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C Toth

Publications and source records attributed to C Toth.

At least 19 recordsLinked to original sources
PubMed2006

Remote neurotrophic support of epidermal nerve fibres in experimental diabetes.

AIMS/HYPOTHESIS: The support of distal regenerating axons and epidermal nerve fibres through growth factor delivery may depend on the site of delivery. While low-dose systemic insulin provides trophic support for regenerating axons or axons from diabetic animals, its potential action upon the most distal neurites within the epidermis is unknown. In diabetic neuropathy, distal loss of axons is an important clinical and pathological feature. We hypothesised that insulin and IGF-1 delivered intrathecally could support the most distal epidermal nerve fibres. MATERIALS AND METHODS: As insulin and IGF-1 receptors are present upon sensory ganglion perikarya, we studied the impact of intrathecal delivery of low-dose insulin and equimolar IGF-1 on the density of epidermal axons expressing protein gene product 9.5 in experimental diabetic rats. After 2 months of diabetes induced by streptozotocin injection, intrathecal delivery of low-dose insulin or IGF-1 or saline was provided for 1 month, with comparison to compatible doses of subcutaneous insulin delivery. RESULTS: Diabetes, in itself, was associated with a decline in epidermal nerve fibre density. Delivery of both intrathecal IGF-1 and insulin was associated with significant improvement in epidermal fibre density (greatest with IGF-1) and length relative to placebo. CONCLUSIONS/INTERPRETATION: Central intrathecal delivery of IGF-1 and insulin offers remote support for epidermal nerve fibres, subjected to 'dying-back' in early diabetic polyneuropathy.

Animals↗
PubMed2006

Rescue and regeneration of injured peripheral nerve axons by intrathecal insulin.

Insulin peptide, acting through tyrosine kinase receptor pathways, contributes to nerve development or repair. In this work, we examined the direction, impact and repertoire of insulin signaling in vivo during peripheral nerve regeneration in rats. First, we demonstrated that insulin receptor is expressed on lumbar dorsal root ganglia neuronal perikarya using immunohistochemistry. Immunoblots and polymerase chain reactions confirmed the presence of both alpha and beta insulin receptor subunits in dorsal root ganglia. In vivo and in vitro assessment of dorsal root ganglion neurons showed preferential localization of insulin receptor to perikaryal sites. In vivo, intrathecal delivery of fluorescein isothiocyanate-labeled insulin identified localization around dorsal root ganglia neurons. The direction and impact of potential insulin signaling was evaluated by concurrently delivering insulin or carrier over a 2 week period using mini-osmotic pumps, either intrathecally, near nerve, or with both deliveries, following a selective sural nerve crush injury. Only intrathecal insulin increased the number and maturity of regenerating sensory sural nerve axons distal to the crush site. As well, only intrathecal insulin rescued retrograde loss of sural axons after crush. In a separate experiment, insulin also rescued retrograde loss and atrophy of deep peroneal, largely motor, axons post-injury. Intrathecal insulin increased the expression of calcitonin-gene-related peptide in regenerating sprouts, increased the number of visualized regenerating fiber clusters, and reduced downregulation of calcitonin-gene-related peptide in dorsal root ganglia neurons. Insulin delivered intrathecally does not appear to influence expression of insulin-like growth factor-1 at dorsal root ganglion neurons or near peripheral nerve injury, but was associated with upregulation of insulin receptor alpha subunit in dorsal root ganglia. Intrathecal insulin delivery was associated with greater recovery of thermal sensation and longer distances to stimulus response with the pinch test following sural nerve crush. Insulin signaling at neuron perikarya can drive distal sensory axon regrowth, rescue retrograde alterations of axons and alter axon peptide expression. Moreover, such actions are associated with upregulation of its own receptor.

Animals↗
PubMed2006

Acetylcholine receptor antibodies in myasthenia gravis are associated with greater risk of diabetes and thyroid disease.

OBJECTIVE: Myasthenia gravis (MG) may be associated with the presence of acetylcholine receptor antibodies (AChRAb) [seropositive MG (SPMG)] or their absence [seronegative MG (SNMG)]. Along with features of MG, the presence of the AChRAb may relate to the existence of other immune-mediated diseases. We sought to determine the association of SPMG with other potential autoimmune diseases. METHODS: A retrospective evaluation of prospectively identified MG patients at a tertiary care center was performed, with patients separated into SPMG and SNMG. Prevalence of other immune-mediated disorders, as well as the epidemiology, sensitivity of diagnostic testing, and thymic pathology, was contrasted between both patient groups. RESULTS: Of the 109 MG patients identified, 66% were SPMG. SPMG was associated with a greater likelihood of significant repetitive stimulation decrement, the presence of either thymoma or thymic hyperplasia, and the presence of thyroid disease. In addition, all patients with a diagnosis of diabetes, concurrent with MG, were found to be SPMG. CONCLUSIONS: AChRAb and SPMG impart not only a distinctive clinical and electrophysiological phenotype of MG, but are also associated with the heightened presence of endocrinological disease.

Adolescent↗
PubMed2004

Diabetes mellitus and the sensory neuron.

Sensory neurons in diabetes may be primarily targeted by diabetes and their involvement may account for prominent sensory loss and pain in diabetic patients. Previous studies demonstrating evidence of excessive polyol flux, microangiopathy, and oxidative stress involving sensory axons and ganglia have been joined by more recent work demonstrating altered neuron phenotype, mitochondrial dysfunction, ion channel alterations, and abnormal growth factor signaling. As such, an interesting and unique panoply of molecular changes in primary sensory neurons has been identified in diabetic models. Insulin deficiency and subsequent changes in second messenger signaling may also play an important role in how sensory neurons respond to diabetes. Applying approaches to support sensory neurons in diabetes may be an important therapeutic direction in diabetic patients.

Animals↗
PubMed2003

Hemisensory syndrome is associated with a low diagnostic yield and a nearly uniform benign prognosis.

OBJECTIVE: To describe the diagnostic yield and prognosis for patients with hemisensory syndrome. BACKGROUND: The aetiology, utility of diagnostic procedures, and outcome of hemisensory syndrome in patients with exclusive hemibody complaints having only subjective sensory abnormalities on examination is unknown. METHODS: Patients were prospectively identified with hemisensory syndrome in a tertiary care institution from 1998-2002. Diagnostic procedures were analysed for sensitivity and clinical follow up was performed. RESULTS: Thirty four patients, 25 (74%) women, of age 35 (SD 11) years were identified. The hemisensory syndrome occurred on the left side in 23 (68%) cases. Neuroimaging of the brain demonstrated diagnostic abnormalities representing ischaemic aetiology in one case. Other diagnostic testing including cerebrospinal fluid examination, electrophysiological testing, carotid ultrasonography, echocardiography, and blood testing revealed no diagnostic abnormalities. Sixteen patients (47%) continued to complain of hemisensory difficulties after all investigations were completed at 9.6 (5.8) days. One patient with a history of systemic lupus erythematosus and positive antiphospholipid antibodies had a second event diagnosed as stroke seven months after presentation. Clinical follow up at 16 (7) months revealed persisting symptoms in 6 (20%) of 30 patients. Six (50%) of 12 patients agreeing to psychiatric assessment received diagnoses of personality or mood disorders. CONCLUSIONS: Diagnostic yield in hemisensory syndrome is low, and prognosis is almost always uniformly benign. The author advocates careful assessment of medical history and consideration for neuroimaging in this group of patients.

Adult↗
PubMed2002

Electron-yield enhancement in a laser-wakefield accelerator driven by asymmetric laser pulses.

The effect of asymmetric laser pulses on electron yield from a laser wakefield accelerator has been experimentally studied using >10(19) cm(-3) plasmas and a 10 TW, >45 fs, Ti:Al2O3 laser. The laser pulse shape was controlled through nonlinear chirp with a grating pair compressor. Pulses (76 fs FWHM) with a steep rise and positive chirp were found to significantly enhance the electron yield compared to pulses with a gentle rise and negative chirp. Theory and simulation show that fast rising pulses can generate larger amplitude wakes that seed the growth of the self-modulation instability, and that frequency chirp is of minimal importance for the experimental parameters.

Journal Article↗
PubMed2002

Supportive and palliative care: experience at the Institut Jules Bordet.

The Supportive and Palliative Care Unit of the Institut Jules Bordet officially started its activities in February 1999. Our Unit comprises eight beds (four rooms with one bed each and two rooms with two beds each). We admit advanced cancer patients presenting with severe symptoms whose control is going to require all the expertise of a multidisciplinary team. Whilst these eight beds are identified geographically in the hospital, the team's mobility assures continuity of care for patients who wish to stay in another department. The infrastructure of the Unit and its rooms allow close family members who wish to sleep close to the patients to do so. Otherwise, visits are allowed round the clock, though always with due consideration for patients' comfort. Patients are referred either by a physician working in our Institution (medical oncologist, surgeon, or radiotherapist) or by their family physicians. Less frequently, patients themselves specifically ask to be admitted to our Unit. The activity of the Unit itself during its first year of functioning can be summarized as follows. We admitted 155 advanced cancer patients, for a total number of 210 hospitalizations. Patients were admitted a median of 35 months after their diagnosis and a median of 20 days before death. Stays were generally short (median 11 days). We systematically used quantitative assessment tools (MMSQ, MDAS,EFAT and various VAS) to detect and monitor their symptoms and any complications. The main symptoms on admission were pain, anorexia, asthenia, dyspnea and anxiety/depression. Pain, nausea/vomiting, constipation and cough were controlled in almost all patients, whereas control of asthenia and anorexia was most often insufficient. In 51% of our cases the patients could be discharged home; 40% died in the unit; 4% were transferred to long-term palliative care units and 1% to other units within our Institution (4% were still hospitalized at the time of this analysis).

Adult↗
PubMed2001

Wernicke's encephalopathy following gastroplasty for morbid obesity.

BACKGROUND: The syndrome of Wernicke's encephalopathy consists of two of four features of (1) dietary deficiency; (2) oculomotor abnormality; (3) cerebellar dysfunction; and (4) confusion or mild memory impairment. Predisposing risk factors include alcoholism, hyperemesis gravidarum and prolonged intravenous feeding. METHODS: A 35-year-old female developed refractory emesis, severe weight loss, and hypokalemia following banded gastroplasty for morbid obesity. Reversal of gastroplasty was performed four months following initial surgery. Following reversal, the patient developed confusion, ataxia, leg weakness and nystagmus. RESULTS: Examination of the patient demonstrated disorientation with confusion, vertical nystagmus worse on downgaze, diffuse weakness of the lower extremities, and bilateral dysmetria. Magnetic resonance imaging of the brain demonstrated symmetrical areas of increased T2 signal present bilaterally in the medial thalamic nuclei. The patient did not demonstrate any initial improvement with intravenous thiamine but improved over two months of follow-up. CONCLUSION: Wernicke's encephalopathy has been reported in the European literature as a complication of gastroplasty, with rare recognition of this clinical entity in the North American literature. This potential complication of gastroplasty may be preventable by nutritional intervention in subjects experiencing severe weight loss and emesis following surgery.

Adult↗
PubMed2001

Mandibular reconstruction with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: an experimental study in miniature pigs. Part II: transplantation.

Osteogenic Protein-1 (rhOP-1), also called bone morphogenetic protein-7 (BMP-7), is osteoinductive. The aim of this study was to present a new surgical technique: the prefabrication of a vascularized bone graft using rhOP-1 and its microsurgical transplantation. During 6 weeks, osteomuscular grafts were prefabricated in the latissimus dorsi muscle of five adult minipigs. Six hundred micrograms rhOP-1 on a carrier of xenogenic bone mineral in block form were used. The grafts were transplanted into defects of the mandibular angles performing a microsurgical anastomosis and using miniplates for fixation. Identical defects of the contralateral side were treated by direct application of 600 microg rhOP-1 and xenogenic bone mineral. A polychrome sequential labelling was applied. After transplantation the bone stayed viable, demonstrated by continuous apposition of fluorochromes (non-decalcified histologic sections) and bone scintigraphy. The reconstructive result was significantly superior in the prefabrication technique, assessed by histology and computerized tomography (CT). In conclusion, the method has a potential to become a clinical alternative for conventional vascularized bone grafts.

Anastomosis, Surgical↗
PubMed1999

Regulated degradation of yeast ornithine decarboxylase.

Ornithine decarboxylase (ODC) declines in cells that accumulate an excess of polyamines, the downstream products of the enzyme. Superfluous production of polyamines is thus prevented. In animal cells, polyamines reduce ODC activity by accelerating its degradation. Similar down-regulation of ODC activity has been observed in the budding yeast Saccharomyces cerevisiae, but induced degradation has not been documented. Here we show using pulse-chase analysis that the loss of enzyme activity is the result of increased degradation of ODC. Polyamines reduce the half-life of the newly synthesized protein from 3 h to approximately 10 min. Degradation of bulk ODC pools is also accelerated by polyamines, but the absolute rate of turnover is slower, with a half-life of 5 h in untreated and 1 h in treated cells. Newly synthesized ODC polypeptide thus undergoes a process of maturation that renders it relatively resistant to both basal and polyamine-induced degradation. Proteasome mutants have a blunted or absent regulatory response, implicating both the core protease and the regulatory cap of the proteasome in induced degradation of yeast ODC.

Down-Regulation↗
PubMed1999

Deep brain stimulation of the ventral intermediate nucleus of the thalamus for control of tremors in Parkinson's disease and essential tremor.

The beneficial effects of ventral intermediate nucleus (VIM) stimulation were evaluated in 20 patients with tremor refractory to medical therapy. Thalamic stimulation is a non-ablative procedure which has the advantage of a reversible, non-destructive lesion. Eleven patients [7 with Parkinson's disease (PD) and 4 with essential tremor (ET)] received unilateral VIM implantation, while 9 patients had staged bilateral VIM implantation (4 with PD, 5 with ET). PD patients showed a significant improvement in contralateral arm and leg rest tremor and ipsilateral leg rest tremor (p < 0.02) at a mean follow-up period of 16.2 +/- 7.0 months. Patients with PD did not demonstrate any significant decrease in medication use at follow-up. ET patients demonstrated significant improvement in postural and action tremor in the contralateral arm (p < 0.001), but no significant improvement in the contralateral leg tremor at follow-up. Significant improvements were also seen in ET patients in the Clinical Rating Scale for Tremor (p < 0.001) with respect to several activities of daily living at a mean follow-up of 14.9 +/- 8. 1 months. Deep brain stimulation is a safe and effective treatment for severe tremor refractory to medications. It is a highly effective, reversible, adaptable, and predictable procedure which avoids the complication of cognitive deficit seen in patients with bilateral thalamotomies.

Aged↗
PubMed1999

Indoor, outdoor, and regional summer and winter concentrations of PM10, PM2.5, SO4(2)-, H+, NH4+, NO3-, NH3, and nitrous acid in homes with and without kerosene space heaters.

Twenty-four-hour samples of PM10 (mass of particles with aerodynamic diameter < or = 10 microm), PM2.5, (mass of particles with aerodynamic diameter < or = 2.5 microm), particle strong acidity (H+), sulfate (SO42-), nitrate (NO3-), ammonia (NH3), nitrous acid (HONO), and sulfur dioxide were collected inside and outside of 281 homes during winter and summer periods. Measurements were also conducted during summer periods at a regional site. A total of 58 homes of nonsmokers were sampled during the summer periods and 223 homes were sampled during the winter periods. Seventy-four of the homes sampled during the winter reported the use of a kerosene heater. All homes sampled in the summer were located in southwest Virginia. All but 20 homes sampled in the winter were also located in southwest Virginia; the remainder of the homes were located in Connecticut. For homes without tobacco combustion, the regional air monitoring site (Vinton, VA) appeared to provide a reasonable estimate of concentrations of PM2.5 and SO42- during summer months outside and inside homes within the region, even when a substantial number of the homes used air conditioning. Average indoor/outdoor ratios for PM2.5 and SO42- during the summer period were 1.03 +/- 0.71 and 0.74 +/- 0.53, respectively. The indoor/outdoor mean ratio for sulfate suggests that on average approximately 75% of the fine aerosol indoors during the summer is associated with outdoor sources. Kerosene heater use during the winter months, in the absence of tobacco combustion, results in substantial increases in indoor concentrations of PM2.5, SO42-, and possibly H+, as compared to homes without kerosene heaters. During their use, we estimated that kerosene heaters added, on average, approximately 40 microg/m3 of PM2.5 and 15 microg/m3 of SO42- to background residential levels of 18 and 2 microg/m3, respectively. Results from using sulfuric acid-doped Teflon (E.I. Du Pont de Nemours & Co., Wilmington, DE) filters in homes with kerosene heaters suggest that acid particle concentrations may be substantially higher than those measured because of acid neutralization by ammonia. During the summer and winter periods indoor concentrations of ammonia are an order of magnitude higher indoors than outdoors and appear to result in lower indoor acid particle concentrations. Nitrous acid levels are higher indoors than outdoors during both winter and summer and are substantially higher in homes with unvented combustion sources.

Air Pollutants↗
PubMed1998

Epidural spinal cord stimulation for treatment of chronic pain--some predictors of success. A 15-year experience.

BACKGROUND: We have used epidural spinal cord stimulation (SCS) for pain control for the past 15 years. An analysis of our series of 235 patients has clarified the value of specific prognostic parameters in the prediction of successful SCS. METHODS: Patients were followed up for periods ranging from 6 months to 15 years with a mean follow-up of 66 months. The mean age of the 150 men and 85 women in the study was 51.4 years. Indications for SCS included failed back syndrome (114 patients), peripheral vascular disease (39 patients), peripheral neuropathy (30 patients), multiple sclerosis (13 patients), reflex sympathetic dystrophy (13 patients), and other etiologies of chronic intractable pain (26 patients). RESULTS: One hundred and eighty-nine patients received permanent devices; 111 (59%) of these patients continue to receive satisfactory pain relief. Pain attributable to failed back syndrome, reflex sympathetic dystrophy, peripheral vascular disease of lower limbs, multiple sclerosis, and peripheral neuropathy responded favorably to spinal cord stimulation. In contrast, paraplegic pain, cauda equina syndrome, stump pain, phantom limb pain, and primary bone and joint disease pain did not respond as well. Cases of cauda equina injury had promising initial pain relief, but gradually declined after a few years. After long-term follow-up, 47 of the 111 successfully implanted patients were gainfully employed, compared with 22 patients before implantation. The successful patients reported improvements in daily living as well as a decrease in analgesic usage. Multipolar stimulation systems were significantly more reliable (p < 0.001) than unipolar systems. Complications included hardware malfunction, electrode displacement, infection, and tolerance. CONCLUSION: Aside from etiologies of pain syndromes as a prognostic factor, we have identified other parameters of success. In patients who have undergone previous surgical procedures, the shorter the duration of time to implantation, the greater the rate of success (p < 0.001). The diagnosis of failed back syndrome must be considered a confounding factor in our analysis. Those patients whose pain did not follow a surgical procedure had better responses to SCS than patients who had multiple surgical procedures prior to their first implant. The advent of multipolar systems has significantly improved clinical reliability over unipolar systems. Age, sex, and laterality of pain did not prove to be of significance.

Adult↗
PubMed1998

Focal plaque of demyelination mimicking cerebral tumor in a pediatric patient.

Focal, demyelinating lesions of the cerebrum mimicking brain tumors are a rare phenomenon, and even rarer in a pediatric population. We document the case of a 14-year-old female whose clinical, radiological and operative findings were strongly suggestive of glioma. However, histopathology revealed a demyelinating process. This case is significant as the lesion could not be distinguished from a glioma at any time in the presentation. At 41 months follow-up, the patient remains stable without further evidence of demyelination in other areas of the brain. Such a case suggests a cautious note for the pediatrician when presented with a similar patient and illustrates the importance of consideration of a demyelinating lesion in the differential diagnosis of a mass lesion in a pediatric population.

Adolescent↗