarachnoid space. In view of the signs of a subarachnoid haemorrhage, angiography was performed but showed no indications of an aneurysm. An MRI-scan of the head revealed abnormalities in line with intracranial hypotension. CT-myelography of the whole spine revealed a cerebrospinal fluid leak at the level of the fifth and sixth thoracic vertebrae. The patient recovered completely after placement of an epidural blood patch at this level. Spontaneous intracranial hypotension shows clinical similarities with the symptoms following a lumbar puncture. In most cases it can be treated by conservative measures. However, invasive measures are sometimes necessary to close the defect in the meninges.

Brain↗
PubMed2003

Expression of CD80 on Kupffer cells is enhanced in cadaveric liver transplants.

In experimental animals inhibition of T cell co-stimulation immediately after organ transplantation effectively prevents rejection. We investigated whether the expression of co-stimulatory molecules is enhanced in cadaveric liver transplants, whether their expression is influenced by the transplantation procedure, and whether variation in expression between liver transplants is related to the occurrence of acute rejection. Expression of CD80, CD86 and the macrophage marker CD68 were determined by immunohistochemistry in biopsies from 40 clinical liver transplants obtained at different time-points during the transplantation procedure, and in normal liver tissue obtained from 10 human livers. Expression of CD80 and CD86 on Kupffer cells was graded by comparison with CD68-staining. In a subgroup CD80 and CD86 mRNA was quantified by real-time detection polymerase chain reaction. CD86 was expressed in all liver transplants and normal livers on the majority of Kupffer cells. CD80 was absent or sporadically expressed in normal liver tissue, but in 18 of 40 liver transplants at least one-quarter of Kupffer cells expressed CD80. CD80- and CD86-mRNA and protein expression in liver transplants did not change during the warm ischaemic and reperfusion phases of the transplantation procedure. CD80-expression on Kupffer cells varied strongly between individual donor livers; this variation was, however, not significantly related to the occurrence of acute rejection after transplantation. In conclusion, in nearly half of cold-preserved cadaveric liver transplants an increased proportion of Kupffer cells express CD80 at the time of transplantation in comparison with normal liver tissue. The expression was not further induced by warm ischaemia and reperfusion. However, the observed variation in CD80-expression between liver transplants is not a accurate predictive measure for acute rejection.

Adult↗
PubMed2002

Intraoperative monitoring of brain tissue oxygen and carbon dioxide pressure in peritumoural oedema by stereotactic placement of multiparameter microsensors.

Ischaemia may play an important role in peritumoural brain oedema and swelling, but little data exist so far on brain tissue oxygenation adjacent to a tumour mass. We have monitored brain tissue oxygen tension (ptiO2) and brain tissue CO2 tension (ptiCO2) in 19 patients undergoing craniotomy for resection of a brain tumour using a multiparameter sensor placed in the brain parenchyma. Accurate placement of this probe in the peritumoural area was accomplished with the aid of a 3-D neuronavigation system. Due to various problems we obtained useful data in only 13/19 patients. The presence of brain swelling was associated with a significant rise in ptiO2 upon opening of the dura from 7.1 +/- 7.8 to 23.6 +/- 14.7 mm Hg. The average ptiO2 before tumour resection was 18.1 +/- 10.8 mm Hg. A significant improvement in ptiO2 occurred after tumour resection to an average ptiO2 of 29.7 +/- 15.2 mm Hg. From these preliminary data, we conclude that ptiO2 is depressed in the peritumoural area, and improves following tumour resection. Stereotactic placement of sensors for intraoperative ptiO2 monitoring is feasible and may enhance data quality. Nevertheless, the high incidence of failures with this type of sensor remains a matter of concern.

Adult↗
PubMed2001

Abnormal microcirculation in brain tumours during surgery.

Orthogonal Polarisation Spectral imaging is a new clinical technique that uses polarised light to visualise the microcirculation of organ surfaces. We have used this technique to compare the functional microcirculatory properties of three types of brain tumour with those of the normal cortex. Meningiomas were characterised by chaotic and dilated vessels with almost no erythrocyte movement and a dark background, glioblastoma by few vessels with low flow and a background close to that of the healthy cortex, and metastases by a very dark background, almost no flow, and a chaotic vascular pattern. This technique could provide useful information about microcirculatory morphology and kinetics for diagnostic use during neurosurgery.

Brain Neoplasms↗
PubMed2001

In vitro cytokine production of TNFalpha and IL-13 correlates with acute liver transplant rejection.

Individuals may differ in their capacity to produce cytokines. Since cytokines play a key role in allograft rejection, we investigated whether inter-individual differences in cytokine production by in vitro stimulated PBMC are related to the occurrence of acute liver transplant rejection. Our study group comprised 49 liver transplant recipients and 30 healthy individuals. Rejection, which occurred within one month after liver transplantation, was defined in 22 patients ("rejectors") as biopsy-proven rejection, treated with high dose prednisolone. Patients who never experienced rejection episodes were termed as "nonrejectors" (n=27). PBMC of healthy individuals and of liver transplant recipients, collected late after transplantation (mean 3.5 years), were cultured in the presence and absence of Concanavalin A. The production of TNF-alpha, IFN-gamma, IL-10, and IL-13 was measured in supernatant after 1, 2, 3, 4, and 7 days of cell culture. In cell culture, stimulated PBMC of rejectors were found to produce significantly higher levels of TNF-alpha, while there was a trend towards higher production of IFN-gamma and IL-10 as compared to nonrejectors. After grouping patients into high or low cytokine producers based upon reference levels of the healthy individuals using multivariate analysis it was found that occurrence of acute liver transplant rejection correlated to high production of TNF-alpha and low production of IL-13. After stimulated cell culture PBMC of liver transplant recipients show a differential production of TNF-alpha and IL-13 which is correlated with the occurrence of acute liver transplant rejection.

Acute Disease↗
PubMed1999

Comparison of two types of surgery for thoraco-lumbar burst fractures: combined anterior and posterior stabilisation vs. posterior instrumentation only.

This retrospective study compares clinical outcome following two different types of surgery for thoracolumbar burst fractures. Forty-six patients with thoracolumbar burst fractures causing encroachment of the spinal canal greater than 50% were operated on within 30 days performing either: combined anterior decompression and stabilisation and posterior stabilisation (Group 1) or posterior distraction and stabilisation using pedicle instrumentation (AO internal fixator) (Group 2). We evaluated: neurological status (Frankel Grade), spinal deformities, residual pain, and complications. The average follow-up was 6 years. There were no significant differences between the patients in both groups concerning age, sex, cause of injury and the presence of other severe injuries. Neurological dysfunction was present in 39% of all cases. Bony union occurred in all patients. Loss of reduction greater than 5 degrees and instrumentation failure occurred significantly more often in Group 2 compared to Group 1, but the kyphosis angle at late follow-up did not differ between groups, due to some degree of overcorrection initially after surgery in Group 2. The clinical outcome was similar in both groups, and all but one patient with neurological deficits improved by at least one Frankel grade. Indirect decompression of the spinal canal by posterior distraction and short-segment stabilisation with AO internal fixator is considered appropriate treatment for the majority of unstable thoracolumbar burst fractures. This is a less extensive surgical procedure than a combined anterior and posterior approach.

Adult↗
PubMed1999

Human bone allografts can induce T cells with high affinity for donor antigens.

We analysed the cellular immune response in ten transplantations of different massive bone allografts, of which five had a poor clinical outcome. Cytotoxic T lymphocytes (CTL) and T helper lymphocytes (TH) against mismatched donor antigens were found in all patients. More importantly, CTL with a high affinity for donor antigens were found in five cases. High-affinity CTL need no CD8 molecule to stabilise the antigen binding and are strongly associated with rejection of heart and corneal transplants. Even after removal of most of the bone-marrow cells, we found high-affinity CTL and high TH frequencies. This T-cell response could be detected over a period of years. We conclude that frozen bone allografts can induce high-affinity donor-specific CTL. The present assay allows qualification and quantification of the levels of CTL and TH in the blood. This approach may be helpful in studying the effect of the immune response on the outcome of the graft.

Adolescent↗
PubMed1998

Pathogenesis of traumatic brain swelling: role of cerebral blood volume.

The pathogenesis of traumatic brain swelling is unclear. Brain edema (increased water content) is considered an important cause of swelling, but there is also evidence that vasodilatation with increased cerebral blood volume (CBV) plays a role. We have evaluated early posttraumatic changes in CBV in 37 head-injured patients, using dynamic contrast-enhanced computerized tomography (CT) in combination with stable Xenon-enhanced CT for measurement of cerebral blood flow (CBF). This technique enables rapid determination of CBV without interfering with patient care. CBV values ranged from 2.0 to 10.1 ml/100 g. There was no relationship the time after injury at which the measurements were taken. CBV did not correlate with CBF in the early posttraumatic period. Patients with raised ICP (> 20 mm Hg) had significantly higher CBV that patients with normal ICP (5.4 +/- 2.1 vs 3.7 +/- 0.9 ml/100 g). Yet, the presence of signs of brain swelling on CT had no relation to the level of CBV. These data suggest that increased CBV may contribute to raised ICP, but that brain swelling is not caused by increased CBV alone, and is more likely accounted for by brain edema. We speculate that cerebral energy failure is the unifying cause of both intracellular edema and cerebral vasodilation leading to swelling of brain tissue.

Adolescent↗
PubMed1996

In vitro sensitivity to prednisolone may predict kidney rejection after steroid withdrawal.

A maintenance immunosuppressive regimen of cyclosporine and steroids after renal transplantation has proven to be a successful policy to obtain long-term graft survival. However, serious side-effects are associated with this therapy; these include an increased risk for infections, cancer, and cardiovascular morbidity and mortality. Therefore, this pilot study was conducted to investigate the possibility of reducing the immunosuppressive load after transplantation. To this end, we tried to develop an in vitro assay to predict graft rejection after withdrawing steroids from the immunosuppressive therapy. Patients who had stable renal function at least one year after transplantation were randomly divided into a group that continued to receive standard immunosuppression of cyclosporine and steroids and a group to be withdrawn from steroid therapy, the latter group being the subject of the present study. Patients withdrawn from steroids were monitored closely and when a biopsy-proven rejection occurred, steroid treatment was reestablished. Blood was collected from patients preceding steroid withdrawal and at fixed time points thereafter. In case of suspected rejection, blood was also taken before biopsy, before steroid treatment was reestablished. In the in vitro limiting dilution analysis-assays cytotoxic T lymphocyte precursor frequencies directed against kidney donor HLA-antigens were determined, in the absence or presence of cyclosporine and several concentrations of prednisolone and the combination of these agents. Confirming earlier results, we found that the number of cyclosporine-resistant cytotoxic T lymphocytes increased prior to a rejection crisis, while they did not change or even decreased in patients who retained normal graft function after steroid withdrawal. More importantly, the results show that 10(-7) M prednisolone in vitro differentially affected donor-specific cytotoxic T lymphocyte precursor frequencies in patients who experienced a rejection crisis after steroid withdrawal, compared with those who remained to do well. This heterogeneity could be detected before the start of steroid withdrawal. Therefore, we conclude that the present data justify a prospective clinical trial to investigate the possible application of this in vitro assay to predict for which patients steroid withdrawal might be considered.

Adult↗
PubMed1996

Pregnancy can induce priming of cytotoxic T lymphocytes specific for paternal HLA antigens that is associated with antibody formation.

Some transplant centers consider paternal HLA antigens as unacceptable mismatches for mothers awaiting kidney transplantation. It is feared that a pregnancy may cause priming of the maternal immune response directed toward paternal HLA antigens. Should a woman receive an organ from a donor who shares those paternal HLA antigens, the risk of graft rejection might be increased. It is known that some women, as a consequence of pregnancy, develop antibodies specific for paternal HLA antigens. The purpose of the present study was to investigate whether a pregnancy can also prime the cellular immune response and whether this occurs in all cases. Frequencies of maternal cytotoxic T lymphocytes directed to paternal HLA antigens were evaluated in limiting dilution analysis assays and compared with those directed to third-party HLA antigens. Differentiation between naive and in vivo primed cytotoxic T lymphocytes was made by performing these assays in the absence and presence of anti-CD8, respectively. No difference in the frequency nor sensitivity to blocking by anti-CD8 was found when maternal cytotoxic T lymphocytes directed toward paternal HLA antigens were compared with those against third-party HLA antigens. However, more heterogeneous responses were detected against paternal HLA antigens. Therefore, paternal antigens that had been inherited by children were analyzed separately from the paternal antigens that had not been inherited. Furthermore, the presence of pregnancy-induced HLA antibodies was taken into consideration. Naive cytotoxic T lymphocyte responses were detected against paternal antigens that had never been inherited and those that had been inherited but had not induced antibody formation. In contrast, inherited paternal antigens that had induced HLA-specific antibodies in the mother gave rise to elevated cytotoxic T lymphocyte precursor frequencies, as compared with the response to third-party antigens. Also, the cytotoxic T lymphocytes were found to be more resistant to inhibition by anti-CD8, suggesting that these cells had been primed in vivo. These results suggest that not all paternal HLA antigens have to be considered as unacceptable mismatches. Only those individuals who share a paternal HLA antigen against which a mother has formed HLA-specific alloantibodies should be excluded from organ donation.

Adult↗
PubMed1996

A cell-saving non-radioactive limiting dilution analysis-assay for the combined determination of helper and cytotoxic T lymphocyte precursor frequencies.

We have developed a limiting dilution analysis-assay which makes the determination of both helper and cytotoxic T lymphocyte precursor frequencies possible. The way in which T helper precursor frequencies are determined in this combined assay is essentially the same as the method published previously. Experimental conditions for the combined assay have been optimized to obtain cytotoxic T lymphocyte precursor frequencies that are comparable to those determined in the assay routinely used in our laboratory. For all situations where the amount of available cell material is a limiting factor, it will be an advantage that with the same number of cells needed for a standard cytotoxic T lymphocyte precursor frequency determination, in the combined assay both helper and cytotoxic T lymphocyte precursor frequencies can be determined. This is especially convenient in the case of bone marrow transplantation, where evidence is accumulating that low or negative cytotoxic T lymphocyte and/or T helper precursor frequencies may be a prerequisite for a successful transplantation with a minimal risk of graft-versus-host disease.

Hematopoietic Stem Cells↗
PubMed1995

Relevance of pretransplant donor-specific T cell allorepertoire for human kidney graft survival.

In order to determine whether the donor-specific T cell allorepertoire evaluated in patients before transplantation can be predictive for kidney graft survival, a study has been set up in which the number and activation state of donor-specific T lymphocytes before transplantation were correlated to transplant survival time. Limiting dilution analysis assays were carried out to determine precursor frequencies of both T helper and cytotoxic T lymphocytes. The activation state of these cells was studied by evaluating the inhibitory capacity of cyclosporine on helper and cytotoxic T cells and/or a monoclonal antibody directed against CD8 on cytotoxic T cells. This study shows that neither a significant difference in the number nor activation state of donor-directed helper and cytotoxic T cells before transplantation could be detected when patients who acutely rejected their grafts were compared with patients who still had a well-functioning kidney graft after more than 10 years. Moreover, no significant differences in the donor-specific T cell repertoire were found when patients who had been subject to multiple rejection episodes were compared with patients who experienced few complications after transplantation. Therefore, we conclude that in individuals who have not been sensitized to HLA antigens of the donor, the donor-specific peripheral T cell allorepertoire prior to transplantation is not predictive of kidney graft survival.

Antibodies↗
PubMed1995

Cerebral blood flow in severe clinical head injury.

Following severe head injury, derangements of the cerebral vasculature and cerebral blood flow (CBF) often occur, rendering the brain at risk of secondary ischemia. Therefore, monitoring of CBF in head-injured patients is considered useful for understanding the pathophysiology and effects of therapy, although such monitoring has not yet become part of routine patient management in most centers. In this article, we review the current research on CBF in head injury. Understanding of the physiologic relationship between CBF and cerebral oxygen metabolism (CMRO2) is crucial in the interpretation of CBF values obtained in comatose head injured-patients. Although CMRO2 is reduced with coma, there is ample evidence to suggest that vulnerability of the brain to ischemia is in fact enhanced after traumatic injury. It is now well established that cerebral ischemia (CBF < or = 18 mL/100 g/min) is present in approximately 30% of cases within the first 6 hrs postinjury. In addition, early ischemia has been found to correlate with poor outcome and early mortality. Notably, early ischemia was present even with normal or restored blood pressure and arterial oxygenation, which suggests that other, nonsystemic causes of cerebral ischemia after traumatic brain injury exist. Although spasm of the larger cerebral arteries has been postulated as a possible cause of ischemia, recent measurements of cerebral blood volume are more compatible with compromise of the microcirculation, possibly due to perivascular swelling, with endothelial injury and leukocyte stasis. Disturbances of cerebrovascular CO2 reactivity and autoregulation appear to be less frequent than previously assumed. However, when present, such derangements do have consequences for therapy, in particular the management of blood pressure and cerebral perfusion pressure. Potential implications for patient management are discussed.

Brain↗
PubMed1993

Evaluation of regional cerebral blood flow in acute head injury by stable xenon-enhanced computerized tomography.

Measurement of regional cerebral blood flow (rCBF) in head-injured patients is considered useful for understanding the cerebral hemodynamics of brain trauma and for determining the optimal therapy. Most data thus far obtained with 133Xe clearance techniques have made only relative contribution, due to limitations of the 133Xe method. More recently, is has become possible to measure rCBF by xenon-enhanced computerized tomography (Xe-CT), which obviates most problems inherent to the 133Xe method. On the other hand, computational errors and concerns regarding the safety of xenon inhalation have thwarted the clinical use of Xe-CT. Recent advances in CT technology, however, have largely eliminated these problems. Xe-CT CBF measurements in severe head injury demonstrate a good correlation between CBF values obtained with 133Xe and Xe-CT. By consistently applying these studies in conjunction with conventional CT, information on very early flow derangements (within 1 to 2 hours after injury) can be obtained, in relation to anatomical lesions. Preliminary data reveal higher incidences of global and focal ischaemia than found previously. Local ischaemia tends to evolve to hyperemia in the ensuing days.

Brain↗
PubMed1992

Determination of cytotoxic T-lymphocyte precursor frequencies using europium labeling as a nonradioactive alternative to labeling with chromium-51.

We report on the use of europium (Eu) as a suitable nonradioactive alternative for target cell labeling in limiting dilution analysis (LDA) assays set up to determine cytotoxic T-lymphocyte precursor (CTLp) frequencies. A nonradioactive alternative to the commonly used chromium-51 (51Cr) release assay seems desirable because working with radioisotopes has some major disadvantages concerning possible health risks, environmental load, costs of facilities necessary for working with radioisotopes, and shelf life. Some groups have successfully applied the Eu release assay based on detection by time-resolved fluorometry, to tests in which NK- or LAK-cell activity or cytotoxic T-lymphocyte reactions were measured. This led to the investigation whether this method could also be applicable to the more specific determination of CTLp frequencies in LDA assays. After optimal labeling conditions had been established, the sensitivity of the Eu release assay was determined by performing several LDA assays in which the target cells were labeled with either Eu or radioactive 51Cr. When CTLp frequencies were compared, it was shown that the Eu release assay is at least as sensitive and specific as the 51Cr release assay. Moreover, although the labeling procedure takes longer, sample processing is much faster: only 1 second per sample. The fact that the Eu release assay is not radioactive enables the assay to be performed at any laboratory and even--because the frequency of CTLps may have implications for organ graft survival and for donor selection in bone marrow transplantation--to do so on a routine basis.

Cell Count↗
PubMed1992

Effect of hematocrit variations on cerebral blood flow and basilar artery diameter in vivo.

Despite observations that pial arterioles constrict with decreased blood viscosity or hemodilution, several investigators have found an inverse relationship between cerebral blood flow (CBF) and hematocrit (Hct) under physiological conditions. To investigate whether this is due to a dilation of the more proximal large cerebral arteries, in vivo responses of CBF and basilar artery to hemodilution and hemoconcentration were studied in 21 anesthetized normal cats, using a closed clival window model. An inverse correlation between Hct and CBF was found, but CBF responses were smaller than previously reported data suggest. Varying Hct between 60 and 120% of baseline caused CBF to vary between 140 and 90%, approximately. Moderate hemodilution was associated with a significant decrease (-4.4%) in basilar artery diameter (P less than 0.05), but other Hct manipulations had no consistent effect on basilar artery diameter. It is concluded that dilation of large cerebral arteries cannot account for the decreased cerebrovascular resistance following hemodilution but that a disproportionate reduction of in vivo viscosity must be responsible. Pial arteriolar constriction after hemodilution therefore probably reflects a normal autoregulatory adjustment of vasomotor tone to altered blood rheology, whereas changes in large artery caliber may serve to modulate microvascular pressure.

Animals↗