[Botulinum toxin--from threat to cure].
Explore the source record for details and available documents.
Anti-Dyskinesia Agents↗
Biomedical subjects
J Borg
Publications and source records attributed to J Borg.
Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol.
The purpose of the present study was to determine the effects of n-hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 +/- 0.15 mm/day and 1.09 +/- 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and and sensorimotor tests. Clinical signs of recovery evaluation with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 +/- 0.15 mV/day; control: 2.00 +/- 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.
Animals↗
Electromyographical and motor performance studies in the pmn mouse model of neurodegenerative disease.
The mouse autosomal recessive mutation progressive motor neuronopathy (pmn) results in early onset motor neuron disease with rapidly progressive hindlimb paralysis, severe muscular wasting, and death at around 6 weeks of age. This mutant provides opportunities for testing novel therapeutic strategies, including the administration of trophic factors, to prevent the degeneration of diseased neurons. The construction of a strain expressing the pmn and the Extra-toe (Xt) phenotypes allows the detection, and therefore the treatment, of affected progeny before the onset of the clinical weakness. Electromyography is the most appropriate technique for a longitudinal study in which a given individual is examined repeatedly. We present the results of an electrophysiological and behavioral exploration of the pmn disease and show that electromyography is a powerful tool for following the course of the disease and evaluating potential therapies relevant to motor neuron diseases.
Action Potentials↗
Intractable constipation with a decrease in substance P-immunoreactive fibres: is it a variant of intestinal neuronal dysplasia?
After Hirschsprung's disease was ruled out for 25 children who had severe chronic constipation, the authors studied the distribution of immunoreactivity for substance P (SP) and vasoactive intestinal peptide (VIP) in the intestinal wall, using immunofluorescence. SP and VIP immunoreactivity identify excitatory and inhibitory nerve fibres, respectively. Full-thickness rectal biopsy specimens were unsatisfactory, so seromuscular biopsies of the caecum, transverse colon, and sigmoid colon were obtained (by laparoscopy and laparotomy; n = 10 patients). SP-immunoreactive fibres were markedly reduced in seven, with concomitant reduction of VIP-immunoreactive fibres in four. In two other patients, there was no obvious reduction in SP- or VIP-immunoreactive fibres. In a patient who subsequently was found to have multiple endocrine neoplasia type 2b, the myenteric plexus was markedly hyperplastic, with an increase in nerve cells and nerve fibres. VIP-immunoreactive fibres were increased, but SP-immunoreactive fibres were markedly decreased. Surgical options included proximal stoma, Malone operation, and subtotal colectomy with preservation of the rectum. Three children with subtotal colectomy have had improvement over short-term follow-up. The combination of seromuscular laparoscopic biopsies and immunofluorescence demonstration of neuropeptides may identify new variants of intestinal neuronal dysplasia than can be treated successfully with surgery.
Adenomatous Polyposis Coli↗
Annulate lamellae and lytic HAV infection in vitro.
The aim of this study was to examine the relationship between viral infection and annulate lamellae (AL) production by using quantitative and qualitative electron microscopy to document the size and numbers of AL in BS-C-1 cells infected with a lytic strain of hepatitis A virus (HAV). The progress of the HAV infection was found to occur in two phases. In phase 1, cell proliferation and cell death were roughly the same as that of the mock infected control, but there was an increase with time in the amount of hepatitis A antigen in the infected cells. In phase 2 cell division was minimal and cell death became manifest. AL were detected in both infected and control cells. Quantitative analysis indicated that the average number of AL was greater in infected cells compared to that in control cells in phase 1; in infected cells there were greater numbers of AL in phase 1 than in phase 2; the average number of membraneous leaves/AL was greater in infected cells than in control cells. Quantitative analysis also indicated that AL were very rare, with only about three AL per entire control cell and eight AL per entire infected cell. The study clearly establishes that viral infection can stimulate AL production. The data suggest stimulation of AL production in the virus infected cells was linked to the synthesis of viral antigen. Ultrastructural observations indicated that AL could be derived from either the rough endoplasmic reticulum or the nuclear membrane.
Animals↗
Diaphragm function in patients with cervical cord injury or prior poliomyelitis infection.
Diaphragm function was evaluated in cervical cord injury patients (CCI), 1-3 years after injury (CCI(1-3)) and 10 years or more after injury (CCI(> or = 10)), as well as in a group of prior poliomyelitis infection patients (PPI), requiring intermittent positive pressure ventilation (IPPV) for about 6 h per night. Measurements included transdiaphragmatic pressure swings (delta Pdi) at rest, during maximal inspiratory efforts against closed airways (delta Pdi(max)) and during sniff manoeuvres (ie maximal inhalation through the nose, delta Pdi(sniff)), vital capacity normalized to age and height (VC(%pred)), tidal volume (Vt), relative inspiratory time (Ti/Ttot), breathing frequency (f(b)), and the tension-time index of the diaphragm (TTdi = delta Pdi/delta Pdi(max) x Ti/Ttot). The median VC(%pred) was 50% in the CCI(1-3) group and 57% in the CCI (> or = 10) group, but only 28% in the PPI group. Delta Pdi(max) values were similar for the CCI(1-3) (11.8 kPa) and CCI(> or = 10) (11.9 kPa) groups but were lower (71. kPa) in the PPI group. Due to the reduction in delta Pdi(max), the PPI group had higher delta Pdi/delta Pdi(max) values than the CCI groups, however, the TTdi was similar amongst the different groups studied. A submaximal exercise test in five cervical cord injury patients and in five polio patients with similar delta Pdi(max), delta Pdi(sniff) and TTdi values at rest revealed clear group differences with respect to force development, in that CCI patients showed significant increases in TTdi, while PPI demonstrated only minor changes. In CCI patients, an increase in ventilation was accompanied by an increase in delta Pdi/delta Pdi(max) while in contrast, the PPI patients showed no increase in delta Pdi/delta Pdi(max). We conclude that CCI patients, both recently and previously injured, have a similar maximal inspiratory force and are less impaired than the PPI patients. The TTdi at rest is similar in all groups, but the PPI patients react to inspiratory loads with little increases in TTdi, while the CCI patients increase their TTdi above fatiguing (0.15) levels. The different behaviours may be linked to loss of sensory pathways in the CCI patients.
Adult↗
Impaired sensory-motor integration during grasping in writer's cramp.
Six subjects with writer's cramp and six healthy control subjects were examined while lifting a small instrumented object with variable weight and friction using the precision grip. The isometric grip and load forces were sampled at 400 Hz and stored in a flexible laboratory computer system for later analysis. Quantitative measurement of vibration and temperature sensibility showed normal sensory perception in the writer's cramp subjects. They exhibited an impaired programming of the grip-lift force co-ordination, while the ability to generate unimodal force-rate trajectories and to characterize the pattern of the force output according to memory representations of weight and friction of the object were intact. The capacity to terminate quickly the programmed grip force in lifts erroneously programmed too high was impaired. Writer's cramp subjects also employed excessive grip force during the static phase of the lift, and some patients had a short grip force latency after sudden unpredicted load increases, indicating a disinhibited spinal reflex response. The results indicate an impaired capacity in writer's cramp subjects to integrate sensory information in the motor programming and force regulation during precision grip tasks, despite a normal sensibility.
Adult↗
Magnetic resonance imaging of lower extremity muscles and isokinetic strength in foot dorsiflexors in patients with prior polio.
The thigh and lower leg of six patients with prior polio were examined using magnetic resonance imaging (MRI), and the strength of their weak foot dorsiflexors was measured isokinetically. Spinecho images of the lower extremities were visually evaluated on a semi-quantitative four-point scale, and T1 and T2 relaxation times of the lower leg anterior compartment were analysed. There were prominent MRI signs of randomly distributed muscle degeneration. The high signal intensity changes in the affected muscles on T1-weighted images and T1 and T2 values indicated replacement of muscle fibres with fat and the accumulation of tissue water, respectively. MRI findings were compared with isokinetic strength in foot dorsiflexor muscles. Foot dorsiflexor peak torque values at 30 deg/s ranged from 6 to 29 Nm. There was no significant correlation between MRI visual scoring, T1 and T2 relaxation times and peak torque values at 30 deg/s. However, the most severe MRI changes with visual scoring and T2 relaxation times were observed in the patients with the most pronounced muscle weakness.
Aged↗
Motoneuron and muscle fiber properties of remaining motor units in weak tibialis anterior muscles in prior polio.
Explore the source record for details and available documents.
Adaptation, Physiological↗
Effect of n-hexacosanol on insulin secretion in the rat.
n-Hexacosanol, a long-chain saturated fatty alcohol extracted from Hygrophyla erecta Hochr., has been recently shown to exert neurotrophic properties on central neurons and to stimulate phagocytosis in macrophages. The present work was designed to investigate the effects of hexacosanol on stimulated insulin secretion in vivo and in vitro. In anaesthetized rats, hexacosanol (2 mg/kg i.p.) induced a reduction of the insulin response to an intravenous glucose tolerance test (0.3 g/kg) with a consequent increase in hyperglycaemia. In vitro, in the isolated perfused pancreas, hexacosanol at the concentration of 10(-7) M clearly reduced the two phases of glucose-induced insulin secretion. At the higher concentration (10(-5) M), hexacosanol was no longer able to exert an inhibition of glucose-induced insulin release; surprisingly a stimulating effect occurred which was of the same magnitude as in control experiments with Tween alone, at the concentration used to dissolve hexacosanol. In isolated perifused islets, 22 mM glucose-stimulated insulin release was also inhibited by hexacosanol at the concentrations of 10(-9) M and 10(-7) M, but not at 10(-5) M. In contrast, insulin secretion induced by arginine (20 mM) was not affected by the different concentrations of hexacosanol. It is concluded that n-hexacosanol at 10(-9) M and 10(-7) M exerts an inhibitory effect on insulin secretion stimulated by glucose in vivo and in vitro in the rat, suggesting a direct effect on islets of Langerhans.
Analysis of Variance↗
Single X-ray absorptiometry: performance characteristics and comparison with single photon absorptiometry.
The aim of the present study was to evaluate a new device for measurement of forearm bone mass using the technique of single X-ray absorptiometry (SXA, DTX-100; Osteometer A/S, Rødovre, Denmark), and to compare the performance with the more traditional single photon absorptiometry (SPA, DT 100; Osteometer A/S, Rødovre, Denmark). The SPA phantom measurements showed a coefficient of variation of 0.43% and 0.42% for bone mineral content (BMC) and bone mineral density (BMD), respectively (39 months including seven source changes). The SXA precision errors were slightly lower with values of 0.30% and 0.30%, respectively. The patient measurements showed SPA coefficients of variation of 0.85% and 0.99% (BMC and BMD) and SXA coefficients of variation of 0.56% and 0.83%, respectively. The correlation between SPA and SXA values performed in 377 individuals yielded r values of 0.99 and 0.98 for BMC and BMD, respectively. The correlations between SXA measurements of the dominant and non-dominant forearm yielded an r-value of 0.95, with a slope of 0.949 (p < 0.001) and an intercept of 0.204 (p < 0.05). The non-dominant forearm thus had approximately 3% lower BMC than the dominant (the same was true for BMD). Correlations to spine and femur ranged from r = 0.48 to r = 0.75. In conclusion, the new single X-ray absorptiometry forearm bone densitometer described in this paper has performance characteristics which allows it to be used both for diagnostic purposes and for the follow-up of treatment.
Absorptiometry, Photon↗
Human chorionic gonadotrophin self-administered by the subcutaneous route to induce oocyte maturation in an in-vitro fertilization and embryo transfer programme.
This study was initiated to evaluate oocyte maturation and the outcome of in-vitro fertilization (IVF) cycles following the s.c. administration of human chorionic gonadotrophin (HCG) by the patient herself or her partner. A group of 104 women who entered our IVF embryo transfer programme were prospectively randomized to have 5000 IU or 10,000 IU HCG s.c. or i.m. The HCG was administered for induction of the final oocyte maturation in cycles with pituitary down-regulation with a gonadotrophin-releasing hormone agonist according to a long protocol and where ovarian stimulation had been achieved with pure follicle stimulating hormone. The mean concentration of HCG in serum 12 and 36 h after the HCG injection was significantly higher in the women receiving 5000 IU i.m. compared to the s.c. route. However, in women receiving 10,000 IU HCG there were no significant differences in the mean concentrations 12 and 36 h after the injection, irrespective of the route of administration. Furthermore, there were no significant differences in the relative numbers of retrieved mature oocytes between the groups. When comparing the clinical outcome in the different groups, no significant differences were found between those receiving 5000 IU or 10,000 IU HCG, i.m. or s.c. Our data indicate that HCG can be given s.c. without reducing the chance of retrieving a mature oocyte and that the clinical outcome with regard to pregnancies is not negatively affected.
Adult↗
Electromyographic single motor unit potentials after repeated botulinum toxin treatments in cervical dystonia.
Electromyographic (EMG) single motor unit potentials (MUPs) of the sternomastoid muscles (STM) were made before and after repeated treatment with botulinum type A toxin (Bx) for cervical dystonia. Post-treatment examinations were 6-25 weeks after the latest injection, when symptoms and EMG interference pattern had recurred and signs of denervation were scarce. Concentric needle EMG records of 200 motor unit potentials in 10 patients showed reduced durations and areas after treatment (P < 0.05). Increased polyphasia or satellite potentials were not observed. Macro-EMG records of 110 MUPs in 6 patients showed reduced amplitudes and areas in the injected STM when compared to the untreated side (P < 0.05). Fibre density was within the same range (1.0-1.2). The results indicate that the pattern of the terminal innervation is mainly restored even after repeated Bx treatments, but the number or size of active muscle fibres within the motor unit is reduced. The clinical relapse could be due to recovery of the original nerve terminals, or to nerve sprouts closely imitating the blocked terminal nerve twigs or both.
Adult↗
Simplification of IVF: minimal monitoring and the use of subcutaneous highly purified FSH administration for ovulation induction.
During the past few years much effort has been put into simplifying the clinical management of in-vitro fertilization/embryo transfer cycles. One important step was the introduction of transvaginal ultrasound-guided oocyte collection, as previously described. This study describes further simplifications of the clinical management of ovarian stimulation. During the period 1st January 1991 to 31st August 1993, three major simplification steps were introduced. All cycles were down-regulated with a gonadotrophin-releasing hormone (GnRH) agonist according to a long protocol permitting fairly precise programming of the oocyte collection. During period I (n = 329 cycles), closer monitoring by several pelvic ultrasound scans and serum oestradiol was used for monitoring the ovarian stimulation. During period II (n = 230 cycles), only one ultrasound scan was used for monitoring the ovarian cycle; oocyte collections during weekends were avoided. During period III (n = 386 cycles), further simplification of the clinical management was introduced by using a highly purified follicle stimulating hormone (FSH) (Fertinorm/Metrodin HP), which was self-administered s.c. for ovarian stimulation. The take-home baby rates per started cycle for periods I, II and III were 16.4, 32.6 and 31.3% respectively. These figures indicate that when using long down-regulation with a GnRH agonist, simplification of the monitoring of the ovarian stimulation is possible without decreasing the pregnancy rate. Furthermore, the use of a highly purified FSH, self-administered s.c., greatly simplified treatment without compromising cycle outcome or increasing the risk of developing an ovarian hyperstimulation syndrome.
Adult↗
Efficacy of botulinum toxin for cervical dystonia. A comparison of methods for evaluation.
Twenty patients with cervical dystonia were treated during one year with repeated intramuscular injections of botulinum toxin. The outcome was evaluated comparing subjective global rating with relative changes in degree of pain on the Visual analogue scale (VAS), degree of dysfunction due to dystonia, and quality of life according to the Nottingham health profile (NHP). Objective measurement of dystonic position and movement ability was performed using a goniometer, semiquantitatively noted as scores according to Fahn and Tsui. Before treatment, the degree of impaired life quality on the NHP did not correlate with the Tsui score of dystonic posture, but significantly with the Fahn score (p < 0.01) which also includes data on pain. Significant improvement after treatment was seen for all parameters (p < 0.05). Global subjective rating correlated significantly with improved posture according to the Tsui score (p < 0.05), but not with reduced pain or degree of dysfunction. The results suggest that the efficacy of botulinum toxin in cervical dystonia is best evaluated using a combination of the VAS for pain and the Tsui score for dystonic posture and movement ability.
Activities of Daily Living↗
Fetal tissue involvement in the late infantile type of neuronal ceroid lipofuscinosis.
Prenatal diagnosis in a pregnancy at risk for late infantile neuronal ceroid lipofuscinosis (Batten's disease) was undertaken at 17 weeks' gestation by ultrastructural examination of amniotic fluid cells. The presence of curvilinear profiles indicated an affected fetus and the diagnosis was confirmed, after the pregnancy was terminated, by the finding of many typical curvilinear profiles in multiple tissues which included skin, amnion, umbilical vessels, blood, liver, and brain. Comparison between the involved cells in the amniotic fluid and fetal tissues suggests that these cells are probably derived from the periderm, and possibly also from the amnion. The prominent presence of cytosomes in the periderm and intermediate cells of the fetal epidermis and occasionally also in the endothelial cells of the dermis suggests that fetal skin may be a useful alternative site for assessing fetal involvement. Control specimens of the amniotic fluid, fetal skin, amnion, and liver showed no similar cytosomes. However, some control amniotic fluid samples did contain cells with large collections of irregular trilaminar membranes, and these could be open to misinterpretation. It is important that only typical curvilinear profiles are considered as an indication of an affected pregnancy.
Abortion, Therapeutic↗
Isokinetic strength, macro EMG and muscle biopsy of paretic foot dorsiflexors in chronic neurogenic paresis.
Ten ambulatory patients with chronic dorsiflexor paresis due to prior poliomyelitis or lumbar root (LV) lesion and without recent decline of the foot dorsiflexor strength were examined with isokinetic strength measurement, macro EMG and muscle biopsy. Isokinetic strength measurement showed peak torques at 30 degrees/s angular velocity ranging 6-44 Nm and at 240 degrees/s 1-10 Nm. Mean of individual median macro EMG motor unit potential amplitudes was 2020 microV (SD 1040) which was 5-10 times higher than expected values in healthy subjects. Muscle biopsies showed a mean type 1 fibre proportion of 91% (SD 14) and a mean type 1 fibre area of 8561 microns 2 (SD 2773) which was about 2 times larger than those observed in healthy subjects. Peak torque and both motor unit potential amplitude and area were inversely correlated at 30 (p < 0.01 and p < 0.025), 60 (p < 0.025 and p < 0.025) and 120 (p < 0.05 and p < 0.05) degrees/s angular velocity, as were peak torque and type 1 muscle fibre proportion at 30 (p < 0.05) and 60 (p < 0.05) degrees/s angular velocity. Peak torque or macro EMG parameters were not correlated to muscle fibre area. The data suggest that the remaining muscle strength was directly correlated to the degree of collateral sprouting and that about half of it could be attributed to compensatory muscle fibre hypertrophy.
Aged↗
A new nasal mask for nocturnal home ventilation in chronic neuromuscular disorders.
A new nasal mask for nocturnal, intermittent positive pressure ventilation was used by patients with symptomatic sleep hypoventilation due to chronic neuromuscular disorders. The custom-fabricated mask is cast in visible light curing acrylic from a plaster model. Air is delivered through plastic tubes cast in the mask. The treatment was introduced through close cooperation between a physiotherapist and a technician. Evaluation was performed after 4-34 months' regular use. The mask was well tolerated. All patients reported comfortable sleep and symptom relief. The effectiveness was confirmed by whole-night measurements of oxygen saturation and end-tidal carbon dioxide.
Adult↗