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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

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

Studies on the immunological effects of fatty alcohols--I. Effects of n-hexacosanol on murine macrophages in culture.

n-Hexacosanol (hexa), a long chain fatty alcohol extracted from Hygrophila erecta, has proved to possess neurotrophic activities on cultured neurons, and to attenuate the degeneration of cholinergic neurons after injury. In the present study, we show that hexa has also interesting properties on macrophages, a cell type largely represented in the brain: when added to mice resident peritoneal macrophages, it provokes significant morphological changes, and increases their phagocytosis capacity. These results may indicate that some membrane properties involved in these different effects and in macrophage functions are affected by n-hexacosanol, but other sites of action could also be considered.

Animals

Torque-velocity relation and muscle fibre characteristics of foot dorsiflexors after long-term overuse of residual muscle fibres due to prior polio or L5 root lesion.

Isokinetic foot dorsiflexion strength and muscle biopsy data from eight patients with overuse of tibialis anterior muscle (TA) fibres due to weakness after prior polio or L5 root lesion were compared to data from age and sex matched, healthy subjects. Concentric peak torque at an angular velocity of 30 degrees/s was 6-24 Nm in the patients and 15-34 Nm in the controls (p < 0.01). Muscle biopsies from TA showed a significantly higher proportion of type 1 fibres in the patients as compared to the controls (p < 0.005). The type 1 fibres in the patients had a significantly larger cross-sectional area than in the controls (p < 0.005). The type 1 fibre proportion and relative area were inversely correlated to the relative concentric torque produced at 180 degrees/s (p < 0.05) and 240 degrees/s (p < 0.05) compared to that produced at 30 degrees/s in the controls but not in the patients. However, the relative concentric torque produced at 180 degrees/s and 240 degrees/s compared to that produced at 30 degrees/s was not significantly different in the patients and the controls. This indicates that the contractile properties of the overused muscle fibres do not change in parallel with the histochemical fibre type.

Aged

The neurotrophic factor, n-hexacosanol, reduces the neuronal damage induced by the neurotoxin, kainic acid.

The long-chain fatty alcohol, n-hexacosanol, has been shown to possess neurotrophic properties in vitro on rat CNS cultures (Borg et al., 1987) and to promote the survival of septal cholinergic neurons after experimental axotomy (Borg et al., 1990). Long-chain alcohols have also been shown to be synthesized and metabolised by rat brain during development (Bishop and Hayra, 1981; Natarajan et al., 1984). The present study was undertaken in order to find out if a nonproteic neurotrophic factor like n-hexacosanol may be able to reduce the neuronal damages induced by the excitatory amino acid, kainic acid. When administered chronically by intraperitineal injection, hexacosanol (1 mg/kg) protected the pyramidal neurons of the hippocampus from the neurotoxic degeneration induced by an intracerebroventricular infusion of kainic acid in rats; the extent of the damage was limited to a small part of the CA3 region. Morphometric analysis showed that 72% of the neurons that would have died following kainic acid injection were spared by hexacosanol. Moreover the increased locomotor activity induced by the neurotoxin was also inhibited by hexacosanol and the behavioral effect was statistically correlated to the extent of neuronal loss. The present study suggests a possible role for nonproteic neurotrophic compounds against neurotoxic damages on central neurons. Moreover the peripheral administration of hexacosanol may lead to a significant breakthrough in the treatment of exicotoxin-related human diseases.

Animals

Welander's distal myopathy: clinical, neurophysiological and muscle biopsy observations in young and middle aged adults with early symptoms.

Nine young or middle aged patients with early symptoms of Welander's distal myopathy were subjected to a detailed neurological examination including quantitative sensory testing, determination of motor and sensory nerve conduction velocity (NCV), sensory nerve action potentials, electromyography (EMG) and muscle biopsy from the tibialis anterior muscle (TA). Slight weakness of the extensors of the fingers and hands was found in all nine patients, and of the dorsiflexors of the feet in seven. All patients had a distal sensory disturbance most prominent for temperature which agrees with earlier observations. EMG changes in TA and extensor digitorum communis (EDC) muscles were of myopathic type. Slight abnormalities compatible with either myopathy or early neuropathy were found in one muscle biopsy. These findings indicate that a neurogenic lesion affecting at least the peripheral sensory system is present at an early stage of Welander's distal myopathy and that the neurogenic lesion might precede the myopathic changes.

Adult

Peripheral administration of a long-chain fatty alcohol promotes septal cholinergic neurons survival after fimbria-fornix transection.

Peripherally administered n-hexacosanol, a long-chain fatty alcohol, strongly attenuated the degeneration of cholinergic neurons in the medial septum and the vertical limb of the diagonal band of Broca following transection of their dorsal projection to the hippocampus by unilateral fimbria-fornix aspiration. The maintenance of AChE-positive neurons was particularly striking in the vertical limb of the diagonal band of Broca, where 83% of the neurons survived after two weeks of n-hexacosanol treatment compared to 51% in the non-treated animals. This compound has already been found to possess some neurotrophic activities on cultured neurons from rat cerebral cortex. But the present study is the first report of an in vivo neurotrophic influence exerted by an exogenously administered long-chain fatty alcohol. The low dosage needed and the peripheral administration of this compound may be of great advantage in the reduction of cell loss in some neurodegenerative disorders like Alzheimer's disease or stroke.

Acetylcholinesterase

Walking efficiency before and after long-term muscle stretch in patients with spastic paraparesis.

Eight patients with stationary, spastic paraparesis were treated with long-term stretch of the hip adductor muscles to improve walking ability. Gait pattern, walking speed and perceived exertion of walking were assessed. Walking efficiency was assessed before and after treatment by measuring oxygen consumption and blood lactate level. After treatment walking pattern was improved. Perceived exertion decreased but walking speed was unchanged. Oxygen cost directly after treatment was lower in six patients, unchanged in one and higher in one. In the patient with unchanged oxygen cost the blood lactate level decreased, probably due to decreased recruitment of fast, type II muscle fibres. Blood lactate was unchanged in the other patients. When assessing walking ability, measurement of energy cost was found to be a valuable supplement to clinical judgement, but in spastic patients both oxygen cost and blood lactate must be considered.

Aged

Neurogenic involvement in distal myopathy (Welander). Histochemical and morphological observations on muscle and nerve biopsies.

Patients with distal myopathy (Welander) were subjected to muscle biopsy from the anterior tibial muscle (n = 4) and to nerve biopsy from the sural nerve at the ankle (n = 5) in order to elucidate a possible neurogenic component of the disease. The type I muscle fibres had a larger mean cross-sectional area as compared to normal controls and an increased variation in fibre size with both hypertrophic and atrophic fibres in one and the same biopsy. A normal muscle fibre type composition was found in the patients. Structural muscle fibre abnormalities such as atrophic fibres, mainly angulated, split fibres, rimmed vacuoles and centrally located nuclei were found in all biopsies. A disorganization and loss of myofibrils as well as autolytic vacuoles were the most prominent findings at the ultrastructural level. Two patients had a moderate loss of myelinated sural nerve fibres. The mean nerve fibre density was decreased as compared to normal controls while the mean nerve fibre area and circular diameter were increased due to selective loss of small diameter (A-delta) nerve fibres. The muscle and nerve fibre abnormalities are discussed with reference to neuropathic and myopathic changes. Some muscle fibre abnormalities are typical for a neurogenic disorder while some others are mostly seen in myopathies but may also appear in neurogenic conditions. A neurogenic etiology in Welander distal myopathy is further supported by the finding of loss of small diameter nerve fibres in the sural nerve.

Adult

Measurement of the subcutaneous fat in the distal forearm by single photon absorptiometry.

The influence of subcutaneous fat on single photon (125I) absorptiometry (SPA) measurement of bone mineral content of the distal forearm was investigated. A fat correction model was tested by measurements on eight lean subjects with different amounts of porcine fat around their forearm, and further validated from measurements on 128 females. In addition, it is shown that the fat content in the distal forearm can be measured by SPA with a short-term precision at 1.9% in an obese subject and that it correlates well with total body fat (r2 = .7) measured by dual photon absorptiometry, skinfold thickness (r2 = .5), and body mass index (r2 = .6). By using this method in a double-blind placebo-controlled trial, hormonal substitutional therapy significantly decreased the forearm fat content without affecting the body weight in postmenopausal osteoporotic women.

Adipose Tissue

Motoneuron firing and isomyosin type of muscle fibres in prior polio.

In patients with prior polio there was an excessive use of remaining motor units and an absence of type II muscle fibres in the tibialis anterior (TA). In the present study, eight subjects with prior polio with more than 90% type I fibres in the TA were examined. The aim was to elucidate whether the lack of type II muscle fibres was due to a selective loss of motoneurons with high threshold and high axonal conduction velocity or due to a muscle fibre transition from type II to type I. There was no decrease of the proportion of motoneurons with high threshold and high axonal conduction velocity. Monoclonal antibodies against fast and slow myosin heavy chains (MHC) were used as histochemical markers and many muscle fibres of type I according to ATPase stainability showed a binding of both anti-fast and anti-slow MHC. It is suggested that the type I muscle fibre dominance in prior polio subjects with excessive use of TA during walking is due to a muscle fibre transition from type II to type I and not to a loss of one class of motor units.

Adult

Effects of excessive use of remaining muscle fibers in prior polio and LV lesion.

Twenty-three subjects with weakness of musculus tibialis anterior (TA) due to prior poliomyelitis (n = 19) or prior LV lesion (n = 4) were examined regarding the use of remaining TA motor units during walking and the consequences of long-term overuse for the TA muscle fibers. Subjects with an excessive overuse exhibited almost only type 1 muscle fibers and with marked hypertrophy. Subjects who did not use remaining TA fibers because of too-severe paralysis had a normal fiber type differentiation and fiber atrophy. The use of remaining TA motor units was correlated to the type 1 muscle fiber percentage (r = 0.69) and to the type 1 fiber size (r = 0.78). Identical changes were observed in subjects with prior poliomyelitis and in subjects with prior LV lesion and were, thus, not specific for poliomyelitis. The changes in fiber type composition may be explained by a transition of type 2 to type 1 muscle fibers in accordance with previously reported experimental transneuronal stimulation through implanted electrodes in animals.

Adolescent

PET determination of regional cerebral glucose metabolism in alcohol-dependent men and healthy controls using 11C-glucose.

Regional brain glucose metabolism was determined in 9 male alcohol-dependent inpatients and 12 male healthy controls. All the patients were socially impaired by the alcohol abuse. All the subjects had abstained from alcohol and drugs for more than four weeks before entering the study. Brain glucose metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Regions of interest were drawn on displayed computed tomographic (CT) images of the brain. Regions were transferred to corresponding PET slices, allowing the determination of regional glucose metabolism. In the healthy volunteers there was a reduction in glucose metabolism with age. In 11 of the 19 brain regions examined, the alcoholics had a 20% to 30% lower glucose metabolism than the controls. This was true for both cortical and subcortical structures. The distribution of relative regional metabolic rates indicated that parietal cortical areas were most affected. Atrophic changes as shown by CT were not correlated to the reduced metabolism in the alcohol-dependent patients.

Adult

Neurotrophic effect of naturally occurring long-chain fatty alcohols on cultured CNS neurons.

A long-chain fatty alcohol,n-hexacosanol, that we have isolated from the Far-Eastern traditional medicinal plant, Hygrophila erecta, Hochr., is shown to promote the maturation of central neurons. Added at 500 nM to fetal rat brain neurons in culture, it increased both neurite outgrowth by a factor of 4-6 and the number of collaterals, especially in multipolar neurons. The biochemical differentiation of cultured neurons was also strikingly enhanced by this compound: it increased the protein content and almost doubled the activities of two neuron-specific enzymes, phosphate-activated glutaminase and neuron-specific enolase, by 92 and 78%, respectively. Extensive studies with several synthetic long-chain fatty alcohols showed that the neurotrophic activity was maximal for n-hexacosanol. It is suggested that some long-chain fatty alcohols with an appropriate length of hydrocarbon chain might play an important role in central neuron development.

Animals