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Biomedical subjects

J D Porter

Publications and source records attributed to J D Porter.

At least 55 records · Page 3Linked to original sources
PubMed1997

Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial.

OBJECTIVES: To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya. SUBJECTS: Six hundred and eighty-four HIV-1-infected adults. MAIN OUTCOME MEASURES: Development of tuberculosis and death. RESULTS: Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12). CONCLUSIONS: Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

AIDS-Related Opportunistic Infections↗
PubMed1997

Maladaptive neural compensatory mechanisms in Bell's palsy-induced blepharospasm.

We described four patients with Bell's palsy and blepharospasm and evaluated potential mechanisms that may be responsible for an apparent association between the two disorders. Eyelid movements in spontaneous blinks were studied by the search coil technique in patients with this novel disorder. Kinematic analyses documented bilateral eyelid spasm subsequent to unilateral Bell's palsy. The temporal interval between the onset of palsy and onset of blepharospasm was highly variable (weeks to > 20 years). Changes in the relationship between spontaneous blink peak velocity and amplitude, the main sequence, shared features previously found in uncomplicated Bell's palsy and blepharospasm patients. Furthermore, as in patients with typical Bell's palsy and idiopathic blepharospasm, both normal blinks and spasms were conjugate in spite of interocular differences in blink amplitude/peak velocity. We suggest that there is a correlation between the eyelid palsy and subsequent blepharospasm, and have designated this potentially new disease entity as Bell's palsy-induced blepharospasm. We propose a two-stage model for Bell's palsy-induced blepharospasm in which blink adaptive systems may produce the maladaptive consequence of eyelid spasms.

Adult↗
PubMed1997

Age-related changes in human blinks. Passive and active changes in eyelid kinematics.

PURPOSE: The authors analyzed eyelid kinematics in normal aging subjects to test the hypothesis that eyelid movements exhibit age-related changes and that blink disorders prevalent among the elderly, in turn, represent an outcome of normal aging processes. METHODS: The electromagnetic search coil technique was used to study blinks in normal human subjects for each decade from 40 to 89 years. Blink metrics (amplitude, peak velocity, and duration), main sequence relationships, and conjugacy were assessed. RESULTS: Mean amplitude and peak velocity of blinks decreased with age for spontaneous blinks and, to a lesser extent, for voluntary blinks. Some but not all, of this decline could be attributed to a peripheral phenomenon, narrowed palpebral fissure width. The spontaneous blink down phase main sequence slope also declined with age. By contrast, blink rate and the coordination of movements of the two eyelids--blink conjugacy--exhibited no change. CONCLUSIONS: These data demonstrate that disorders of blink systems typically seen in persons 50 years of age or older occur on a background of normal age-dependent changes in eyelid kinematics. Alterations in main sequence slope imply the operation of central adaptive systems during aging. Reduction in main sequence slope is interpreted as a reduction in aggregate orbicularis oculi motoneuron activity. Such a central neurologic adjustment in the motor output of blink systems may serve to compensate for an age-related increase in blink reflex excitability. Compensatory reduction in the main sequence relationship may offset a potentially hyperexcitable blink reflex, thereby reducing the likelihood of disorders such as blepharospasm. The authors conclude that although there are changes in the kinematics of blinking with age, such changes do not necessarily predispose an aging population to eyelid motility disorders.

Adult↗
PubMed1996

Bell's Palsy-associated blepharospasm relieved by aiding eyelid closure.

The efficacy of the blink reflex is maintained by adaptive control mechanisms. We describe a 39-year-old woman with the rare complication of blepharospasm-like symptoms appearing contralateral to an eyelid weakened by facial nerve palsy. The hyperexcitable blink reflex may be a maladaptive consequence of adaptive systems but was not accompanied by an expected increase in main sequence slope. Eyelid spasms were eliminated by the implantation of a gold weight to assist closure of the paretic eyelid. We suggest that aiding closure of the weak eyelid in this case caused a reduction in blink system excitability via the same compensatory mechanisms that initially produced the eyelid spasm. Data also suggest that blink-adaptive systems act via changes in reflex excitability and/or main sequence relationships, and that these may be regulated either synergistically or independent of one another.

Adult↗
PubMed1996

The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units.

Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a. We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

Animals↗
PubMed1996

Spatial and temporal patterns of myosin heavy chain expression in developing rat extraocular muscle.

The present study describes transitions in myosin heavy chain expression in the extraocular muscles of rats between the ages of E17 and adult. The unique phenotype of the extraocular muscle is reflected in its fibre type composition, which is comprised by six distinct profiles, each defined by location (orbital versus global layer) and innervation pattern (single versus multiple terminals). During extraocular muscle myogenesis, developmental myosin heavy chains were expressed in both primary and secondary fibres from embryonic day E17 through the first postnatal week. At this time, the downregulation of developmental myosin heavy chain isoforms began in the global layer in a fibre type-specific manner, reaching completion only after the first postnatal month. By contrast, developmental isoforms were retained in the overwhelming majority of orbital layer fibres into adulthood and expressed differentially along the length of these fibres. Fast myosin heavy chain was detected pre- and postnatally in developing secondary fibres and in all of the singly innervated fibre types and one of the multiply innervated fibre types in the adult. As many as four fast isoforms were detected in maturing extraocular muscle, including the extraocular muscle-specific myosin heavy chain. Slow myosin heavy chain was expressed in primary fibres throughout development and in one of the multiply innervated fibre types in the adult. In contrast, the pure fast-twitch retractor bulbi initially expressed slow myosin heavy chain in fibres destined to switch to the fast myosin heavy chain developmental programme. Based upon spatial and temporal patterns of myosin heavy chain isoform transitions, we suggest that epigenetic influences, rather than purely myogenic stage-specific factors, are critical in determining the unique extraocular muscle phenotype.

Aging↗
PubMed1996

Mycobacteriosis and HIV infection: the new public health challenge.

Human immunodeficiency virus (HIV) infection alters the epidemiology of mycobacterial infections. In the industrialised world, this has led to an increase in severe illness associated with Mycobacterium avium-intracellulare complex (MAC) and, in the developing world, to doubling of tuberculosis cases in some countries in Sub-Saharan Africa. The interaction with Mycobacterium tuberculosis occurs when the CD4 count is relatively high (> 200) and tuberculosis (TB) is now the commonest presenting AIDS defining disease in Africa. In international public health terms the interaction between TB and HIV infection has led to the World Health Organisation declaring TB to be a global emergency. Both TB and HIV are diseases of poverty and the key to the reduction of incidence of both diseases is the improvement of socio-economic conditions. Other control methods are case finding and treatment, chemoprophylaxis and BCG vaccination. Finding active (sputum positive) case of tuberculosis and treating them is the function of TB control programmes in all countries, but poor adherence to medication has lead to low cure rates and increasing development of drug resistance. Resources are needed to improve adherence to medication and for research to improve diagnostic methods and treatment.

HIV Infections↗
PubMed1996

Muscles of a different 'color': the unusual properties of the extraocular muscles may predispose or protect them in neurogenic and myogenic disease.

The rules that govern many aspects of skeletal muscle structure and function are very different for the extraocular muscle allotype. The myoblast lineages present in the extraocular muscle primordia are permissive for generation of an unusually wide range of fiber types. The balance that is struck between genetic specification and activity dependent factors in shaping fiber phenotype to suit the demands of complex visuomotor systems is not yet well defined. Because skeletal muscle has high energy demands, diversity in fiber types is needed to maximize efficiency; greater diversity in fiber composition then indicates a more diverse functional repertoire. Together, the characteristics of small motor unit size, precise dependence of muscle force upon motor neuron discharge rate, high contractile speed but low tension development, and contractile protein heterogeneity contribute toward the high precision and diversity that is required for eye movements. Finally, the structural and functional characteristics and plasticity of the individual extraocular muscle fiber types play an important role in determining their response to disease or manipulation. The lack of uniform responses across the muscle allotypes in disease, or in response to pharmaceutical or surgical interventions, requires that we obtain a better understanding of the fundamental differences that exist between muscle groups.

Humans↗
PubMed1996

Kinematic analysis of eyelid movements in patients recovering from unilateral facial nerve palsy.

We assessed eyelid function by subjective clinical examination and quantitative means in patients recovering from facial nerve palsy. Electromagnetic search coil techniques were used to record the concurrent movements of the two eyelids to study alterations in blink main sequence (peak velocity versus amplitude) relationships and interocular differences in eyelid kinematics. After onset of unilateral palsy, the paresis of eyelid closure showed varying degrees of recovery. Adaptive increases in blink main sequence slope contributed to maximizing closure of the paretic eyelid. However, blink adaptation mechanisms must operate bilaterally, as there also was evidence of altered main sequence slope in the nonparetic eyelid. In general, main sequence slope was inversely related to the level of eyelid paresis. The highest indices of blink adaptation were in those patients with moderate paresis, and main sequence slope was decreased in those patients with increasing degrees of recovery. The assessment of eyelid function with search coil techniques provides a sensitive means of monitoring disease and treatment course. Data also aid understanding of adaptive gain control in the neural control of blink in health and disease.

Adaptation, Physiological↗
PubMed1996

Structure-function correlations in the human medial rectus extraocular muscle pulleys.

PURPOSE: Fibroelastic pulleys function like the trochlea to fix the position and pulling direction of the recti extraocular muscles within the orbit. This study characterized the fine structure of the human medial rectus muscle pulley. METHODS: Human medial rectus muscle pulley tissue was dissected at autopsy, immersed in aldehyde fixative solution, and processed for and examined with light and electron microscopy. RESULTS: Pulley structure were located within posterior Tenon's fascia, closely surrounding the medial rectus muscle. Pulleys were comprised of a dense collagen matrix with alternating bands of collagen fibers precisely arranged at right angles to one another. This three-dimensional organization most likely confers high tensile strength to the pulley. Elastin fibrils were interspersed in the collagen matrix. Fibroblasts and mast cells were scattered throughout the relatively acellular and avascular collagen latticework. Connective tissue and smooth muscle bundles suspended the pulley from the periorbita. Smooth muscle was distributed in small, discrete bundles attached deeply into the dense pulley tissue. CONCLUSIONS: Fine structural observations confirm the existence and substantial structure of a pulley system in association with the medial rectus extraocular muscle. The presence of pulleys must be considered in models of the oculomotor plant. The cytoarchitecture and placement of pulleys suggest that they are internally rigid structures and are consistent with the idea that they determine functional origins for the extraocular muscles. However, the nature of the connective tissue-smooth muscle struts suspending the pulley system to the orbit supports the notion that the pulley position, and thus the vector force of the eye muscles, may be adjustable.

Biomechanical Phenomena↗
PubMed1996

Extraocular, limb and diaphragm muscle group-specific antioxidant enzyme activity patterns in control and mdx mice.

The mechanisms primarily responsible for the degenerative processes occurring in dystrophic skeletal muscle remain unresolved. The identification of the mechanisms that lead to the complete sparing of extraocular muscle in dystrophinopathies is of particular interest. A number of studies have provided evidence to suggest that the muscle pathology that characterizes muscular dystrophy may be, in part, free radical mediated. In the present study, we examined the antioxidant enzyme status of extraocular, diaphragm and gastrocnemius muscles in control strain and mdx mice. Our results revealed that in the control strain, both extraocular and diaphragm muscles had higher copper/zinc superoxide dismutase, manganese superoxide dismutase and selenium dependent glutathione peroxidase activities as compared to the gastrocnemius. Furthermore, the diaphragm had higher glutathione reductase activity as compared to the gastrocnemius. These findings indicate that the highly aerobic extraocular and diaphragm muscles have higher antioxidant enzyme capacity than the gastrocnemius, a muscle more dependent on anaerobic energy metabolism. Changes in the antioxidant enzyme status of the mdx mouse correlated, in part, with the degree of histopathological involvement of the three muscle groups assessed.

Animals↗
PubMed1994

Aberrant reinnervation of facial musculature in a subhuman primate: a correlative analysis of eyelid kinematics, muscle synkinesis, and motoneuron localization.

A macaque monkey with a preexisting facial nerve injury showed a synkinesis of perioral muscles with blinking and thus provided a serendipitous model for a multiphasic analysis of this common neurologic syndrome. The amplitude of the paretic eyelid in spontaneous and air-puff-induced blinks was about one-third that of the normal eyelid. Despite the blink hypometria, induced blink durations remained matched for the two lids. EMG confirmed co-contraction of the zygomaticus and orbicularis oculi muscles on the affected side during blinking, with silence of the zygomaticus on the normal side. Neuroanatomic investigation showed that, on the affected side, some zygomaticus motoneurons were in the somatotopically correct nuclear subdivisions but that the majority were in the dorsal subdivision, which normally innervates the orbicularis oculi. This study supports the contention that some orbicularis oculi motoneurons are incorrectly rerouted to supply the perioral musculature following recovery from a peripheral seventh-nerve injury. This same pattern of relative weakness in eyelid muscles and the stereotyped co-contraction of lid and perioral muscles with blinking occurs in humans, suggesting that aberrant reinnervation may be the mechanism for this clinical phenomenon.

Animals↗
PubMed1994

Conjugacy of spontaneous blinks in man: eyelid kinematics exhibit bilateral symmetry.

PURPOSE: To provide a quantitative description of the conjugacy of human eyelid movements during spontaneous blinks. METHODS: Eyelid movements occurring during spontaneous blinks were recorded bilaterally using a modification of the electromagnetic search coil technique. In off-line analyses, covariation of amplitude, peak velocity, and duration of blink down phases were determined for the two eyelids. Interocular differences in the timing of blink onset and offset, and time to peak velocity, also were evaluated. RESULTS: Human blink motor control systems act to link tightly the spatial and temporal characteristics of movements of the two eyelids. Data show that human spontaneous blinks are conjugate. Analysis of interocular covariation of blink amplitude, peak velocity, and duration yielded linear functions with high correlation coefficients. Interocular comparison of eyelid movement durations during blinks showed a particularly high correlation. There were negligible interocular differences in blink down-phase onset time, termination time, and time to peak velocity. A small percentage of blinks exhibited interocular differences in amplitude and peak velocity of > 20%; however, even in these cases, blink duration remained tightly linked. CONCLUSION: Spatial and temporal properties of eyelid movements occurring during spontaneous blinks are conjugate. These data support the hypothesis that a bilateral gating mechanism regulates blink duration. Elements downstream from the gate may differentially and unilaterally alter blink amplitude and peak velocity, but the duration of blinks remains time-locked for the two eyelids.

Adult↗
PubMed1993

Quantitative analysis of eyelid movement metrics reveals the highly stereotyped nature of monkey blinks.

Blink movement metrics were studied in three alert cynomolgus monkeys using electromagnetic search coils attached to the eyelids bilaterally. Monkey blinks averaged approximately 24 degrees. Down-phase peak velocities were approximately twice those of the corresponding up phases. Most blinks were symmetrical with close temporal linkage of onset and offset between the two eyelids. Monkey blinks exhibited higher peak velocities and shorter durations than have been previously described for similar amplitude movements in humans. Peak velocity vs. amplitude plots were linear and non-saturating within a 45 degrees range for both up and down phases. The relationship between blink peak velocity and average velocity was linear with a slope of approximately 2.0. These values were very similar to those obtained by others, not only for blinks, but also for saccadic eye and ballistic limb movements. Down-phase amplitude-duration behavior could be best described by a linear function with slope < 0.7, while amplitude-duration slope of up phases was best described by a second-order polynomial. Unlike saccadic eye movements, larger amplitude blinks are obtained primarily via increases in peak velocity rather than through extension of blink duration. These data provide mathematical descriptions of monkey blink behavior that indicate the stereotypical nature of blinks. This will serve as a normative data base with which to better understand the neural processing that goes into blinks and will allow the assessment of eyelid movement disorders and evaluation of potential treatments of these disorders.

Animals↗
PubMed1993

Survival of extraocular muscle in long-term organotypic culture: differential influence of appropriate and inappropriate motoneurons.

The myotrophic effects of a precise matching of motoneuron to target muscle may be particularly apparent during the development of some unique skeletal muscle types, such as the extraocular muscles. To understand how motoneuron-specific factors modulate muscle ontogeny, neonatal extraocular muscle explants were cocultured with either the appropriate midbrain motoneurons or the inappropriate spinal cord motoneurons. Thigh muscle cocultured with spinal motoneurons, which differentiates and survives for several months, served as a control. In short-term cultures (during the first 3 weeks in vitro), neonatal extraocular muscle explants developed myotubes that were immunoreactive for myosin, became innervated, and matured in parallel with hindlimb muscle explants. The origin of the motoneurons (midbrain or spinal cord) did not affect extraocular muscle development during the first 3 weeks in vitro. However, in long-term cultures (after the third week in vitro), extraocular muscle that was innervated by the inappropriate spinal motoneurons failed to survive and degenerated. The failure of extraocular muscle to survive when cocultured with the inappropriate motoneurons did not result from an artifact of in vitro conditions. When extraocular muscle primordia were innervated by midbrain explants, many of which contain oculomotor motoneurons, the cultures thrived for > 60 days. We conclude that the trophic requirements of extraocular muscle in organotypic culture are different from those of skeletal muscle isolated from the hindlimb. The novel oculomotor motoneuron-specific interactions that are essential for the survival of extraocular muscle primordia in vitro may prove to be important for the determination of the unusual properties of extraocular muscle in vivo.

Animals↗