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PubMed1998

Effects of a traumatic neocortical lesion on cerebral metabolism and gene expression of rats.

The effects of a traumatic neocortical lesion, induced by transcranial cold injury, on brain metabolism and gene expression were examined. The surrounding of the lesions was characterized by increased glucose and lactate levels without major disturbances of protein synthesis or energy state. A transient pH decrease by 0.4 units was noticed 1 h post-injury, which shifted towards alkaline values by 3 h. The metabolic disturbances did not differ between injured animals with spontaneous spreading depressions (SD, n = 14) and those without SD (n = 7). In SD animals, c-fos mRNA was strongly elevated in the injury-remote cortex, but hsp72 mRNA was not enhanced. Thus, in contrast to focal ischemia, the metabolic dysfunction around traumatic cortical lesions is not aggravated by SD.

Adenosine Triphosphate↗

PubMed2003

Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy.

BACKGROUND: Nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy provides sufficient conditions for progressive subcutaneous fat wasting in HIV-infected patients. As NRTI-induced host toxicity is proposed to involve cellular mitochondrial DNA (mtDNA) depletion, determinants of cellular mtDNA copy number and mitochondrial mass in adipocyte samples from NRTI-treated HIV-infected patients and antiretroviral-naive controls were investigated. Adipose tissue morphology was also assessed. METHODS: Subcutaneous fat samples were obtained from NRTI-treated, HIV-infected patients (n = 21), antiretroviral therapy-naive HIV-infected controls (n = 11), and HIV-seronegative controls (n = 6). Non-adipocytes were removed by collagenase digestion. Adipocyte mtDNA copies/cell was measured using a real time PCR-based assay, and adipocyte mitochondrial protein content was also measured. Light and electron microscopy were performed on tissue samples. FINDINGS: Adipocyte mtDNA copies/cell values were similar (P = 0.56) in HIV seronegative and HIV-infected control groups. NRTI treatment was associated with reduced adipocyte mtDNA copies/cell, representing mean mtDNA depletion in NRTI-treated individuals of 77.7% compared with the mean value for the HIV-infected control group (P < 0001). Additionally, significant differences were found in adipocyte mtDNA copies/cell between patients receiving stavudine (n = 12, mean mtDNA depletion 87.1%) and zidovudine (n = 9, mean mtDNA depletion 52.1%) (P < 0.001). Adipocyte mitochondrial mass was increased in the stavudine group only (mean increase 289%, P < 0.01). INTERPRETATION: NRTI therapy is associated with mtDNA depletion and mitochondrial proliferation in adipocytes, consistent with the hypothesis that NRTI-induced mtDNA depletion contributes to the pathogenesis of subcutaneous fat wasting. Morphologic assessment also supports a role for NRTI therapy in inducing adipocyte metabolic dysfunction and cell death.

Adipocytes↗

PubMed1981

The pathogenesis of primary internodal demyelination produced by acetyl ethyl tetramethyl tetralin: evidence for preserved Schwann cell somal function.

The pathogenesis of primary internodal PNS demyelination produced by acetyl ethyl tetramethyl tetralin (AETT) has been studied using subchronically intoxicated rats with intact sciatic nerves (right side), and with focally traumatized nerves (left side) undergoing myelin breakdown and repair. Sixteen Sprague-Dawley rats were given approximately 50 mg/kg/d of AETT, dissolved in ethanol and placed in food. Six age-matched control animals received daily an equivalent amount of food treated with the same volume of alcohol. After six weeks and prior to the onset of demyelination, AETT treatment had increased the number of visible Schmidt-Lanterman incisures per internode of large-diameter fibers in tibial nerves. By ten weeks, the same group of fibers had begun to develop juxtanodal and internodal myelin bubbles. Subsequently, intramyelinic phagocytes of hematogenous derivation removed entire internodes of edematous myelin. Schwann cell response to injury was studied in control and AETT-intoxicated animals which had undergone left hindlimb surgery 1 to 2 days after beginning toxin treatment: (a) a perineurial window was placed in the peroneal nerve to induce focal demyelination and remyelination, (b) the tibial nerve was transected between ligatures to study Wallerian degeneration of the distal stump, and (c) the sural nerve was focally crushed to induce axonal regeneration and myelination. Qualitatively similar responses to nerve injury were seen 1 to 16 weeks later in AETT-treated and control animals. These results are compatible with the view that AETT damages myelin directly, that Schwann cell somal functions are not seriously affected by AETT, and that Schmidt-Lanterman incisures undergo changes prior to demyelination, which may represent a physiological response of the Schwann cell to toxic attack on its myelin sheath. Taken in concern, these observations challenge the long-held view that primary internodal demyelination is necessarily indicative of metabolic dysfunction of the Schwann cell soma.

Animals↗

PubMed1996

Colocalization of lysosomal hydrolase and beta-amyloid in diffuse plaques of the cerebellum and striatum in Alzheimer's disease and Down's syndrome.

The lysosomal hydrolases, cathepsin D (Cat D) and beta-hexosaminidase A (HEX), which are normally intracellular enzymes, colocalize with beta-amyloid in a subgroup of diffuse plaques in the cerebellum and striatum of individuals with Alzheimer's disease or Down's syndrome. Using specific antisera in combination with single- and double-label immunocytochemical techniques, extracellular hydrolase was detected in 30 to 40% of the diffuse plaques in the cerebellar molecular layer and nearly all of the diffuse plaques in the striatum. In both Alzheimer's disease and Down's syndrome, about 5 to 10% of the cerebellar Purkinje cells contained abnormally increased numbers of hydrolase-positive lysosomes despite their normal appearance by conventional histologic stains. Occasional atrophic Purkinje cells identified by Nissl stain were intensely immunostained. By confocal imaging analysis, abnormal hydrolase-laden Purkinje cell dendrites were seen coursing through some hydrolase-positive plaques and were continuous with dendritic branches that terminated within deposits of extracellular hydrolase and beta-amyloid. In the striatum, intensely immunostained abnormal-appearing neurons were commonly associated with extracellular deposits of hydrolase immunoreactivity and beta-amyloid within diffuse plaques and in the less commonly seen classical plaques. In both brain regions, other hydrolase-negative beta-amyloid deposits were seen, these being associated with blood vessels. The presence of HEX immunoreactivity in neurons, but not in glia, and its abundance in plaques support earlier studies, suggesting that neurons are the principal source of plaque hydrolase. An endosomal-lysosomal system upregulation, with increased hydrolase expression and extracellular enzyme deposition in plaques, is, like beta-amyloid deposition, an early marker of metabolic dysfunction potentially related to primary etiologic events in Alzheimer's disease and Down's syndrome.

Adult↗

PubMed1986

Tests for hepatotoxicity: usefulness in screening workers.

General tests of hepatotoxicity must be selected to identify all seven different types of exposure effect--cytotoxicity, cholestasis, fibrosis, vascular injury, metabolic dysfunction, impairment of the reticuloendothelial system, and carcinogenesis--whereas specific tests need only identify one or more. The liver's multifunctional character requires using sets of tests that include blood, urine, breath, isotopic, sonic, radiological, histological, and genetic tests. In this paper, traditional studies (eg, enzymes, proteins) are reviewed for medical screening and biological monitoring for specificity, sensitivity, selectivity, and cost-effectiveness. Status of newer tests (eg, clearance, radioisotopic assay, scans) will be reviewed, and developing tests (eg, molecular, genetic) for occupational use will be introduced. Practical application of these tests will be reviewed regarding clinical evaluations, interpretation, and triage. Finally, the medical-socioeconomic implications at initial medical screening and during subsequent monitoring will be illustrated.

Breath Tests↗

PubMed2005

Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression.

OBJECTIVE: Heat shock protein (HSP) expression is vital to cellular and tissue protection after stress or injury. However, application of this powerful tool in human disease has been limited, as known enhancers of HSPs are toxic and not clinically relevant. Glutamine (GLN) can enhance HSP expression in non-clinically relevant animal injury models. The aim of this study was to assess the ability of GLN to enhance pulmonary HSP expression, attenuate lung injury, and improve survival after sepsis in the rat. DESIGN: Prospective, randomized, controlled animal trial. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: We utilized a rat model of cecal ligation and puncture to induce sepsis. GLN or saline was administered 1 hr after initiation of sepsis via single tail-vein injection. We analyzed heat shock factor-1 phosphorylation, HSP-70, and HSP-25 via Western blot. Tissue metabolism was assayed by magnetic resonance spectroscopy. Occurrence of lung injury was determined via histopathologic examination. An inhibitor of HSP expression, quercetin, was utilized to assess role of HSP expression in prevention of sepsis-related mortality. MEASUREMENTS AND MAIN RESULTS: GLN, given after initiation of sepsis, enhanced pulmonary heat shock factor-1 phosphorylation, HSP-70, HSP-25, and attenuated lung injury after sepsis. Further, GLN improved indices of lung tissue metabolic function (adenosine 5-triphosphate/adenosine 5-diphosphate ratio, nicotinamide adenine dinucleotide) after sepsis. No significant effect of GLN on lung tissue-reduced glutathione was observed. GLN treatment led to a significant decrease in mortality (33% [6 of 18] GLN-treated rats vs. 78% [14 of 17] saline-treated rats). Administration of the HSP inhibitor quercetin blocked GLN-mediated enhancement of HSP expression and abrogated GLN's survival benefit. CONCLUSIONS: GLN has been safely administered to critically ill patients and shown to improve outcome without clear understanding of the protective mechanism. Our results indicate GLN may prevent the occurrence of lung injury, lung tissue metabolic dysfunction, and mortality after sepsis via enhancement of deficient lung heat shock factor-1 phosphorylation/activation and HSP expression.

Analysis of Variance↗

PubMed2006

Vascular failure: A new clinical entity for vascular disease.

Atherosclerosis is characterized by the response of the vessel wall to chronic multifactorial injury leading to the formation of atheromatous or fibrous plaques. Endothelial dysfunction represents an initial stage of atherosclerosis. In addition to endothelial dysfunction, smooth muscle dysfunction, metabolic abnormalities of the vessel wall including inflammation, oxidative stress and alterations of neurohormonal balance occur in various stages of atherosclerosis. We now propose a new clinical entity 'vascular failure', defined as the integration of all of these vascular abnormalities. Vascular failure is not an anatomical disease, but rather a comprehensive syndrome of abnormal vascular function. Vascular failure extends from risk factors to established atherosclerotic disease with arterial stenosis, and further to calcification of the vessel wall or serious vascular events that may be caused by plaque rupture and thromboembolic occlusion. We propose aggressive intervention to modify various risk factors, applying to this integrated new entity, vascular failure.

Atherosclerosis↗

PubMed2005

Pathophysiology of peripheral muscle wasting in cardiac cachexia.

PURPOSE OF REVIEW: Many different mechanisms have been proposed to explain muscle wasting in patients with heart failure; however, the pathogenesis remains largely obscure. This manuscript looks at current developments concerning the pathophysiology of skeletal muscle wasting in cardiac cachexia. RECENT FINDINGS: Many studies have shown that malnutrition, malabsorption, metabolic dysfunction, anabolic/catabolic imbalance, inflammatory and neurohormonal activation, and cell death play an important role in the pathogenesis of wasting in cardiac cachexia. However, the aetiology of the muscle changes is not entirely clear. In biopsies of skeletal muscles from animals with cardiac cachexia increased rates of protein degradation have been observed, with increased activity of the ubiquitin-proteasome proteolytic pathway. Skeletal muscle apoptosis may also play a role in muscle atrophy and wasting and can be partly prevented by neurohormonal inhibition, but it has recently been reported that in cachectic patients with chronic heart failure apoptosis is not the main pathway of cell death and muscle loss. SUMMARY: Many hypotheses have been used to explain the pathogenesis of muscle wasting in cardiac cachexia. Cardiac cachexia is a multifactorial disorder, and the targeting of different pathways will be necessary for effective treatment. The immune and neurohormonal abnormalities present in chronic heart failure may play a significant role in the pathogenesis of the wasting process. It has been suggested that common pathogenetic mechanisms underlie the loss of muscle mass in different cachectic states. More studies are needed to show whether there is a common pathway in cardiac cachexia and the other cachectic states.

Apoptosis↗

PubMed2006

In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection.

BACKGROUND: Bioluminescence imaging (BLI) modalities are being developed to monitor islet transplant mass and function in vivo. The aim of this study was to use the BLI system to determine how the change in functional islet mass correlated to metabolic abnormalities during the course of alloimmune rejection in a murine transplant model. METHODS: Islets obtained from a transgenic mouse strain (FVB/NJ-luc) that constitutively expressed firefly luciferase were transplanted to various implantation sites of syngeneic wild-type FVB/NJ or allogeneic Balb/C streptozotocin-induced diabetic recipients. In vivo graft luminescent signals were repeatedly measured after transplantation using the BLI system and related to blood glucose levels and graft site histologic findings. RESULTS: The BLI signals were detected in as few as 10 islets implanted in the renal subcapsular space, intrahepatic, intraabdominal, and subcutaneous locations. There was a linear relationship between the number of islets transplanted and luminescence intensity. In isografts, stable luminescence intensity signals occurred within 2 weeks of transplantation and remained consistent on a long-term basis (18 months) after transplantation. In allografts, after normoglycemia was achieved and stable luminescence intensity occurred, graft bioluminescent intensity progressively decreased several days before permanent recurrence of hyperglycemia as a result of histologically proven rejection ensued. CONCLUSIONS: Bioluminescence imaging is a sensitive method for tracking the fate of islets after transplantation and is a useful method to detect early loss of functional islet mass caused by host immune responses even before overt metabolic dysfunction is evident. Bioluminescence imaging holds promise for use in designing and testing interventions to prolong islet graft survival.

Animals↗

PubMed2026

Two Genomes, one Outcome: Stratifying Donor and Recipient Polygenic Risk Score to Improve Kidney Allograft Longevity.

Kidney transplantation outcomes arise from complex interactions among donor organ quality, recipient susceptibility, and immunologic compatibility, yet conventional clinical risk models explain only a modest fraction of outcome variability. Polygenic risk scores (PRS) offer a promising framework to enhance transplant risk assessment by integrating genome-wide genetic information from both donor and recipient into biologically informed models. This narrative review examines the mechanistic basis for PRS application in kidney transplantation and variant clustering approaches that link polygenic signals to specific biological pathways underlying alloimmunity, fibrosis, and metabolic dysfunction. We compare current PRS construction methodologies, highlighting their respective strengths and limitations in transplant cohorts. Transplant PRS are distinguished from single-genome disease models by their capacity to capture dual-genome interactions, simultaneously quantifying inherited donor organ liability and recipient genetic susceptibility within an integrated framework. This dual-genome architecture requires novel risk stratification paradigms in which combined donor-recipient polygenic profiles inform pretransplant decision-making in ways that neither genome alone can achieve. However, current PRS contribute only incremental variance beyond established clinical predictors, and critical limitations persist, including European ancestry bias, small cohort sizes, incomplete replication, and undefined clinical actionability thresholds. We critically evaluate these implementation barriers and outline future directions for integrating dual-genome PRS with clinical, molecular, and environmental data. The longer-term goal is to advance precision kidney transplantation through applications such as donor selection, immunosuppression tailoring, and individualized posttransplant surveillance. Realizing this potential will require validation in adequately powered, ancestry diverse, prospective transplant cohorts.

Journal Article↗

PubMed2004

Terlipressin increased the concentration of L-lactate in the rectal lumen in a patient with septic shock.

Terlipressin--a long-acting analogue of vasopressin--has been described to restore blood pressure in patients with catecholamine-resistant septic shock without obvious complications. We administered low-dose terlipressin (a single i.v.-bolus of 0.5 mg) to a patient with severe, hyperdynamic septic shock requiring high dosage of noradrenalin. After terlipressin the dose of noradrenalin could be reduced by 2/3 to obtain the same blood pressure. Two hours after terlipressin, the cardiac index had decreased from 6.2 to 3.3 l min(-1) m(-2) and the concentration of L-lactate in the rectal lumen, as assessed by equilibrium dialysis, increased from 3.6 to 7.2 mmol l(-1). In contrast, the systemic concentration of L-lactate was unaffected around 2.8 mmol l(-1). After 8 h the effect of terlipressin started to decline, and after an additional 12 h the systemic haemodynamics, dose of noradrenalin and concentrations of rectal and systemic L-lactate were the same as prior to the administration of terlipressin. As a strong vasopressor, terlipressin may have further impaired the metabolic dysfunction in the rectal mucosa either directly via vasoconstriction of mucosal vessels or through decreased cardiac output in this patient with noradrenalin-treated septic shock.

Aged↗

PubMed2004

Metabolic changes of subcortical structures in intractable focal epilepsy.

PURPOSE: Intractable focal epilepsy is commonly associated with cortical glucose hypometabolism on interictal 2-deoxy-2[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET). However, subcortical brain structures also may show hypometabolism on PET and volume changes on magnetic resonance imaging (MRI) studies, and these are less well understood in terms of their pathophysiology and clinical significance. In the present study, we analyzed alterations of glucose metabolism in subcortical nuclei and hippocampus by using FDG-PET in young patients with intractable epilepsy. METHODS: Thirty-seven patients (mean age, 7.5 years; age range, 1-27 years) with intractable frontal (n = 23) and temporal (n = 14) lobe epilepsy underwent FDG-PET scanning as part of their presurgical evaluation. Normalized glucose metabolism was measured in the thalamus and caudate and lentiform nuclei, as well as in hippocampus, both ipsi- and contralateral to the epileptic focus, and correlated with duration and age at onset of epilepsy, presence or absence of secondary generalization, location of the epileptic focus, and extent of cortical glucose hypometabolism. RESULTS: Long duration of epilepsy was associated with lower glucose metabolism in the ipsilateral thalamus and hippocampus. Duration of epilepsy was a significant predictor of ipsilateral thalamic glucose metabolism in both temporal and frontal lobe epilepsy. Presence of secondarily generalized seizures also was associated with lower normalized metabolism in the ipsilateral thalamus and hippocampus. Extent of cortical hypometabolism did not correlate with subcortical metabolism, and glucose metabolism in the caudate and lentiform nuclei did not show any correlation with the clinical variables. CONCLUSIONS: The findings suggest that metabolic dysfunction of the thalamus ipsilateral to the seizure focus may become more severe with long-standing temporal and frontal lobe epilepsy, and also with secondary generalization of seizures.

Adolescent↗

PubMed2006

The effect of abdominal obesity on insulin sensitivity and serum lipid and cytokine concentrations in African women.

OBJECTIVES: Studies have shown clear associations of abdominal obesity with lipid and glucose metabolism and cytokine levels in a number of different population groups. However, no such studies have been performed in an African population in which visceral adipose tissue levels have been shown to be lower than in European subjects. DESIGN AND PATIENTS: Cross-sectional analysis in 124 African women. MEASUREMENTS: Fasting serum samples were taken from all subjects and anthropometric measurements obtained. Blood levels of glucose, insulin, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglyceride, interleukin (IL)-6, IL-8 and IL-18 were measured. Subjects were separated into normal and abnormal glucose tolerant groups and into tertiles according to waist circumference (WC). Insulin resistance was assessed using the homeostasis model assessment (HOMA). RESULTS: Abnormal glucose-tolerant subjects had higher WC, glucose and HOMA levels than the normal glucose-tolerant group. Increased WC was associated with higher triglyceride, insulin and HOMA levels and lower HDL levels. Multiple regression analyses showed that WC associated positively with HOMA and serum triglyceride levels and negatively with HDL levels. IL18 was a positive but weak determinant of the HOMA level and BMI correlated positively with serum IL-6 concentrations. CONCLUSIONS: Although previous studies have shown that African subjects have a lower visceral adipose depot size than European subjects, abdominal obesity is still associated with insulin resistance and dyslipidaemia. The association between abdominal obesity and metabolic dysfunction within this population is not dependent upon IL-6, IL-8 or IL-18.

Abdominal Fat↗

PubMed1995

Gastrointestinal motility in obesity.

Gastrointestinal motility is closely linked to the rate at which nutrients become systemically available. Regulation of gastric emptying represents the most important brake against delivery of nutrients to the intestine in excess of digestive and absorptive capacity. In man, gastric emptying is slowed in proportion to the energy density of the meal, which will level out the rate of energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in obesity, although the opposite has been reported in some experimental settings. Moreover, gastric volume is larger in obese individuals and appropriate satiety signals are not triggered in response to gastric distension. Postprandial intestinal transit time in obesity is similar to that in normal-weight subjects, however, despite this fact, intestinal absorption of nutrients is more efficient in obesity. Several regulatory mechanisms for gastrointestinal motility, such as the autonomous and enteric nervous systems and gastrointestinal regulatory peptides, are also of importance for feeding behaviour and metabolism. Dysfunction of the autonomous nervous system has been observed, the sensitivity to cholecystokinin is decreased in obesity, and plasma concentrations of somatostatin and neurotensin are lower than in normal-weight subjects. These changes in regulatory mechanisms favour rapid gastrointestinal transit of ingested nutrients and promote rapid intestinal absorption in obesity and decreased satiety in response to ingested food. It is presently not known whether the observed changes in gastrointestinal motility in obesity represent a primary feature linked to the pathogenesis of such disease.

Autonomic Nervous System↗

PubMed1991

Hypochlorous acid and myeloperoxidase-catalyzed oxidation of iron-sulfur clusters in bacterial respiratory dehydrogenases.

Hypochlorous acid and related oxidants derived from myeloperoxidase-catalyzed reactions contribute to the microbicidal activities of phagocytosing neutrophils and monocytes. Microbial iron-sulfur (Fe/S) clusters have been suggested as general targets of myeloperoxidase-derived oxidations, but no susceptible Fe/S site has yet been identified. In this study, the effects of HOCl and myeloperoxidase-catalyzed peroxidation of chloride ion upon EPR-detectable Fe/S clusters in Escherichia coli and Pseudomonas aeruginosa were examined. Increasing amounts of oxidant produced progressive loss of signal amplitudes from the S-1 and S-3 Fe/S clusters of succinate:ubiquinone oxidoreductase in respiring membrane fragments. These changes were compared to loss of microbial viability, succinate uptake rates, succinate dehydrogenase activity and succinate-dependent respiration. The amounts of oxidant required to destroy Fe/S clusters exceeded the amounts required to kill organisms or inhibit respiratory function by factors of four or five. Power saturation characteristics of the S-1 signal indicated that the S-2 signal was also resistant to modification, even in highly oxidized membranes. Loss of succinate-dependent respiration was closely associated with HOCl and myeloperoxidase-mediated microbicidal activity against P. aeruginosa and was also an early event in the oxidant-mediated metabolic dysfunctions of E. coli. However, these effects were not caused by the destruction of the Fe/S clusters within the succinate:ubiquinone oxidoreductase. Rather, the major respiration-inhibiting lesion(s) appeared to reside at points in the respiratory chain between the Fe/S clusters and the ubiquinone reductase site.

Electron Spin Resonance Spectroscopy↗

PubMedDate not supplied

Dose-dependent effect of alcohol on insulin-like growth factor systems in male rats.

1. Chronic alcohol treatment has been reported to be associated with liver and kidney damage. The insulin-like growth factor (IGF) is the major growth factor related to alcohol consumption. However, the effect of alcohol on the IGF system in the liver and kidney has not been fully elucidated. Thus, the present study was conducted to investigate this issue. 2. Alcohol reduced the level of IGF-I in a dose-dependent manner in the serum, liver and kidney. Alcohol also decreased the level of IGF-II in the liver. In contrast, alcohol increased the level of IGF-II in the serum and kidney. These observations were correlated with IGF-I and IGF-II mRNA expression in the liver and kidney. 3. To examine the effect of alcohol on IGF receptors in the liver and kidney, IGF-I receptor mRNA was measured. Alcohol decreased IGF-I receptor mRNA in the liver and kidney. 4. In experiments performed to examine the regulation of IGF-binding proteins (IGFBP), alcohol increased serum levels of IGFBP-1. However, alcohol had no effect on serum levels of IGFBP-2, -3 and -4. These effects were also observed in the liver and kidney. 5. In conclusion, alcohol alters the IGF system in rat liver and kidney in a tissue-specific manner, which may contribute to the metabolic dysfunction following chronic alcohol consumption.

Animals↗

PubMed1996

Serum carnitine and disabling fatigue in multiple sclerosis.

The serum concentrations of total, free and acylcarnitine were compared in 25 patients with multiple sclerosis (MS) and among age- and sex-matched normal controls by the new enzymatic cycling method in order to clarify whether the fatigue in MS might be due to possible carnitine-related fatty acid metabolic abnormalities in the mitochondria of skeletal muscles. Patients with MS were divided into those with and those without excessive fatigue. Levels of total and free carnitine were not significantly different between MS patients and normal controls. Levels of acylcarnitine, whose decrease in chronic fatigue syndrome has been reported, were also similar between MS patients and normal controls. There was no difference in these carnitine levels between MS patients with and without excessive fatigue. We argue that acylcarnitine deficiency and fatty acid metabolic dysfunction in mitochondria are not relevant to the excessive fatigue in patients with MS, and further explanatory investigations are to be sought.

Adult↗

PubMed2004

Ileal orthotopic neobladder (modified Hautmann) via a shorter detubularized ileal segment: experience and results.

OBJECTIVE: To evaluate the clinical, urodynamic, functional, radiological and metabolic results of the ileal (modified Hautmann) orthotopic neobladder over 10 years of experience. PATIENTS AND METHODS: Between January 1992 and March 2002, 124 men (mean age 62.4 years, range 44-76) with advanced bladder cancer had a radical cystoprostatectomy and urinary diversion via an ileal orthotopic neobladder (modified Hautmann). Only 40 cm of small bowel (detubularized ileum) was used to construct the reservoir, as a modification of the method described by Hautmann. All patients were followed periodically and their data recorded. RESULTS: While no patients died during surgery six died (mortality rate was 5%) in the first 30 days afterward (two of them from causes unrelated to the urinary diversion surgery). The early reoperation rate was 14%; there were early complications not requiring surgery in 40 (34%) and later reoperation rate was required in 20.6%. The mean (range) maximum neobladder capacity was 550 (310-720) mL, the maximum intravesical pressure at maximum capacity 26.4 (11-48) cmH(2)O, and the minimum and maximum flow rates 25.2 (16-64) and 17.5 (11-30) mL/s, respectively. Day- and night-time continence rates were 92% and 90% after 4 years. While there was no electrolyte imbalance, there was mild to moderate metabolic acidosis in 58% of patients. There was no urethral tumour recurrence in any patient. CONCLUSION: Detubularization of ileum to form a neobladder gives a more favourable low-pressure and high-capacity reservoir. Therefore, a shorter ileal segment can be used for orthotopic urinary diversion, to avoid various metabolic dysfunctions when using detubularized bowel, but the surgery is not as free of complications as the original technique.

Adult↗