Biomedical subjects

C Schultz

Publications and source records attributed to C Schultz.

At least 19 recordsLinked to original sources

PubMed2006

Physiological effects of lower extremity functional electrical stimulation in early spinal cord injury: lack of efficacy to prevent bone loss.

STUDY DESIGN: Controlled, repeat-measures study. OBJECTIVES: To determine if functional electrical stimulation (FES) can affect bone atrophy in early spinal cord injury (SCI), and the safety, tolerance and feasibility of this modality in bone loss remediation. SETTING: Spinal Injuries Units, Royal Adelaide Hospital and Hampstead Rehabilitation Centre, South Australia. METHODS: Patients with acute SCI (ASIA A-D) were allocated to FES (n=23, 28+/-9 years, C4-T10, 13 Tetra) and control groups (CON, n=10, 31+/-11 years, C5-T12, four Tetra). The intervention group received discontinuous FES to lower limb muscles (15 min sessions to each leg twice daily, over a 5-day week, for 5 months). Dual energy X-ray absorptiometry (DEXA) measured total body bone mineral density (tbBMD), hip, spine BMD and fat mass (FM) within 3 weeks, and 3 and 6 months postinjury. RESULTS: FES and CON groups' tbBMD differed significantly at 3 months postinjury (P<0.01), but not thereafter. Other DEXA measures (hip, spine BMD, FM) did not differ between groups at any time. No adverse events were identified. CONCLUSION: Electrically stimulated muscle activation was elicited, and tetanic effects were reproducible; however, there were no convincing trends to suggest that FES can play a clinically relevant role in osteoporosis prevention (or subsequent fracture risk) in the recently injured patient. The lack of an osteogenic response in paralysed extremities to electrically evoked exercise during subacute and rehabilitation/recovery phases cannot be fully explained, and may warrant further evaluation.

Adipose Tissue↗

PubMed2006

Degeneration of ingestion-related brainstem nuclei in spinocerebellar ataxia type 2, 3, 6 and 7.

Dysphagia, which can lead to nutritional deficiencies, weight loss and dehydration, represents a risk factor for aspiration pneumonia. Although clinical studies have reported the occurrence of dysphagia in patients with spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3), type 6 (SCA6) and type 7 (SCA7), there are neither detailed clinical records concerning the kind of ingestive malfunctions which contribute to dysphagia nor systematic pathoanatomical studies of brainstem regions involved in the ingestive process. In the present study we performed a systematic post mortem study on thick serial tissue sections through the ingestion-related brainstem nuclei of 12 dysphagic patients who suffered from clinically diagnosed and genetically confirmed spinocerebellar ataxias assigned to the CAG-repeat or polyglutamine diseases (two SCA2, seven SCA3, one SCA6 and two SCA7 patients) and evaluated their medical records. Upon pathoanatomical examination in all of the SCA2, SCA3, SCA6 and SCA7 patients, a widespread neurodegeneration of the brainstem nuclei involved in the ingestive process was found. The clinical records revealed that all of the SCA patients were diagnosed with progressive dysphagia and showed dysfunctions detrimental to the preparatory phase of the ingestive process, as well as the lingual, pharyngeal and oesophageal phases of swallowing. The vast majority of the SCA patients suffered from aspiration pneumonia, which was the most frequent cause of death in our sample. The findings of the present study suggest (i) that dysphagia in SCA2, SCA3, SCA6 and SCA7 patients may be associated with widespread neurodegeneration of ingestion-related brainstem nuclei; (ii) that dysphagic SCA2, SCA3, SCA6 and SCA7 patients may suffer from dysfunctions detrimental to all phases of the ingestive process; and (iii) that rehabilitative swallow therapy which takes specific functional consequences of the underlying brainstem lesions into account might be helpful in preventing aspiration pneumonia, weight loss and dehydration in SCA2, SCA3, SCA6 and SCA7 patients.

Adult↗

PubMed2006

Immunosuppressive activity of the immunophilin-binding drug Sanglifehrin A in human whole blood: potent inhibition of interleukin-6 produced by lymphocytes and monocytes.

The novel immunosuppressant Sanglifehrin A (SFA) is an immunophilin-binding metabolite with a yet unidentified mechanism of action. Several reports demonstrated the effects of SFA on proliferation and cytokine production of purified T cells with in part different results. However, less is known about the impact of SFA on the regulation of innate immune responses. We used a whole blood assay to investigate the impact of SFA on monocyte responses and T-lymphocyte activity/proliferation upon lipopolysaccharide (LPS) stimulation and anti-CD3/anti-CD28 costimulation, respectively. SFA was found to inhibit interleukin (IL)-2 protein expression of T lymphocytes. Whereas IL-2 mRNA expression was significantly reduced after 4 h of costimulation, the mRNA expression of IL-4 and IL-6 but not tumour necrosis factor (TNF)-alpha was inhibited by SFA both after 4 and 24 h of costimulation. The production of IL-2 and IL-6 protein in T lymphocytes was even strongly affected by SFA than the mRNA expression of the respective cytokine. Unlike other immunophilin-binding immunosuppressants, SFA also inhibited LPS-induced IL-6 and TNF-alpha mRNA and protein expression. At the single cell level, SFA was demonstrated to block the intracellular production of IL-6 in CD14+ monocytes but not the expression of other proinflammatory cytokines such as IL-8 and TNF-alpha. On the basis of these data, we propose that SFA may have a significant effect on the initiation and direction of immune responses. Considering the pleiotropic role of bioactive IL-6 production at the interface of innate and acquired immunity in a variety of disease conditions, it was found that these novel aspects of the unique immunosuppressive action could strongly impact on future clinical application of SFA.

Cytokines↗

PubMed2006

Low molecular weight quaternised chitosan (11): in vitro assessment of absorption enhancing properties.

N-Trimethyl chitosan chloride (TMC; high molecular weight) and N-trimethyl chitosan oligosaccharide (TMO; low molecular weight) with different degrees of quaternisation were synthesised and evaluated for their absorption enhancing properties across mucosal epithelia. These quaternised chitosan derivatives (0.0625% w/v-0.5% w/v) showed a significant decrease in the transepithelial electrical resistance (TEER) of cultured rabbit tracheal epithelial cell monolayers as compared to the control. The degree of quaternisation and concentration of the compounds influenced the extent of the reduction in TEER. Higher degrees of quaternisation and an increase in the concentration of the compound were associated with a more pronounced reduction in the TEER. The TMO derivatives seemed to be more effective in lowering the TEER of tracheal cell monolayers as compared to the TMC polymers. Ciliary beat frequency (CBF) is the main defence mechanism of the respiratory tract and is therefore a useful parameter in evaluating the toxicity of nasally administered drugs and additives. The effect of the synthesised chitosan derivatives on the CBF of human nasal epithelial cells at pH 7.4 was determined by a method based on an analogue contrast enhancement technique. The TMO oligomers exhibited lower inhibition of the CBF of human nasal epithelial cells compared to that of the TMC polymers. It was proposed that this reduced effect on the CBF is due to the lower viscosity and molecular weight of TMO. However, no acute toxicity was found with any of the synthesised chitosan derivatives by means of the CBF tests conducted in this study.

Animals↗

PubMed2005

Involvement of the cranial nerves and their nuclei in spinocerebellar ataxia type 2 (SCA2).

Although the cranial nerves, their nuclei and related fiber tracts are crucial for a variety of oculomotor, somatomotor, somatosensory, auditory, vestibular-related, autonomic and ingestion-related functions, knowledge regarding the extent of their involvement in spinocerebellar ataxia type 2 (SCA2) patients is incomplete. Accordingly, we performed a pathoanatomical analysis of these structures in six clinically diagnosed SCA2 patients. Unconventionally thick serial sections through the brainstem stained for lipofuscin pigment (aldehyde-fuchsin) and Nissl material (Darrow red) showed that all oculomotor, somatomotor, somatosensory, auditory, vestibular and autonomic cranial nerve nuclei may undergo neurodegeneration during SCA2. Similarly, examination of myelin-stained thick serial sections revealed that nearly all cranial nerves and associated fiber tracts may sustain atrophy and myelin loss in SCA2 patients. In view of the known functional role of the affected cranial nerves, their nuclei and associated fiber tracts, the present findings provide appropriate pathoanatomical explanations for some of the disease-related and unexplained symptoms seen in SCA2 patients: double vision, gaze palsy, slowing of saccades, ptosis, ingestion-related malfunctions, impairments of the optokinetic nystagmus and the vestibulo-ocular reaction, facial and tongue fasciculation-like movements, impaired centripetal transmission of temperature-related information from the face, dystonic posture of the neck, as well as abnormalities of the brainstem auditory evoked potentials.

Adolescent↗

PubMed2005

Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum.

The pre-cerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the pre-cerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the pre-cerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.

Adolescent↗

PubMed2005

[Telemonitoring in chronic heart failure patients. Which diagnostic finding prevents hospital readmission?].

Heart failure exhibits a significant clinical and health economic problem. The implementation of new therapeutic strategies favorably affecting the course of disease is still insufficient in day-to-day practice. Thus, the usage of telemedicine offers a central instrument for service and information, so that an optimized therapy can be achieved by consequent surveillance of the patient with chronic heart disease. Predefined vital parameters are automatically transmitted to the telemedicine center; if individually predefined limits are exceeded, therapeutic means are immediately initiated. For the patient, the center is attainable 24 h throughout the year in case he experiences cardio-pulmonary symptoms. This patient-oriented usage of technology should not replace the physician-patient relationship, but improves and supports the participation and self-management of patients. Furthermore, the results show that this technology can significantly reduce the amount of emergency physician services, hospital admissions and primary care physician visits, and displays for health economics purposes a clearly more cost-effective treatment strategy, while allowing for additional costs inherent to the system. The usage of telemonitoring in chronic heart failure patients may be a trendsetting form of care, which can be used to drastically optimize the information and data flow between patient, hospital and primary care physician individually and at any time.

Blood Pressure Determination↗

PubMed2005

Bilateral symmetry of the human metacarpal: implications for sample size calculations.

OBJECTIVE: The aim of this study was to assess the three-dimensional mechanical symmetry of the human second metacarpal and provide sample size estimates for future mechanical intervention studies of the metacarpal. DESIGN: Bone densitometry and digital image analysis were used to assess the morphometric, geometric and densitometric symmetry of the second human metacarpal. BACKGROUND: An assessment of the left-right mechanical symmetry of the human metacarpal is important in considering the suitability of using the contralateral metacarpal as a control and in providing sample size calculations for future studies involving a mechanical intervention to the metacarpal such as implantation of a metacarpophalangeal prosthesis. METHODS: Metaphyseal sectional areas, diaphyseal cortical sectional areas, second moments of area, average periosteal and medullary radii and bone densities were measured at nine transverse levels for each of seven pairs of index metacarpals using computed tomography and bone densitometry. Polar Fourier regression was used to assess the morphometry of sectional periosteal and endosteal boundaries. Differences between clinically important left-right parameters were assessed. RESULTS: Mean differences between clinically important left-right parameters were small (<3%) and similar to the degree of experimental precision. There were strong significant left-right correlations for the morphometric, geometric and densitometric parameters considered, indicating a high degree of bilateral mechanical symmetry. CONCLUSIONS: The contralateral bone is a suitable control for mechanical intervention studies of the human metacarpal, and the use of bilateral pairing results in an important reduction in sample size. RELEVANCE: Responses to mechanical interventions on the human metacarpal, such as implantation of a metacarpophalangeal prosthesis, are generally unknown. The degree of left-right mechanical symmetry in the human metacarpal provides a measure of the advantage of using paired design studies to address these questions.

Anatomy, Cross-Sectional↗

PubMed2005

Daclizumab induction therapy associated with tacrolimus-MMF has better outcome compared with tacrolimus-MMF alone in pediatric living donor liver transplantation.

AIMS: Immunosuppression therapy for the control of immunologic rejection is a key aspect in liver transplantation. The objective of this study was to evaluate induction therapy with daclizumab (DAC) in living donor liver transplantation (LDLT) in children. METHODS: We compared 2 different immunosuppression protocols in 30 children undergoing LDLT. The patients were divided into 2 groups: 12 patients received tacrolimus with mycophenolate mofetil (TAC-MMF), and 18 patients received tacrolimus with MMF and DAC induction therapy at days 0 and 14 after LDLT (DAC-TAC-MMF). Both groups were similar with regard to age, sex, weight, and indication for liver transplantation. The incidence of biopsy-proved rejection episodes, posttransplantation lymphoproliferative disease (PTLD), and renal dysfunction were evaluated. Tacrolimus levels at posttransplantation day 14 and at 2 months after transplantation were compared in the 2 groups. RESULTS: Acute rejection episodes were observed in 8 patients in the TAC-MMF group (66%), and none in the DAC-TAC-MMF group (0%; P < .05). Neither PTLD nor renal dysfunction was seen in any patient. Mean Tacrolimus level on posttransplantation day 14 was 10.67 +/- 5.4 ng/mL in the TAC-MMF group and 5.65 +/- 3.6 ng/mL in the DAC-TAC-MMF group (P < .05). After the second month the mean tacrolimus levels were 7.2 +/- 2.9 ng/mL and 6.8 +/- 3.5 ng/mL in the TAC-MMF and DAC-TAC-MMF groups, respectively. (P = NS). CONCLUSION: Induction therapy with DAC is safe and associated with a lower incidence of rejection episodes among children undergoing LDLT.

Adrenal Cortex Hormones↗

PubMed2005

Cytokine responses correlate differentially with age in infancy and early childhood.

The functional differentiation of immune cells at early age plays a central role in immune physiology, e.g. for the sufficient eradication of pathogens. However, imbalances in effector cell responses may also have an impact in the pathophysiology of childhood diseases such as atopy and autoimmune disorders. As information on immune cell responses in infancy and early childhood is scarce, we conducted an observational, cross-sectional study in healthy newborns (n = 18), infants and young children (n = 54) aged 1-96 months and adult controls (n = 19) to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13-actate/ionomycin stimulation and LPS-induced IL-12 expression in monocytes. The intracellular expression of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha (R = 0.748, P < 0.0001; R = 0.784, P < 0.0001, respectively) and interleukin (IL)-2 protein expression (R = 0.384, P = 0.008) was demonstrated to increase progressively with age. While a correlation between IL-4 protein expression and age was noted (R = 0.342, P = 0.007), the levels of IL-5 and IL-10 protein expression tended to be regulated on an individual basis during infancy and early childhood. An age correlation was also observed for intracellular IL-12 expression (R = 0.331, P = 0.009) in monocytes. These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical-therapeutic monitoring of immunological status in various childhood diseases.

Aging↗

PubMed2005

Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2.

The involvement of the thalamus during the course of the currently known polyglutamine diseases is still a matter of debate. While it is well-known that this diencephalic nuclear complex undergoes neurodegeneration in some polyglutamine diseases such as Huntington's disease (HD), it has remained unclear whether and to what extent the thalamus is also involved in spinocerebellar ataxia type 2 (SCA2) patients. Encouraged by our recent post-mortem findings in one German SCA2 patient and the results of a recent nuclear magnetic resonance (NMR) study, we extended our pathoanatomical analysis to serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of four additional German and Cuban SCA2 patients. According to this analysis the thalamus is consistently affected by the destructive process of SCA2. In particular, during our study we observed a consistent involvement of the lateral geniculate body, the lateral posterior, ventral anterior, ventral lateral, ventral posterior lateral, and ventral posterior medial thalamic nuclei as well as the extraterritorial reticular nucleus. In four of the SCA2 cases studied additional damage was seen in the inferior and lateral nuclei of the pulvinar, whereas in the minority of the patients a subset of the limbic nuclei of the thalamus (i.e. anterodorsal, anteroprincipal, laterodorsal, fasciculosus, mediodorsal, central lateral, central medial, cucullar, and paracentral nuclei, medial nucleus of the pulvinar) underwent neurodegeneration. These interindividual differences in the distribution pattern of thalamic neurodegeneration indicate that the thalamic nuclei differ in their proclivities to degenerate in SCA2 and may suggest that they become involved at different phases in the evolution of the underlying degenerative process.

Adult↗

PubMed2005

The impact of argyrophilic grain disease on the development of dementia and its relationship to concurrent Alzheimer's disease-related pathology.

Argyrophilic grain disease (AGD) constitutes a neurodegenerative disorder that occurs in the brains of the elderly and affects 5% of all patients with dementia. Tau protein-containing lesions known as argyrophilic grains and located predominantly in limbic regions of the brain characterize this disease. Dementia is encountered in only a subset of cases that display the morphological pattern of AGD. The aim of this study is to determine the role of concurrent Alzheimer's disease (AD)-related pathology for the development of dementia in AGD patients. A total of 204 post-mortem brains from 30 demented and 49 nondemented AGD patients, 39 AD patients, and from 86 nondemented controls without AGD were staged for AD-related neurofibrillary tangles (NFTs) as well as amyloid beta-protein (Abeta) deposition. To identify differences in AD-related pathology between demented and nondemented AGD cases, and to differentiate the pattern of AD-related changes in demented and nondemented AGD cases from that seen in AD and nondemented controls, we statistically compared the stages of Abeta and NFT distribution among these groups. Using a logistic regression model, we showed that AGD has a significant effect on the development of dementia beyond that attributable to AD-related pathology (P < 0.005). Demented AGD cases showed lower stages of AD-related pathology than did pure AD cases but higher stages than nondemented AGD patients. AGD associated dementia was seen in the presence of NFT (Braak)-stages II-IV and Abeta-phases 2-3, whereas those stages were not associated with dementia in the absence of AGD. In conclusion, AGD is a clinically relevant neurodegenerative entity that significantly contributes to the development of dementia by lowering the threshold for cognitive deficits in the presence of moderate amounts of AD-related pathology.

Aged↗

PubMed2005

Spinocerebellar ataxia type 7 (SCA7): first report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat.

Spinocerebellar ataxia type 7 (SCA7) represents a very rare and severe autosomal dominantly inherited cerebellar ataxia (ADCA). It belongs to the group of CAG-repeat or polyglutamine diseases with its underlying molecular genetical defect on chromosome 3p12-p21.1. Here, we performed a systematic study of the neuropathology on unconventional thick serial sections of the first available brain tissue of a genetically confirmed late-onset SCA7 patient with a very short CAG-repeat expansion. Along with myelin pallor of a variety of central nervous fiber tracts, we observed i) neurodegeneration in select areas of the cerebral cortex, and ii) widespread nerve cell loss in the cerebellum, thalamus, nuclei of the basal ganglia, and brainstem. In addition, upon immunocytochemical analysis using the anti-polyglutamine antibody 1C2, immunopositive neuronal intranuclear inclusions bodies (NI) were observed in all cerebellar regions, in all parts of the cerebral cortex, and in telencephalic and brainstem nuclei, irrespective of whether they underwent neurodegeneration. These novel findings provide explanations for a variety of clinical symptoms and paraclinical findings of both our and other SCA7 patients. Finally, our immunocytochemical analysis confirms previous studies which described the presence of NI in obviously degenerated brain and retinal regions as well as in apparently well-preserved brain regions and retina of SCA7 patients.

Aged↗

PubMed2005

Comparative tissue factor pathway inhibitor release potential of heparins.

Tissue factor pathway inhibitor (TFPI) is released following the administration of unfractionated heparin, low-molecular-weight heparins, defibrotide and PI-88. In this study, the comparative effects of heparin, a low-molecular-weight heparin-gammaparin and a heparin-derived oligosaccharide mixture-subeparin (C3) were studied on functional and immunologic tissue factor pathway inhibitor activity levels in a non-human primate (Macaca mulatta) model. The dose-dependent effect was studied following intravenous and subcutaneous administration. Following the administration of 1 mg/kg of heparin, gammaparin, and C3, the functional levels of TFPI at 5 minutes were 2.40, 2.56, and 1.08 U/mL and the corresponding TFPI immunologic levels were 4.3-, 4.0-, and 2.1-fold, increased, respectively, over the baseline value. From these results, it can be concluded that heparin and gammaparin produced similar levels of TFPI release. Hence, gammaparin and heparin have similar TFPI release potential despite their differences in molecular weight. The influence of molecular weight, charge density, and interactions with heparin cofactor II on TFPI release are also discussed.

Animals↗

PubMed2005

Specific alteration of the Bax/Bcl2 ratio and cytochrome c without execution of apoptosis in the hippocampus of aged baboons.

PURPOSE: During ageing, there may be an age-associated loss of particular nerve cells in specific brain areas. Recent studies highlight the role of apoptosis in the normal ageing of the brain, heart, and skeletal muscle. Particular attention is paid to the role of cytochrome c release from mitochondria and alterations in the pro- and anti-apoptotic proteins, Bax and Bcl-2, respectively. The aim of this study was to investigate the potential occurrence of apoptosis in the hippocampus of aged baboons. METHODS: we have used the baboon as a potential non-human primate model for age-related pathology which afflicts the human brain. The TUNEL staining method was used to characterise the apoptotic cell death. For immunocytochemistry, antibodies directed against activated caspase-3, cytochrome c, Bcl-2 and Bax proteins were used. RESULTS: Our results show that in hippocampi of aged baboons the immunoreactivities of the antiapoptotic agent Bcl-2 was not prominently changed, of the proapoptotic agent Bax was upregulated, of the cytochrome c was redistributed, and that caspase-3 was not activated. The TUNEL-staining method revealed no apoptotic cell death in hippocampi of aged baboons. CONCLUSIONS: This demonstrates that a specific alteration of the Bax/Bcl2 ratio occurs in the ageing baboon hippocampus which may directly influence the release of cytochrome c even without commitment to apoptosis.

Aging↗

PubMed2004

Damage to the reticulotegmental nucleus of the pons in spinocerebellar ataxia type 1, 2, and 3.

BACKGROUND: The reticulotegmental nucleus of the pons (RTTG) is among the precerebellar nuclei of the human brainstem. Although it represents an important component of the oculomotor circuits crucial for the accuracy of horizontal saccades and the generation of horizontal smooth pursuits, the RTTG has never been considered in CAG repeat or polyglutamine diseases. METHODS: Thick serial sections through the RTTG of 10 patients with spinocerebellar ataxias (SCAs) assigned to the CAG repeat or polyglutamine diseases (2 SCA-1 patients, 4 SCA-2 patients, and 4 SCA-3 patients) were stained for neuronal lipofuscin pigment and Nissl material. RESULTS: The unconventionally thick tissue sections revealed the hitherto overlooked involvement of the RTTG in the degenerative processes underlying SCA-1, SCA-2, and SCA-3, whereby in one of the SCA-1 patients, in two of the SCA-2 patients, and in all of the SCA-3 patients, the RTTG underwent a conspicuous loss of its nerve cells. CONCLUSIONS: Neurodegeneration may not only affect the cranial nerve nuclei (i.e., oculomotor and abducens nuclei) of SCA-1, SCA-2 and SCA-3 patients integrated into the circuits, subserving accuracy of horizontal saccades and the generation of horizontal smooth pursuits, but likewise involves the premotor networks of these circuits. This may explain why the SCA-1, SCA-2, and SCA-3 patients in this study with a heavily damaged reticulotegmental nucleus of the pons developed dysmetric horizontal saccades and impaired smooth pursuits during the course of the disease.

Adolescent↗

PubMed2004

Results of 60 consecutive hepatectomies for pediatric living donor liver transplantation.

Several technical improvements have been made to increase donor pool for pediatric liver transplantation, including reduced-size grafts, split-liver, and recently living donors. The objective of the present study is to report our single-center experience with 60 hepatectomies for living donor liver transplantation in pediatric recipients between June 2000 and December 2002. Donor workup consisted of a complete history and physical examination followed by laboratory test and liver function tests. Graft size was estimated using computed tomography scan or abdominal ultrasound. Liver biopsy was performed in all donors. Arteriogram was performed to evaluate hepatic arterial anatomy. All donors survived the procedure. Only seven patients experienced complications (10.2%), most of which were short term. We conclude that liver living donation for pediatric population is a safe procedure.

Adolescent↗

PubMed2004

Dose-dependent immunomodulatory effects of acetylsalicylic acid and indomethacin in human whole blood: potential role of cyclooxygenase-2 inhibition.

The aim of the study was to characterize the in vitro effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of pro-inflammatory cytokines in a human whole blood assay. Whole blood samples were pre-incubated with acetylsalicylic acid, indomethacin, selective cyclooxygenase (COX)-1 inhibitor (SC-560), COX-2 inhibitor (NS-398) or prostaglandin E2 (PGE2) before stimulation with lipopolysaccharide (LPS). Pro-inflammatory and anti-inflammatory cytokines were determined directly at the cell level with the help of flow cytometry and/or in the plasma supernatant with the help of ELISA. High doses of acetylsalicylic acid were needed to inhibit pro-inflammatory cytokine production. In contrast, low-to-moderate doses induced a modestly enhanced production of pro-inflammatory cytokines. Moreover, indomethacin was demonstrated to increase the expression of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in a dose-dependent fashion. Upon addition of PGE2, however, LPS-induced IL-6 and TNF-alpha production was suppressed regardless of indomethacin presence. Interestingly, selective COX-2 inhibition (NS-398), but not selective COX-1 inhibition (SC-560), exerted a stimulatory effect on the expression of pro-inflammatory cytokines. These data emphasize that the immunomodulating effects of NSAIDs in whole blood are dose-dependent. Furthermore, the induction of pro-inflammatory cytokine expression by NSAIDs is potentially mediated by COX-2 inhibition. Although NSAIDs are successfully used in clinical practice for their net anti-inflammatory properties, our observations may contribute to the understanding of side effects induced by NSAIDs and selective COX-2 inhibitors.

Adjuvants, Immunologic↗