Biomedical subjects

C Leonard

Publications and source records attributed to C Leonard.

At least 37 records · Page 2Linked to original sources

PubMed1998

A phase I study of daily carboplatin and simultaneous accelerated, hyperfractionated chest irradiation in patients with regionally inoperable non-small cell lung cancer.

PURPOSE: This Phase I study was designed to determine the maximally tolerated dose (MTD) of daily low dose carboplatin with concurrent accelerated hyperfractionated radiotherapy (AHFX) in patients with locally advanced non-small-cell lung cancer. Patients also received consolidation chemotherapy with carboplatin. Secondary objectives were to determine the response rate, response duration, sites of first relapse, and survival. METHODS AND MATERIALS: Thirty patients received daily carboplatin at doses of 25 or 30 mg/m2. Concurrent radiotherapy was given in 1.5 Gy fractions twice daily for a total dose of 60 Gy. Following chemoradiotherapy, patients received four cycles of carboplatin at 350 mg/m2. RESULTS: Grade 4 esophagitis developed in 2 of 6 (33%) patients receiving 30 mg/m2 of daily carboplatin and was dose limiting. The remaining 24 patients received carboplatin at 25 mg/m2, with 3 patients developing Grade 4 esophagitis (13%). One of 22 patients who received consolidation carboplatin developed Grade 4 thrombocytopenia. An objective response was observed in 70% of patients (2 complete and 17 partial). Sites of failure were local (7 patients), distant (7 patients), and both (3 patients). The median time to progression was 8.3 months, with a median survival time of 18.3 months. The 1- and 2-year survival rates were 63 and 49%, respectively. CONCLUSIONS: Esophagitis was dose limiting when 30 mg/m2 of daily carboplatin was administered with AHFX. At the MTD of 25 mg/m2 of daily carboplatin plus AHFX followed by four cycles of carboplatin, the regimen was shown to be safe and as active or more active than other regimens. Thus, further studies with this regimen are warranted.

Adult↗

PubMed1998

Non-Hodgkin's lymphomas and myeloid disorders: deletions associated with t(2;5) and t(3;5) detected by FISH.

The nucleophosmin (NPM) gene is involved in two recurrent translocations in hematological malignancies: t(2;5) (p23;q35) in anaplastic large cell lymphoma (ALCL) and t(3;5)(q25.1;q34-35) in myelodysplasia and acute non-lymphocytic leukemia (ANLL). Using eight YACs encompassing the 5q34-q35 region, we could easily detect these two translocations. In both types of translocation, probable unexpected deletions were also discovered downstream of the breakpoint at 5q35.

Adolescent↗

PubMed1998

Dysregulation of monocyte differentiation in asthmatic subjects is reversed by IL-10.

BACKGROUND: IL-10 can modulate the differentiation of normal monocytes to macrophages, increasing the proportion of maturing cells with a phenotype consistent with T cell suppressive activity. Analysis of the immunopathology in endobronchial biopsies from asthmatic subjects has revealed significantly reduced proportions of suppressive macrophage populations associated with chronic T-cell mediated inflammation. OBJECTIVE: This study investigates whether the altered homeostasis within the lung macrophage populations in asthma is reflected in aberrant differentiation of peripheral blood monocytes and whether this differentiation may be influenced by IL-10. METHODS: Monocytes from 14 normal individuals and 14 atopic asthmatics were grown in culture for 7 days in the presence or absence of IL-10, added on day 5. Double immunofluoresence studies were performed on cytospins of the differentiated macrophages using the monoclonal antibodies RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. HLADR expression was quantified using the monoclonal antibody RFDR1. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring TNFalpha and TGFbeta production. RESULTS: With no cytokine addition the proportion of maturing macrophages with a suppressive phenotype (D1+D7+) at day 7 was lower in the asthmatic samples (18%) compared with normals (25%). IL-10 increased the proportion of suppressive cells in cultures of both asthmatic and normal monocytes with the increase in the asthmatic subjects (94% increase) being significantly greater than that in normal subjects (32% increase) (P<0.01). Asthmatic monocytes had a greater effect in stimulating MLR than normals (P < 0.05) but the addition of IL-10 reduced T cell proliferation in an MLR to a equivalent level in both groups. CONCLUSIONS: These results suggest that a fundamental problem may exist in the differentiation of monocytes in asthma which may be reversed by IL-10.

Adolescent↗

PubMed1998

Grip strengths and required forces in accessing everyday containers in a normal population.

OBJECTIVE: A commonly adhered to operating principle in occupational therapy clinics is that a person must exhibit 20 lb of grip strength before his or her hand is considered "functional." This study examined the relationship between hand and finger grip performances with the forces required to open common household containers. METHOD: The grip and pinch strengths of 49 college students were obtained using dynamometry. The forces required to open six common household containers were measured using Force Sensing Resistors attached to each container. RESULTS: Weak correlations were found (r = -.179 to r = .333) between grip and pinch strength performances and the forces used to operate the accessing mechanisms of the containers. Analyses of variances demonstrated significantly greater grip and pinch strength performances in men than in women (ps < .05) but no significant difference between the genders in the forces generated to open the containers (ps > .05). CONCLUSIONS: In a normal population of college students, the premise that greater hand strength affords greater performance in accessing everyday household containers was not supported. Implications suggest that grip and pinch dynamometry are not conclusive evaluative tools for predicting hand function while opening a select group of containers. The relationship between traditional dynamometry and hand performance during a variety of functional tasks needs to be examined in clinical populations as well.

Activities of Daily Living↗

PubMed1997

Allergen-induced CD30 expression on T cells of atopic asthmatics.

BACKGROUND: The importance of TH2-type T cell cytokines in atopic disease is widely accepted. CD30, a member of the TNF/NGF receptor superfamily, is expressed on a proportion of activated CD45RO+ T cells and has been proposed as a marker for TH2 phenotype. CD30 ligand-CD30 interaction has been shown to positively influence development of the TH2 phenotype, and serum levels of soluble CD30 (sCD30) have been used as prognostic markers in HIV, SLE, Epstein-Barr Virus infection and Hodgkin's Lymphoma but not as yet in allergic disease. OBJECTIVES: To establish if serum levels of sCD30 are elevated in atopic asthma and determine whether allergen-induced proliferation/activation of PBMCs from atopic asthmatics promotes CD30 expression on CD4+ T lymphocytes. Further, to determine if expression of CD30 and sCD30 correlate with disease severity. METHODS: Eighteen atopic asthmatics were each assigned a symptomatic disease score based on symptoms and bronchodilator rescue usage. Serum sCD30 was measured in peripheral blood by ELISA. PBMCs from atopic asthmatics were analysed with flow cytometry to obtain the proportions of CD4+ T cells expressing CD45RO and CD30. The cells were then cultured for 10 days with IL-2 with or without house dust mite antigen. A proliferation index was recorded and expression of CD30 and CD45RO retested. As a control, stimulation with PHA was used. Results with patients' PBMCs were compared with results of a parallel analysis of PBMCs from non-atopic healthy controls. RESULTS: Serum sCD30 was elevated in the 18 atopic asthmatics compared with a group of normal subjects but levels did not correlate with symptomatic disease activity. CD4CD45RO expression was low (14%) in atopic asthmatic peripheral blood but increased to 41% after 10 days culture with allergen. The CD4:CD8 ratio increased after Der p stimulation. A significant rise in the percentage of CD4+ T cells expressing surface CD30 (29%) was seen along with increased mean fluorescence intensity. Both these results correlated with symptomatic disease severity score. Non-specific PHA stimulation failed to significantly affect CD30 expression. CONCLUSIONS: There is a specific response to allergen in atopic asthma which causes significant increases in CD30 expression. This may correlate with disease severity.

Adolescent↗

PubMed1997

T-cell cytokines may control the balance of functionally distinct macrophage populations.

As monocytes differentiate into mature macrophages, subsets emerge that exhibit stimulatory, suppressive or phagocytic potential. These functionally distinct subsets can be discriminated using monoclonal antibodies RFD1 and RFD7. As examples of all these subsets have been repeatedly identified within the macrophage pool in a variety of organs the overall functional capacity of this pool will depend on the relative balance of these subpopulations. This study investigates whether this balance present in mature macrophage populations can be regulated by the local influence of T-cell-derived cytokines. The dose-dependent effect of cytokines interferon-gamma (IFN-gamma), interleukins (IL) IL-2, IL-4 and IL-10 on the phenotype and function of monocyte-derived macrophages was determined. Subsets of mature cells were quantified by identifying RFD1- RFD7- stimulatory cells (D1+); RFD1- RFD7+ phagocytes (D7+) and RFD1+ RFD7+ suppressive cells (D1 D7+). IFN-gamma and IL-4 increased the relative proportions of D1+ stimulatory cells and upregulated HLA-DR expression. IFN-gamma also increased the capacity of the mature macrophage pool to stimulate T-cell proliferation. IL-10 reduced the proportions of D1+ stimulatory cells while promoting the differentiation of D7+ phagocytes and D1/D7+ suppressive cells. IL-10 induced changes also reduced the functional capacity of the mature populations to stimulate T cells in auto and allogenic mixed lymphocyte reactions (MLR). IL-2 had no effect on differentiation of monocytes. Thus IL-4 and IFN-gamma are seen to induce the development of stimulatory macrophages while IL-10 promotes differentiation of monocytes to mature phagocytes and suppressive macrophages. It is concluded that mature macrophage phenotype is 'plastic' and under the control of T-cell-derived mediators. Furthermore, within the differentiating monocytes, phenotypic change appears to carry with it functional change, thus retaining the relationship between antigen expression and activity in the mature macrophage populations.

Adult↗

PubMed1997

Effect of the introduction of a financial incentive for fee-paying A&E attenders to consult their general practitioner before attending the A&E department.

BACKGROUND: The Health (Out-Patient Charges) Regulations 1994 were designed to encourage those Irish patients liable for their own health care costs to attend their GP before their local Accident and Emergency (A&E) department. Such patients are referred to as General Medical Services (GMS)-ineligible. Prior to the introduction of the regulations in March 1994, there was a perverse financial incentive for these patients to attend directly A&E departments instead of their GP. OBJECTIVE: The aim was to compare the number of GMS-ineligible patients referred by a GP during the year before and the year after the implementation of the Regulations. METHOD: This study involved the audit of all new attendances to a large A&E department, for 1 year before and after the introduction of the new regulations. The main outcome measures were the number of new attenders in the subsequent year, the proportion of GMS-ineligible attenders, the proportion of GMS-ineligible attenders referred by a GP and the proportion of GMS-ineligible attenders referred by a GP and categorized as having neither critical nor urgent complaints. RESULTS: The total number of new attenders in the year subsequent to the introduction of the regulations was 45,302, an increase of 4.9% on the previous year's total. The proportion of GMS-ineligible attenders decreased from 45.3 to 44% (-1.3%; 95% confidence interval (CI) -0.6 to -1.9). The proportion of GMS-ineligible attenders who were referred by a GP increased by 2.4% (95%; CI 1.7-3.1). The proportion of GMS-ineligible attenders, referred by a GP with complaints categorized as neither critical nor urgent, increased by 2.5% (95%; CI 1.8-3.2). CONCLUSIONS: The introduction of the regulations was associated with a small, but statistically significant, reduction in the number of GMS-ineligible patients who attended with non-emergency conditions. The proportion of GMS-ineligible attenders who were referred by a GP increased by 2.4% (95%; CI 1.7-3.1). The overall workload of the A&E department was, however, unaffected. Further evaluation of the effects of this reduction on the health status of patients is required.

Adult↗

PubMed1997

"Golf ball liver": agent orange hepatitis.

2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective weedkiller which works by uncoupling oxidative phosphorylation and is in widespread use. It is known as "agent orange". A 65 year old man had acute hepatitis, thought to be caused by exposure to 2,4-D. The patient ingested 2,4-D as a result of habitual licking of his golf ball. Clinical and histological data together with a challenge test confirmed the diagnosis of "golf ball liver".

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed1997

Urea inhibits inducible nitric oxide synthase in macrophage cell line.

Macrophage dysfunction is considered an important contributory factor for increased propensity of infections in uremia. Because nitric oxide (NO) is believed to be an effector molecule of macrophage cytotoxicity, we propose that the dysfunction may be related to impaired NO synthesis. To verify this hypothesis, we evaluated macrophage NO synthesis in the presence of urea, a compound that accumulates in renal failure and is believed by some to be a uremic toxin. Macrophages (RAW 264.7 cells) were incubated with bacterial lipopolysaccharide to induce NO synthesis, whereas the test groups had various concentrations of urea in addition. NO synthesis was measured by assaying the supernatant for nitrites and nitrates by chemiluminescence. We observed that urea consistently produced a dose-dependent reversible inhibition of inducible NO production in macrophages, whereas parathormone, another toxin retained in uremia, had no such inhibitory effects. Further studies revealed that mRNA for inducible NO synthase was not inhibited by urea. We thus conclude that urea inhibits inducible NO synthesis in macrophages by a posttranscriptional mechanism and that this may be important in macrophage dysfunction of uremia.

Animals↗

PubMed1997

Allergen-induced cytokine production in atopic disease and its relationship to disease severity.

The Th2 cytokines, interleukin (IL)-4 and IL-5, have an important role in atopic disease. CD30 is a transmembrane molecule that may be expressed on a proportion of activated T-lymphocytes and has been reported to be a marker for Th2 phenotype. Our objective was to compare the in vitro cytokine responses and CD30 expression of peripheral blood mononuclear cells (PBMCs) to stimulation with house dust mite antigen (Dermatophagoides pteronyssinus) in atopic asthmatics, atopic nonasthmatics, and normal subjects, and to see if atopic asthmatic cytokine production correlated with symptomatic disease activity and whether cytokine production was allergen-specific. Eighteen atopic asthmatics (all were allocated a symptomatic disease score), 6 atopic nonasthmatics, and 7 healthy nonatopic individuals were studied. Resting serum IL-4 levels were measured, then PBMCs were separated using Lymphoprep density centrifugation and cultured in modified RPMI 1640 medium. PBMCs were stimulated with IL-2 alone or with D. pteronyssinus (1,000 subcutaneous units/ml) with IL-2 and harvested after 5 and 10 d. Using monoclonal antibodies and flow cytometry we obtained the percentage of CD4+ T cells expressing CD30 and the intensity of CD30 staining. Culture supernatants were analyzed for IL-4 and interferon gamma (IFN-gamma) using an enzyme-linked immunosorbent assay. In 9 atopic asthmatics PBMCs were also stimulated nonspecifically using phytohemagglutinin (PHA). IL-4 was detectable in the serum of atopic subjects but not in normal subjects. Stimulation of PBMCs with D. pteronyssinus produced significant amounts of IL-4 in atopic asthmatics and atopic nonasthmatics, but minimal quantities in normal subjects. Much lower levels of IFN-gamma were produced by atopic asthmatics in response to D. pteronyssinus compared to atopic nonasthmatics. IFN-gamma levels had an inverse correlation with asthmatic symptom score. CD4+ T-cell expression of CD30 also correlated inversely with IFN-gamma production and IFN-gamma:IL-4 ratio. PHA produced minimal levels of IL-4 compared to specific allergen stimulation. It is concluded that different groups of atopic patients exhibit different patterns of allergen-induced cytokine production. In vitro allergen-induced cytokine production in atopic asthmatics correlated with symptomatic disease activity, and is allergen-specific.

Adolescent↗

PubMed1997

Lung immunopathology in cases of sudden asthma death.

The histopathology of airway inflammation in rare cases of sudden asphyxic asthma death (SAAD) is unclear. This study examines, for the first time, the relative disposition of lymphocyte and macrophage subsets and eosinophils in proximal and distal tissues of such cases. Multiple resection specimens from five cases of SAAD were studied. Tissue blocks were obtained at necroscopy and immediately frozen in liquid nitrogen within 18 hours of death (death occurring within 1 h of the onset of an unprovoked asphyxic asthma attack). After immunohistological staining, frozen sections underwent semi-quantitative analysis (cell counts per unit area) for T-cells, macrophages and eosinophils using computerized imaging systems. Subsets of T-cells and macrophages were estimated using double immunofluorescence techniques. Variability within samples, between samples and between cases was compared. These cases of fatal asthma showed infiltrates of T-cells, macrophages and eosinophils within peribronchial tissues. Distinct from stable asthma, a CD8+ T-cell dominance was found. A high proportion of eosinophils were activated (EG2+), whereas the relative proportion of antigen-presenting cells (RFD1+) did not seem to be abnormal, although numbers of these cells were high. These features were seen both in proximal and distal tissues. The variability of these parameters within an individual was 9.4-15.2%, however, the variability between individual cases was greater. Sudden asphyxic asthma is associated with inflammatory infiltrates both of proximal and distal lung tissues. In contrast to stable asthma, this infiltrate contains large numbers of CD8+ T-cells, suggesting distinct qualitative as well as quantitative characteristics in the immunopathology of sudden asthma death.

Acute Disease↗

PubMed1997

Bronchoscopic diagnosis of sarcoidosis.

Transbronchial lung biopsy (TBLB), transbronchial needle aspiration (TBNA) of mediastinal lymph nodes and bronchoalveolar lavage (BAL) are routinely performed at fibreoptic bronchoscopy. Up to the present time, no data have been available on the efficacy of performing all three of these procedures simultaneously in the bronchoscopic work-up of sarcoidosis. A prospective study was undertaken to compare the diagnostic yield from TBLB, TBNA and BAL in patients presenting with clinical and radiological features typical of sarcoidosis. Thirteen consecutive patients with clinical and radiological features consistent with stage I and II sarcoidosis underwent bronchoscopy with TBLB, TBNA and BAL. Noncaseating granulomata (stain and culture negative for tuberculosis bacilli and fungi) were found in seven of the 13 patients by TBLB, and in six of the 13 patients by TBNA (of which four patients had negative TBLB). Eight of the 13 patients had classical "sarcoid" BAL findings, i.e. >12% lymphocytes, and high CD4+:CD8+ lymphocyte ratio. Combining TBLB, TBNA and BAL gave a diagnostic sensitivity of 100% (12 out of 12 patients) for sarcoidosis. The remaining patient had nondiagnostic bronchoscopic studies and mediastinoscopy biopsy showed a non-Hodgkin's lymphoma. Our data suggest that performing simultaneous transbronchial lung biopsy, transbronchial needle aspiration and bronchoalveolar lavage produces optimal results in the diagnosis of sarcoidosis.

Biopsy, Needle↗

PubMed1996

NMR spectroscopy analysis of oligoguluronates and oligomannuronates prepared by acid or enzymatic hydrolysis of homopolymeric blocks of alginic acid. Application to the determination of the substrate specificity of Haliotis tuberculata alginate lyase.

The 1H and 13C NMR chemicals shifts of the various saturated and unsaturated timers obtained by acid or enzymatic depolymerisation of homopolymeric blocks of alginates are reported. In addition, 13C NMR chemical shifts are assigned for several saturated oligomers of higher polymerisation degrees. Breakdown of alginate and of homopolymeric alginate blocks by Haliotis tuberculata alginate lyase was monitored with 1H NMR spectroscopy and the signals relevant to the identification of the lyase products are pointed out. The enzymes performs beta-elimination on the mannuronic acid residues, independently of their immediately surrounding neighbours. Application of this approach to the analysis of the substrate specificity of alginate lyases is discussed.

Alginates↗

PubMed1996

Reductions in motoneuronal neurofilament synthesis by successive axotomies: a possible explanation for the conditioning lesion effect on axon regeneration.

Axons regenerate more rapidly after a test lesion if they received a conditioning lesion. Previous work suggests that the cell body reaction to injury is responsible for this conditioning lesion effect. Here we examined the effects of the second, test lesion on the expression of the major cytoskeletal proteins, tubulin, actin, and neurofilament proteins. Using 2D-SDS-PAGE to separate these cytoskeletal proteins synthesized in the facial nucleus, along with in situ hybridization and RNA blotting to measure corresponding mRNA levels, we found that previous conditioning had little effect on actin or tubulin responses to a test lesion, but resulted in further decrease in neurofilament synthesis. Immunocytochemistry and electron microscopy revealed a greater loss of neurofilaments from the proximal conditioned axons, and axonal shrinkage. We suggest that the reduction in neurofilaments in the proximal axons of conditioned neurons reduces interference with tubulin transport. This may allow more tubulin to be transported more rapidly into the growing axon, to support the faster elongation rate of conditioned axons following a test lesion.

Animals↗

PubMed1996

Intractable temporal lobe epilepsy: comparison of positron emission tomography with qualitative and quantitative MR.

PURPOSE: To compare the ability of qualitative fludeoxyglucose F 18 positron emission tomography (QPET), qualitative MR imaging (QMR), and quantitative MR imaging with hippocampal formation volumetric assessment (HV MR) to lateralize the seizure focus in patients with temporal lobe epilepsy. METHODS: Sixteen consecutive patients undergoing presurgical examination for temporal lobe seizures had QPET, QMR, and HV MR. The presence of temporal lobe epilepsy was confirmed by Engel class I or II outcomes at 1-year postoperative follow-up examinations. A QPET, QMR, or HV MR study was considered to be lateralizing if it matched the side of the seizure focus, nonlateralizing if it did not lateralize the seizure focus to either temporal lobe, or incorrectly lateralizing if it lateralized the seizure focus to the incorrect side. RESULTS: Of 16 patients with proved temporal lobe seizures, QPET was correctly lateralizing in nine (56%), nonlateralizing in six (37.5%), and incorrectly lateralizing in one (6%). QMR was correctly lateralizing in six (37.5%), nonlateralizing in six (37.5%), and incorrectly lateralizing in four (25%). HV MR was correctly lateralizing in all 16 patients (100%). Age at onset, seizure duration, and total number of seizures did not correlate with QPET, QMR, and HV MR lateralization. CONCLUSIONS: Our results show that each imaging technique yields useful information for seizure lateralization in temporal lobe epilepsy and that HV MR yields considerably more information that QPET or QMR.

Adolescent↗

PubMed1995

Measurement of lower limb blood flow in patients with neurogenic claudication using positron emission tomography.

STUDY DESIGN: Ten subjects (seven with neurogenic claudication and three control subjects) underwent examination of lower limb muscle blood flow before and after exercise using positron emission tomography. OBJECTIVES: To investigate the hypothesis that lower limb muscle ischemia was the origin of symptoms in neurogenic claudication. BACKGROUND: Patients with neurogenic claudication secondary to spinal stenosis experience lower limb discomfort after exercise similar to that of ischemic claudication. However, they do not have clinical evidence of peripheral vascular disease. The authors postulated that the lower limb discomfort in patients with neurogenic claudication may arise from muscle ischemia due to inadequate dilatation of arterioles in response to exercise, this itself arising secondary to sympathetic dysfunction due to spinal stenosis. METHOD: Using O15-labeled water and positron emission tomography measured thigh and leg muscle blood flow response to exercise bilaterally in seven patients with unilateral neurogenic claudication and three control subjects were measured. RESULTS: The average values obtained for mid-thigh and mid-calf muscle perfusion at rest were 2.57 ml/min/100 g tissue (2.23-3.90) and 2.39 ml/min/100 g tissue (2.03-3.46), respectively. The average values obtained from mid-thigh and mid-calf perfusion after exercise were 4.41 ml/min/100 g tissue (2.8-6.0) and 4.87 ml/min/100 g (2.2-11.7). We found no difference in muscle perfusion between symptomatic and asymptomatic limbs in this group of patients. CONCLUSION: These studies suggest that muscle ischemia is not the origin of symptoms in most patients with neurogenic claudication.

Adult↗

PubMed1995

Hippocampal volumetrics differentiate patients with temporal lobe epilepsy and extratemporal lobe epilepsy.

OBJECTIVE: To determine whether the occurrence of hippocampal formation (HF) volumetric asymmetry can reliably discriminate between complex partial seizures (CPSs) of a temporal lobe origin and CPSs of an extra-temporal lobe origin in a prospective study of patients with intractable CPSs (approximately 70% of patients have electrographic foci in the temporal lobe [HF volumetric asymmetry on magnetic resonance imaging scans has been shown to lateralize such foci reliably)]. DESIGN: We examined HF volumetrics on magnetic resonance imaging scans that were acquired with a 1-T magnetic resonance imaging scanner (Siemens Magnetom, Siemens Medical Systems, Iselin, NJ) by using magnetization-prepared rapid gradient echo three-dimensional sequences (producing a gapless series of high-contrast 1.25-mm images). These data were compared with ictal, interictal, invasive, and noninvasive videoelectroencephalographic monitoring data, functional imaging data, and outcome data to define each patient's type of epilepsy. SETTING AND PATIENTS: Forty-one patients were recruited from a tertiary university comprehensive epilepsy program, and 22 control subjects were recruited from the neurologically normal university community. RESULTS: Among the control subjects, the difference in HF volumetrics (right-left HF volumetrics) was + 0.085 +/- 0.253 cm3. Of the 41 patients, 25 had temporal lobe epilepsy. When we set the upper limit of normal at the mean +/- 3 SDs, all patients beyond the upper limit had CPSs of a temporal lobe origin. Of the patients with temporal lobe epilepsy, only three fell within normal limits. No patient with CPSs of an extratemporal lobe origin fell beyond the upper limit. CONCLUSION: The presence of significant HF volumetric asymmetry makes it highly unlikely that a patient's CPSs are of an extratemporal lobe origin.

Adolescent↗

PubMed1995

Resistance to glomerular injury in the diabetic biobreeding rat.

This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long-term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2-4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min-1 (100 g body weight)-1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end-product cross-links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end-products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11-fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2- and NO3- (24 h)-1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end-products.

Animals↗