PubMed Health⌕ Search

Biomedical subjects

J Rademacher

Publications and source records attributed to J Rademacher.

At least 19 recordsLinked to original sources

Rectovaginal fistula after STARR procedure complicated by haematoma of the posterior vaginal wall: report of a case.

We report the case of a patient treated with the stapled transanal rectal resection (STARR) procedure for obstructed defecation, who developed an early postoperative haematoma of the posterior vaginal wall and, after 30 days, a rectovaginal fistula (RVF), even though the intervention had been performed according to the standardized technique. After clinical examination and three-dimensional anal endosonography, we carried out a successful surgical correction with double vaginal and rectal flaps with repair of the rectovaginal septum and without faecal diversion. The STARR procedure, even if performed according to a rigorous application of the methodological standards, may be followed by a RVF possibly due to a blood collection leading to ischaemia of the vaginal wall.

Female↗

[Immunomodulation after combined spleen and kidney transplantation in swine].

AIM: Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine. METHODS: Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection. RESULTS: Controls died from kidney failure within 10(th) POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05). CONCLUSIONS: These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.

Animals↗

[Liver transplantation in swine: a model for tolerance induction].

AIM: The liver as a solid graft has a known immunological privilege. Its tolerogenic property has been demonstrated in rodents. In humans the onset of chronic rejection and the severity of such complication is less frequent after liver transplantation compared to other organs. The underlying events whose effect is graft acceptance instead of rejection should be further investigated. Their control could open new ways to decrease the need for long-term immunosuppression after transplantation of other organs. Aim of this study is to evaluate a model of liver transplantation in swine as a preliminary step for immunological studies. METHODS: Ten outbred Landrace/Large White mismatched swine underwent to liver transplantation with a simple passive portocaval jugular bypass. The onset of rejection was monitored daily by liver function test. After death or sacrifice the liver parenchyma was studied to evaluate tissue damage and inflammatory infiltrate. RESULTS: The postoperative liver function showed a critical period for organ rejection about postoperative day 5. The animals that survived longer were sacrificed with a normal biochemical hepatic function. However, histology consistently showed a pattern of mild rejection in a still preserved architecture. CONCLUSIONS: The evidence of a prolonged liver function in a rejecting model of liver transplantation makes this model suitable for studies of tolerance induction.

Animals↗

[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection].

AIM: Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats. METHODS: Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts. RESULTS: In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2. CONCLUSIONS: Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.

Animals↗

Stereotaxic localization, intersubject variability, and interhemispheric differences of the human auditory thalamocortical system.

Population (probability) maps of cytoarchitectonically defined cortical maps and myeloarchitectonically defined subcortical fiber tracts of the human brain became recently available. These maps can be used for the precise anatomical localization of activated foci as found in functional imaging studies. The aim of this study is to evaluate population maps of the human acoustic radiation (AR) for the purpose of brain mapping studies. Thus, a stereotaxic 3-D representation of the human AR was computed which includes myeloarchitectonic probabilistic maps of AR and its thalamic origin, i.e. the cytoarchitectonically defined medial geniculate nucleus (MGN). These maps were compared with earlier, mostly schematic drawings of AR and MGN. To generate these maps, the degree of intersubject variability of AR and MGN in each stereotaxic position was quantified for the standard axes (x, y, and z) of the reference space in a series of 10 adult human postmortem brains. The results show that the location and volumes of AR and MGN vary considerably between individuals and hemispheres. It is demonstrated that this striking degree of spatial variations may lead to structural-functional mismatch in brain mapping studies based on the Talairach atlas (discrepancy maps). Furthermore, the volumetric measures showed no hemispheric asymmetry for AR and MGN. In contrast to earlier maps, our approach provides microanatomically defined data as a probabilistic reference system for research in auditory structure-function relationships.

Adult↗

Human primary auditory cortex in women and men.

Specific patterns of anatomical symmetry or asymmetry have been associated with sex differences in human brain structure and function. An observer-independent cytoarchitectonic method for the quantification of cell volume densities and areal borders was used to investigate the size and microstructure of primary auditory cortex (Brodmann area 41) in female (n = 14) and male (n = 13) postmortem brains. The total brain volume-adjusted volume of the primary auditory cortex was significantly larger in women than in men bilaterally. Inverse asymmetry towards the right side, as opposed to well-known asymmetries towards the left side, was more frequent in women. Laminar cell volume densities of BA 41 showed no gender effect. The morphometric data confirm (in part) gender differences in the cerebral organization of primary auditory cortex.

Adult↗

Probabilistic mapping and volume measurement of human primary auditory cortex.

Despite their potential utility in clinical and research settings, the range of intra- and interindividual variations in size and location of cytoarchitectonically defined human primary auditory cortex (PAC) is largely unknown. This study demonstrates that gyral patterns and the size and location of PAC vary independently to a considerable degree. Thus, the cytoarchitectonic borders of PAC cannot be reliably inferred from macroscopic-MR visible-anatomy. Given the remarkable topographical variability of architectonic areal borders, standard brain mapping which is made solely on the basis of macroanatomic landmarks may lead to structural-functional mismatch. Consequently, interpretations of individual auditory activity patterns might often be inaccurate. In view of the anatomic discrepancies, we generated probability maps of PAC in which the degree of intersubject overlap in each stereotaxic position was quantified. These maps show that the location of PAC in Talairach space differs considerably between hemispheres and individuals. In contrast to earlier cytoarchitectonic work which is based in most cases on studies of single brains, our systematic approach provides extensive microanatomic data as a reference system for studies of human auditory function.

Adult↗

Human primary auditory cortex: cytoarchitectonic subdivisions and mapping into a spatial reference system.

The transverse temporal gyrus of Heschl contains the human auditory cortex. Several schematic maps of the cytoarchitectonic correlate of this functional entity are available, but they present partly conflicting data (number and position of borders of the primary auditory areas) and they do not enable reliable comparisons with functional imaging data in a common spatial reference system. In order to provide a 3-D data set of the precise position and extent of the human primary auditory cortex, its putative subdivisions, and its topographical intersubject variability, we performed a quantitative cytoarchitectonic analysis of 10 brains using a recently established technique for observer-independent definition of areal borders. Three areas, Te1.1, Te1.0, and Te1.2, with a well-developed layer IV, which represent the primary auditory cortex (Brodmann area 41), can be identified along the mediolateral axis of the Heschl gyrus. The cell density was significantly higher in Te1.1 compared to Te1.2 in the left but not in the right hemisphere. The cytoarchitectonically defined areal borders of the primary auditory cortex do not consistently match macroanatomic landmarks like gyral and sulcal borders. The three primary auditory areas of each postmortem brain were mapped to a spatial reference system which is based on a brain registered by in vivo magnetic resonance imaging. The integration of a sample of postmortem brains in a spatial reference system allows one to estimate the spatial variability of each cytoarchitectonically defined region with respect to this reference system. In future, the transfer of in vivo structural and functional data into the same spatial reference system will enable accurate comparisons of cytoarchitectonic maps of the primary auditory cortex with activation centers as established with functional imaging procedures.

Adult↗

Variability and asymmetry in the human precentral motor system. A cytoarchitectonic and myeloarchitectonic brain mapping study.

The morphology of the region of the primary motor cortex in the human brain is variable, and putative asymmetries between the hemispheres have been noted since the beginning of last century. Such variability may confound the results of clinical lesion or functional activation studies. We measured Brodmann area (BA) 4 and the identifiable precentral component of the pyramidal tract (PRPT) in 11 human post-mortem brains using techniques of quantitative cytoarchitectonic and myeloarchitectonic image analysis. Topography and variability in the localization of architectonic borders were analysed and mapped to a computerized spatial reference system, which consists of an individual in vivoMRI brain. All maps were superimposed to produce probabilistic maps of BA 4 and PRPT which can be co-registered with any image of brain structure or function that has also been transformed to Talairach coordinates. These maps can be readily applied to future brain mapping studies. We observed a considerable degree of variability between hemispheres (intra-individual) and between brains (inter-individual). The variation zones of BA 4 and PRPT differ from the templates of the Talairach atlas. Voxel-based morphometry shows significant side differences with larger volumes of PRPT in the left hemisphere than in the right hemisphere. This larger volume of the descending cortical motor fibres may be related to the known left-hemisphere dominance for handedness in >90% of the population. In contrast, BA 4 was symmetrically organized. The lack of a significant correlation between the size of BA 4 and the size of PRPT may relate to the fact that additional non-primary motor and sensory cortices contribute to the origins and size of the pyramidal tract proper.

Adult↗

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI.

We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated amino-acid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures.

Aphasia↗

Measuring in vivo myelination of human white matter fiber tracts with magnetization transfer MR.

Precise characterization of white matter pathways is important for the understanding of structural-functional relationships in the human brain. While it is known from postmortem studies that the connectivity of cortical areas is conveyed by projection, commissural, and association fibers, most clinical studies disregard useful information about specific fiber tracts. Magnetization transfer (MT) MR detects the relative proportion of free mobile protons and immobile protons bound to macromolecules. MT values correlate with histopathology and it has been proposed that in the white matter, the amount of magnetization transfer correlates with the degree of myelination. Thus, MT-MR provides measures that may reflect more accurately the physiology and natural course of diseases involving the white matter. We applied this quantitative in vivo method to five children at different ages to determine whether the maturational changes of distinct fiber tracts could be measured. All regions of interest were localized by means of Brodmann's original descriptions and the additional use of reconstructed 3D-matched data from 10 myelin-stained human brain specimens. With this atlas-guided approach we localized and measured 26 supratentorial white matter fiber tracts in each hemisphere, connecting to primary as well as association cortices. All fiber tracts showed consistent age-related MT changes and the strongest effects were found in those tracts projecting to the primary cortical areas. These results suggest that our method is suitable for in vivo MT measurements in specific fiber tracts. It can provide data that relate to myelination during ontogenesis or myelination delays in myelin disorders. In the clinical domain, the focus on specific fiber tracts appears to be advantageous over standard approaches, because such system of parcellation is based on the functional anatomy of the white matter. Consequently, it may be especially useful for topical analysis in neurology allowing the assessment of the functional consequences of white matter damage as well as the effectiveness of treatments in patients with any lesion that can be visualized by MRI.

Acoustic Stimulation↗

Cerebral microembolism, a disease marker for ischemic cerebrovascular events in the antiphospholipid syndrome of systemic lupus erythematosus?

OBJECTIVES: We investigated whether the detectability of microembolic Doppler signals (MES) in the intracranial circulation may help to define the individual cerebrovascular risk in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Retrospective cross-sectional study of 70 patients with SLE with or without APS, and 30 controls with a history of cerebral ischemia of unknown cause. Of all patients, 38 had a clinical history of APS and 32 did not. RESULTS: 15 patients with APS (39%) showed MES. In contrast, all patients without APS and 29 of 30 controls were microemboli-negative. MES were more strongly associated with cerebrovascular symptoms than with APS, antiphospholipid antibodies, or cardiac pathology. The time elapsed since the last ischemic cerebrovascular symptom was significantly shorter in microemboli-positive patients than in microemboli-negative patients (P<0.001). CONCLUSION: MES may be related to disease activity in patients with SLE and APS. Their detection may help to assess individual cerebrovascular risk and contribute to therapeutic decision making and therapeutic monitoring.

Adolescent↗

[Whole pancreatic transplantation and islet transplantation. Experiment notes].

BACKGROUND: The results of pancreas transplantation have greatly improved in recent years. The path to further improvements goes through extensive experimental researches. METHODS: This study describes the effects of different procedures as hemodynamic asset and postoperative outcome. Twenty-nine swine underwent a total pancreatectomy, and were stratified into five groups. Group one (n = 5) served as control. Group two (n = 7) was autotransplanted. Group three (n = 6) and group four (n = 6) underwent allotransplantation; the first without immunosuppression and the second treated with cyclosporine and steroids. In group five (n = 5) Langerhans Islets transplantation was performed. RESULTS: Survival was different depending on which methodology was applied. The postoperative survival was 7 +/- 2 days in group one, 24 +/- 16 days in group two, 17 +/- 7 days in group three, 27 +/- 8 days in group four and 12 +/- 6 days in group five. CONCLUSIONS: The postoperative glucose control was normal in group two and group four while a severe diabetes appeared in group one (group 1 vs group 2: p < 0.05) and in group three during acute graft rejection after the 12th postoperative day (group 3 vs group 4: p < 0.05). Glycemia was slightly controlled in group five. The intraoperative hemodynamic status was evaluated at the time of pancreatectomy, harvesting, revascularization, and when surgery was over. Among the different parameters studied (mean arterial and pulmonary pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), a statistically significant difference between group one and group five (p < 0.05) was observed.

Animals↗

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I].

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.

Animals↗

[The hemodynamic effects of the in-vivo administration of insulin-like growth-factor I].

BACKGROUND: Recent studies have demonstrated that IGF-I has several biological activities that correlate with the GH axis, by acting as a cell protecting factor and a promoting compound in different tissues and organs. Our latest findings have demonstrated a potential application of IGF-I in the treatment of postischemic renal injury, which frequently appears after a kidney transplant. The beneficial effect of the renal postoperative recovery probably correlates with the regulation of the vascular tone, in which IGF-I plays a role with other cytokines. However, this rises the question whether IGF-I has any effect on the general hemodynamic status. This study was designed to underline the intraoperative hemodynamic effect of exogenous IGF-I in an experimental setting of renal transplantation in swine. METHODS: Twelve female swine underwent a left renal autotransplantation. At the reperfusion the animals were separated in two groups. Group one served as control. Group two received 400 micrograms of IGF-I (added to the flushing solution). The animals were kept under complete hemodynamic monitoring over the operation. RESULTS: Among the different parameters studied (mean arterial pressure, mean pulmonary arterial pressure, pulmonary wedge pressure, central venous pressure, cardiac output, oxygen extraction ratio, systemic vascular resistance, oxygen delivery and oxygen consumption), any statistically significant difference between group one and two were observed. CONCLUSIONS: While the clinical administration of IGF-I requires further studies, the in vivo administration of this peptide is apparently well tolerated, and does not cause any hemodynamic instability to the operation.

Analysis of Variance↗

Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND: Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS: We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS: Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS: In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Animals↗