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Biomedical subjects

J Borg

Publications and source records attributed to J Borg.

At least 37 records · Page 2Linked to original sources
PubMed1998

The effect of the nonpeptide neurotrophic compound SR 57746A on the progression of the disease state of the pmn mouse.

1. The progressive motor neuronopathy (pmn) mouse is an autosomal recessive mutant, in which the homozygotes suffer caudio-cranial degeneration of motor axons and die several weeks after birth. This strain provides the opportunity of testing potential therapeutic strategies for the treatment of motor neurone diseases such as amyotrophic lateral sclerosis. We have performed a study of the effects on the pmn mouse of SR 57746A, an orally-active, non-peptide compound which has been found to exhibit neurotrophic effects in vitro and in vivo. In order to treat the affected mice from birth, the mothers were administered 2.5 mg kg(-1). p.o., SR 57746A every two days until the weaning of the offspring (at day 20); then the offspring were given every two days a dose of 30 microg kg(-1), p.o., until their death. 2. Affected mice treated with SR 57746A had a lifespan 50% longer than that of the vehicle-treated mice (P=0.01). Compared to vehicle-treated pmn mice, SR 57746A improved the performance of the pmn mice in three different behavioural tasks. SR 57746A also maintained the amplitude of the motor evoked response of the gastrocnemius muscle, reduced the distal motor latency, and delayed the occurrence of the spontaneous denervation activity in this muscle. Histological studies indicated that at 20 days of age the mean surface areas of the fibres of the sciatic nerve were higher in SR 57746A-treated than in vehicle-treated mice. 3. At present, SR 57746A is the only orally active, nonpeptide compound known to be capable of delaying the progression of the motor neurone degeneration in pmn mice.

Animals↗
PubMed1998

Obstructive sleep apneas in relation to severity of cervical spinal cord injury.

Thirty-three subjects (28 men, five women) with complete or incomplete cervical cord injury representing a wide range of neurological impairment were investigated with regard to the prevalence of Obstructive Sleep Apnea (OSA). The relation between OSA and neurological function, respiratory capacity, body mass index and symptoms associated with OSA were studied. Overnight sleep recordings employed combined oximetry and respiratory movement monitoring. Pulmonary function tests included static and dynamic spirometry, maximal static inspiratory and expiratory pressures at the mouth. The subjects answered a questionnaire concerning sleep quality and tiredness. The prevalence of OSA was 15% (5/33) in this nonobese cervical cord injury study population. Nine percent of the subjects (3/33) fulfilled the criteria for obstructive sleep apnea syndrome, but daytime sleepiness or fatigue were also common in subjects without OSA. There was an inverse correlation between oxygen desaturation index and American Spinal Injury Association (ASIA) motor score in the subjects with complete injury, while there was no such correlation in the whole study group. There were significant correlations between maximal inspiratory and expiratory pressures and vital capacity and between ASIA motor score and vital capacity.

Adult↗
PubMed1997

MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure.

MLP is a LIM-only protein of terminally differentiated striated muscle cells, where it accumulates at actin-based structures involved in cytoarchitecture organization. To assess its role in muscle differentiation, we disrupted the MLP gene in mice. MLP (-/-) mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts were not hypertrophic, but already abnormally soft, with cell-autonomous and MLP-sensitive alterations in cytoarchitecture. Thus, MLP promotes proper cardiomyocyte cytoarchitecture, whose perturbation can lead to dilated cardiomyopathy. In vivo analysis revealed that MLP-deficient mice reproduce the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans, providing the first model for this condition in a genetically manipulatable organism.

Animals↗
PubMed1997

Progressive motor neuron impairment in an animal model of familial amyotrophic lateral sclerosis.

Mutations of Cu,Zn superoxide dismutase cause an autosomal dominant form of familial amyotrophic lateral sclerosis. An animal model of the disease has been produced by expressing mutant human SOD1 in transgenic mice (G93A). In order to quantify the dysfunction of the motor unit in transgenic mice, electromyographic recordings were performed during the course of the disease. The first alterations in neuromuscular function appeared between P63 and P90. The deficits became even more striking after P100; compound muscle action potentials in the hindlimb decreased by 80% of initial value. Spontaneous fibrillation potentials were measured in more than 50% of transgenic mice. The number of motor units in the gastrocnemius muscle was progressively reduced over time, down to 18% of the control value at P130. Moreover, distal motor latencies increased after P120. These data suggest that the initial dysfunctions of motor unit are related to a severe motor axonal degeneration, which is followed at later periods by myelin alteration.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Sternocleidomastoid muscle responses to transcranial magnetic stimulation in patients with cervical dystonia.

Ten cervical dystonia (CD) patients, with involuntary head rotation to one side and contralateral sternocleidomastoid muscle (SCM) hypertrophy, were investigated with transcranial magnetic stimulation, and the results were compared to those of 10 healthy subjects. Monopolar needle electrodes with isolated shafts were used for bilateral electromyographic recordings in the SCMs of the motor evoked potentials (MEPs) elicited by the magnetic stimulator. The latencies of ipsilateral SCM MEPs were shorter in the CD patients than in the control subjects (P < 0.001). The latencies of SCM activity suppression by TMS were longer in the CD patients than in the control group when stimuli were given on the contralateral side (P < 0.05). Both the clinically dystonic and the contralateral SCM of the CD patients exhibited significantly abnormal latencies of the ipsilateral SCM MEPs (P < 0.01) and of the SCM suppression (P < 0.05). Three CD patients also had consistent activity in the SCM counteracting the direction of head rotation during the suppression experiments. The latencies of the suppression of this abnormal activation were shorter (P < 0.05), than the latencies of the suppression in the SCM during normal voluntary activation by these CD patients (i.e. rotation of the head in the contrary direction). The results suggest bilaterally enhanced motoneuronal excitability and disturbed inhibitory regulation in patients with CD.

Adult↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗