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Biomedical subjects

S Walter

Publications and source records attributed to S Walter.

At least 55 records · Page 3Linked to original sources
PubMed2001

Antibiotic use in Ontario facilities that provide chronic care.

OBJECTIVE: To determine the incidence and variability of antibiotic use in facilities which provide chronic care and to determine how often clinical criteria for infection are met when antibiotics are prescribed in these facilities. DESIGN: A prospective, 12-month, observational cohort study. SETTING: Twenty-two facilities which provide chronic care in southwestern Ontario. PARTICIPANTS: Patients who were treated with systemic antibiotics over the study period. MEASUREMENTS: Characteristics of antibiotic prescriptions (name, dose, duration, and indication) and clinical features of randomly selected patients who were treated with antibiotics. RESULTS: A total of 9,373 courses of antibiotics were prescribed for 2,408 patients (66% of all patients in study facilities). The incidence of antibiotic prescriptions in the facilities ranged from 2.9 to 13.9 antibiotic courses per 1,000 patient-days. Thirty-six percent of antibiotics were prescribed for respiratory tract infections, 33% for urinary infections, and 13% for skin and soft tissue infections. Standardized surveillance definitions of infection were met in 49% of the 1,602 randomly selected patients who were prescribed antibiotics. Diagnostic criteria for respiratory, urinary, and skin infection were met in 58%, 28%, and 65% of prescriptions, respectively. One third of antibiotic prescriptions for a urinary indication were for asymptomatic bacteriuria. Adverse reactions were noted in 6% of prescriptions for respiratory and urinary infections and 4% of prescriptions for skin infection. CONCLUSIONS: Antibiotic use is frequent and highly variable amongst patients who receive chronic care. Reducing antibiotic prescriptions for asymptomatic bacteriuria represents an important way to optimize antibiotic use in this population.

Aged↗
PubMed2001

Ultrasonographic femur-tibial length ratio: a marker of Down syndrome from the late second trimester.

An observational prospective study reported that newborn babies with Down syndrome (DS) had short upper limbs that reach up to their pelvis. The shortening was most marked in the forearm (the middle segment of the upper limb) and this relative shortening resulted in an alteration of the proximal to middle segment length ratio. This study assumes that there is a similar alteration in the ratio of the lower limb. We propose to study the proximal to middle segment ratio in the lower limb in normal fetuses at different gestational ages. Against these norms we propose to study the ratio in fetuses with DS to see at what stage in intrauterine life the altered ratio becomes evident. We also propose to take postnatal measurements of upper and middle segments of both upper and lower limbs of babies born with DS and compare them with normal babies. Fetal femoral and tibial lengths were measured by routine antenatal ultrasound scans at a General hospital with 6000 deliveries a year. All babies delivered were examined for phenotypical evidence of DS. The in utero measurements recorded of babies born with DS were compared with the measurements in normal babies. Postnatal measurements of the arm and forearm, and the thigh and leg of babies with DS were taken soon after birth. These were compared with a control group of 20 consecutive normal babies born over 2 days. There were 3690 readings of 3075 normal fetuses and 8 measurements of 7 Down fetuses. The leg, the upper arm, and arm of newborns with DS were significantly shorter than controls (p<0.01). The upper limb reached up to the pelvis in infants with DS and not up to mid thigh as in normal babies. The forearm was shorter than the arm in infants with DS. This is a reversal of the ratio seen in controls. The ratio of femoral to tibial length remains near constant at 1.1 after 13 weeks' gestation in normal fetuses. It rises from 1.2 to 1.4 from 22 weeks' to 38 weeks' gestation in fetuses with DS. The mean standard deviation score of fetuses with DS was 4.53 compared with norms (SD 1.7, p<0.01). Conclusions of this study are: (1) short upper limbs (reaching only up to the pelvis) is a clinical feature of DS at birth; and (2) after 20 weeks' gestation, the ratio of femoral-tibial length can be a marker of DS in utero.

Adult↗
PubMed2001

Ophthalmodynamometry: a reliable method for measuring intracranial pressure.

Under physiological conditions, the pressure in the central retinal vein is equal to or higher than the intracranial pressure (ICP) because the cerebrospinal fluid (CSF) passes the sheath of the optic nerve before draining into the cavernous sinus. The optic nerve sheath is where the ICP affects the retinal venous pressure. Ophthalmodynamometry (ODM) is a useful method for determining the central retinal artery pressure. While papilledema and a lack of venous pulsations are commonly used as a vague indication of the ICP, ODM may be advantageous for determining the pressure in the central retinal vein. Until now, however, the venous pressure has never been compared with the intracranial pressure. In the present study, the pressure in the central retinal vein was recorded in 31 patients while the ICP was simultaneously being recorded for various reasons. The results demonstrate a linear correlation (r = 0.968) between the pressure in the central retinal vein and the ICP. This correlation is of great practical value since until now, reliable intracranial pressure monitoring has only been possible by invasive means, by placing a probe either in the brain parenchyma or the ventricle. Ophthalmodynamometry is useful for momentary assessment of the ICP, can easily be repeated, and may be used whenever an elevated ICP is suspected in hydrocephalus, brain tumors and after head injury. However, it is not suitable for continuous ICP monitoring.

Adolescent↗
PubMed2001

Polycythemia rubra vera versus secondary polycythemias. A clinicopathological evaluation of distinctive features in 199 patients.

To determine parameters of distinctive value in polycythemia rubra vera (PV) versus secondary polycythemias (SP), a clinicopathological study was performed on 199 patients. These presented with a borderline to marked elevation of the hemoglobin level (> 18 g/dl in men and > 16 g/dl in women). Evaluations of clinical features and bone marrow histopathology were carried out independently. According to the results derived from laboratory data and representative pretreatment trephine biopsies, three groups of patients emerged: group I presenting with the concordant clinical and morphological findings of early to manifest PV (136 patients), group II consisting of 55 patients with the congruent signs and symptoms of SP mostly caused by various chronic bronchopulmonal disorders, and finally eight patients (group III) with divergent findings. Between group I and II patients (PV versus SP), a number of clinical parameters proved to be significantly different. With the exception, of the red cell mass, platelet count, leukocyte alkaline phosphatase, LDH, spleen size, and the erythropoietin level had a significantly discriminating impact. Morphological features of distinctive value consisted of a set of specific lesions. Contrasting SP with an only borderline to slight increase in cellularity associated with a moderate enlargement of the erythroblastic islets, PV was always characterized by a significant increase in hematopoiesis, revealing a trilinear proliferation (panmyelosis). Megakaryopoiesis was strikingly different in PV as compared to SP by displaying clustering and a pleomorphous appearance. i.e., very small and giant megakaryocytes with staghorn-like nuclei were neighboring each other. Moreover, conspicuous alterations of the interstitial compartment were recognizable in SP. These consisted of deposits of cell debris in histiocytic reticular cells, iron-laden macrophages, and a plasmacytosis, implying an inflammatory reaction. These changes were only very rarely observed in PV, as opposed to a minimal to slight increase in reticulin fibers in about 12% of patients. In conclusion, a more elaborate evaluation of bone marrow features resulted in a set of diagnostic criteria with discriminating capacity that should be considered in prospective clinical trials.

Bone Marrow↗
PubMed2001

Influence of liposomal amphotericin B on CD8 T-cell function.

Liposomal amphotericin B was immunosuppressive on target cell lysis in vitro and on protection mediated by cytotoxic CD8 T cells in murine listeriosis. When dosages usually used for therapy in humans were compared, the immunosuppressive effect of 5 mg of liposomal amphotericin B/kg of body weight/day was similar to that of standard amphotericin B at 1 mg/kg/day, but a dosage of liposomal amphotericin B of 1 mg/kg/day was not suppressive in vivo.

Amphotericin B↗
PubMed2001

CT-based navigation systems for intraoperative radiotherapy using the afterloading-flab technique.

INTRODUCTION: The fact that conventional intraoperative radiotherapy does not give the opportunity to exactly document the radiation volume applied and the dose distribution has been criticized in many ways. We would like to introduce a system for surgical navigation and documentation of flap positioning in intraoperative brachytherapy using the afterloading flap technique. METHODS: Our system consists of an electromagnetic 3D-digitizer and a PC workstation. Spiral CT scans of the tumor region taken preoperatively are used for navigation and documentation of flap positioning, analogous to the procedure in neuronavigation. Registration is done via an external reference system which is attached to the iliac bone of the patient. RESULTS: The mean accuracy of digitalization of the 100 spheres in a pelvis model is about 2.6 +/- 0.5 to 3.7 +/- 9.9 mm. The mean navigation accuracy is 2.4 +/- 0.8 to 3.3 +/- 0.8 mm. These figures correspond to the clinical experience of our surgeons. DISCUSSION: The optimization of flab positioning by CT-guided navigation and the more accurate documentation of the dose volume and distribution in the patient is an important step on the way to improving the quality of individual radiation therapy. We are of the opinion that surgical navigation in the pelvic region should be subject to additional investigation in order to optimize the procedure.

Brachytherapy↗
PubMed2001

Lower concentration of thalamic n-acetylaspartate in patients with schizophrenia: a replication study.

OBJECTIVE: Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia. METHOD: The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined. RESULTS: Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found. CONCLUSIONS: There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.

Adult↗
PubMed2001

Aggregation-Dependent interaction of the Alzheimer's beta-amyloid and microglia.

Chronic glial activation possibly plays a role in chronic neurodegeneration in Alzheimer's disease (AD). It has been shown that amyloid peptide is capable of activating microglial cells in vitro. The aim of this study was to further characterize the structural preconditions for amyloid peptide in order to activate glial cells and to investigate whether this peptide is also able to induce glial activation in the living brain. We observed that amyloid peptide induced strong cellular activation in primary microglial cell culture as detected by the release of stable metabolites of nitric oxide (NO), when the peptide was fibrillar. For this activation, co-stimulation with interferon-gamma was a precondition. Using microdialysis of the living brain in a rat we observed pronounced NO generation when fibrillar amyloid peptide was stereotaxically injected. Non-fibrillar amyloid peptide did not induce such a glial reaction. No administration of interferon-gamma or any other co-stimulatory factor was necessary in vivo. Thus, we show that fibrillar, but not non-fibrillar amyloid peptide induced glial activation also in vivo. In the case of the living brain, the presence of deposits of fibrillar amyloid peptide could maintain a chronic microglial activation, ultimately leading to the progressive neurodegeneration associated with Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

Protein S-100B: a serum marker for ischemic and infectious injury of cerebral tissue.

The S-100B protein is released by injured astrocytes. After passage through a disintegrated blood-brain barrier (BBB) the molecule can be detected in the peripheral circulation. We investigated the association between the extent of brain injury and S-100B concentration in serum in cerebral injury caused by cerebral ischemia and cerebral fungal infection. Study I: The S-100B serum concentration was serially determined in 24 patients with ischemic stroke at 4, 8, 10, 24, 72 hours after the onset of symptoms. We observed that patients with brain lesions larger than 5 cm3 exhibited significantly increased serum levels of S-100B at 10, 24 and 72 hours compared to those with lesion volumes below 5 cm3. Furthermore, an association between S-100B serum concentration and neurological outcome was observed. Study II: In a mouse model of systemic fungal infection with Candida albicans we observed that serum levels of S-100B increased at day 1 after intravenous infection. At this time we could histologically demonstrate brain tissue injury by invading hyphae which had crossed the BBB. Furthermore, reactive astrogliosis was demonstrated by immunohistochemistry. On day 7 we found a significant decrease of S-100B serum level compared to day 1 and 4. This was associated with a demarcation of the fungi with leukocytes in brain tissue at this late phase of infection. No further invasion through the BBB was seen on day 7. In conclusion, serum levels of S-100B reflect the time course of tissue injury in cerebral ischemia and cerebral infection to a similar extent. Thus, S-100B may be a useful marker to assess cerebral tissue injury.

Adult↗
PubMed2001

Source of endothelin-1 in subarachnoid hemorrhage.

Endothelin-1 is the most potent vasoconstrictor known to date. This peptide is believed to play a pathophysiological role in the development of vasospasm, the most important complication of subarachnoid hemorrhage (SAH). In the present study we investigated the release of endothelin-1 in SAH and analyzed the cellular source of this peptide. At a protein and mRNA level we were able to show that endothelin-1 is produced by mononuclear leukocytes. Complementary in vitro studies revealed that aging and subsequent hemolysis of blood is sufficient to induce production of endothelin-1 by mononuclear leukocytes. Thus, cerebrospinal fluid-derived mononuclear leukocytes are a source of endothelin-1 in patients suffering from SAH. This finding may have important therapeutic implications as anti-leukocyte strategies could prevent cerebrovascular complications in SAH patients.

Adult↗
PubMed2001

Homocysteine in cerebrovascular disease: an independent risk factor for subcortical vascular encephalopathy.

Hyperhomocysteinemia is a risk factor for obstructive large-vessel disease. Here, we studied plasma concentrations of homocysteine and vitamins in patients suffering from subcortical vascular encephalopathy (SVE), a cerebral small-vessel disease leading to dementia. These results were compared to the homocysteine and vitamin plasma concentrations from patients with cerebral large vessel disease and healthy control subjects. Plasma concentrations of homocysteine, vascular risk factors and vitamin status (B6, B12, folate) were determined in 82 patients with subcortical vascular encephalopathy, in 144 patients with cerebral large-vessel disease and in 102 control subjects. Patients with SVE, but not those with cerebral large-vessel disease, exhibited pathologically increased homocysteine concentrations in comparison with control subjects without cerebrovascular disease. Patients with SVE also showed lower vitamin B6 values in comparison to subjects without cerebrovascular disease. Logistic regression analysis showed that homocysteine is associated with the highest risk for SVE (odds ratio 5.7; CI 2.5-12.9) in comparison to other vascular risk factors such as hypertension, age and smoking. These observations indicate that hyperhomocysteinemia is a strong independent risk factor for SVE.

Aged↗
PubMed2000

LINE L1 retrotransposable element is targeted during the initial stages of apoptotic DNA fragmentation.

Using a directional cloning strategy, DNA sequence information was obtained corresponding to the site of early radiation-induced apoptotic DNA fragmentation within the human lymphoblastoid cell line TK6. Data were obtained from 88 distinct clones comprising approximately 65 kbp of sequenced material. Analysis of all cloned material showed that sequences in the 10 bp immediately adjacent to the cleavage sites were enriched in short oligoT tracts. The proportion of repetitive DNA within the entire cloned material was found to be within the normal range. However the distribution of Alu and LINE repetitive DNA were biased to positions at or adjacent to the apoptotic cleavage site. In particular, a non-random distribution of five cleavage sites was found clustered within the second ORF of the LINE L1 that partially overlapped with two binding sites for the nuclear matrix-associated protein SATB1. Three other clones, containing alpha satellite elements, were also linked to a DNA matrix binding function. These data indicate that the site of chromatin loop formation at the nuclear matrix may be a specific target for early DNA fragmentation events during apoptosis.

Apoptosis↗
PubMed2000

Reconstruction and navigation system for intraoperative brachytherapy using the flab technique for colorectal tumor bed irradiation.

PURPOSE: To present the development of a new navigation and reconstruction system based on an electromagnetic free-hand tracker and on CT imaging for treatment planning of intraoperative high-dose-rate brachytherapy (IORT-HDRB) in the sacral region. Our aim is to improve accuracy and to enable individualized treatment planning and dose documentation to be performed for IORT-HDRB using a flab technique. METHODS AND MATERIALS: The material consists of an electromagnetic 3D tracker system, a PC workstation with Microsoft Windows NT 4.0 operating system, and a recognition program for continuous speech. In addition, we designed an external reference system constructed of titanium and Perspex, which is positioned in the pelvis, and a special digitizer pen for reconstruction of the flab geometry. The flab design incorporates a series of silicon 10-mm-diameter spherical pellets. Measurements were made with a pelvic phantom in order to study the accuracy of the system. The reconstruction results are stored and can be exported via network or floppy to our different treatment planning systems. RESULTS: Our results for the reconstruction of a flab with six catheters and a total of 100 spherical pellets give mean errors in the range (2.5 +/- 0.6) mm to (3.5 +/- 0.8) mm depending on the positions of the pelvic phantom and transmitter relative to the operation table. These errors are calculated by comparing the reconstruction results of our system with those using a CT-based reconstruction of the flab geometry. For the accuracy of the navigation system for the pelvic phantom, we obtained mean errors in the range (2.2 +/- 0.7) mm to (3. 1 +/- 1.0) mm. CONCLUSIONS: The new system we have developed enables navigation and reconstruction within the surgical environment with a clinically acceptable level of accuracy. It offers the possibility of individualized treatment planning and effective documentation of the 3D dose distribution in IORT-HDRB using a flab technique.

Brachytherapy↗
PubMed2000

Cytoplasmic localization of the interferon-inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200-gene family.

While interferons (IFNs) (alpha, beta and gamma), a family of cytokines, have the ability to exert the growth-inhibitory effect on target cells, the molecular mechanism(s) by which IFNs inhibit cell growth remains to be identified. Because IFN-inducible 'effector' proteins mediate the biological activities of IFNs, characterization of IFN-inducible proteins is critical to identify their functional role in IFN action. One family (the 200-family) of IFN-inducible proteins is encoded by structurally related murine (Ifi202a, Ifi202b, Ifi203, Ifi204 and D3) and human (IFI16, MNDA and AIM2) genes. The proteins encoded by genes in the family share a unique repeat of 200-amino acids and are primarily nuclear. The AIM2 gene is a newly identified gene that is not expressed in a human melanoma cell line. Here we report that AIM2 is estimated to be a 39 kDa protein and, unlike other proteins in the family, is localized primarily in the cytoplasm. Interestingly, overexpression of AIM2 in transfected cells retards proliferation and, under reduced serum conditions, increases the susceptibility to cell death. Moreover, AIM2 can heterodimerize with p202 in vitro. Together, these observations provide support to the idea that AIM2 may be an important mediator of IFN action.

Amino Acid Sequence↗
PubMed2000

Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia.

The authors performed a MRSI study of the anterior cingulate gyrus in 19 schizophrenic patients under stable medication and 16 controls in order to corroborate previous findings of reduced NAA in the anterior cingulate region in schizophrenia. Furthermore, correlations between NAA in the anterior cingulate gyrus and age or illness duration have been determined. A decreased NAA signal was found in the anterior cingulate gyrus of patients compared to controls. Subdividing the patient group into two groups depending on medication revealed that the group of patients receiving a typical neuroleptic medication showed a lower mean NAA in comparison to the group of patients receiving atypical antipsychotic drugs. No significant group differences in the creatine and phosphocreatine signal or the signal from choline-containing compounds were found. The NAA signal significantly correlated with age, and therefore, individual NAA values were corrected for the age effect found in the control group. The age-corrected NAA signal in schizophrenia correlated significantly with the duration of illness. The detected correlations of NAA decrease with age and illness duration are consistent with recent imaging studies where progressing cortical atrophy in schizophrenia was found. Further studies will be needed to corroborate a possible favorable effect of atypical antipsychotics on the NAA signal.

Adult↗