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Biomedical subjects

J D Porter

Publications and source records attributed to J D Porter.

At least 73 records · Page 4Linked to original sources

Botulinum toxin paralysis of the orbicularis oculi muscle. Types and time course of alterations in muscle structure, physiology and lid kinematics.

In chronically prepared guinea pigs, we investigated the time course of botulinum toxin A's (Bot A) effect on the blink reflex by monitoring lid movements and EMG activity prior to and after Bot A injection into the orbicularis oculi muscle (OOemg), or after nerve crush of the zygomatic nerve. We correlated these alterations with the morphological changes of the orbicularis oculi (lid-closing) muscles of the same animals. After Bot A treatment there was a profound reduction of OOemg activity and blink amplitudes as well as a slowing of maximum blink down-phase velocity. Blink up-phases, however, remained unchanged. Gradual recovery of OOemg magnitude and blink amplitude started around day 6; a functioning blink reflex appeared on day 21, and full recovery of blink amplitude occurred by day 42. Crushing the zygomatic branch of the facial nerve produced similar changes in blink parameters, but recovery was much more rapid (15 days) than for Bot A-treated guinea pigs. The morphological analysis demonstrated that Bot A produced a denervation-like atrophy in the orbicularis oculi. No fiber type-specific alterations were noted, and all muscle fiber types ultimately recovered, with no longstanding consequences of the transient denervation. Our findings support the notion that functional recovery was the result of preterminal and terminal axonal sprouting that subsequently re-established functional innervation. Moreover, differences between the present findings and those seen after injection of Bot A into the extraocular muscles strongly support the hypothesis that the composition in terms of muscle fiber type and the properties of the motor control system of a given muscle greatly influence both how the particular muscle responds to toxin injection, and how effective the toxin is in resolution of neuromuscular disorders that affect a particular muscle. The present findings were consistent with clinical observations that Bot A produces only temporary relief in patients with essential blepharospasm. It is likely that the efficacy of Bot A in treatment of blepharospasm could be improved by using agents that suppress terminal sprouting. The close correspondence of the changes in blink physiology between human patients and guinea pigs after Bot A treatment demonstrate that the guinea pig is an excellent model system for testing strategies to prolong the beneficial effects of Bot A treatment in relieving lid spasms in human subjects.

Animals↗

Types and time course of the alterations induced in monkey blink movements by botulinum toxin.

The alterations induced in eyelid movement metrics subsequent to unilateral injections of botulinum toxin type A into the orbicularis oculi muscle were studied in chronic alert monkeys using the search coil technique. Botulinum toxin caused rapid paralysis of blinks in the treated eyelid. The amplitude and peak velocity of blinks generated by this eyelid remained at or below 20% of that of the fellow, untreated eyelid for 10-20 days. Blink amplitude gain increased linearly thereafter, attaining control values by 40-60 days after injection. Recovery of blink peak velocity was slower. The adaptive alterations in blink duration that were observed during the acute phase of toxin paralysis suggest that the mechanisms responsible for blink reflex plasticity may produce bilateral adjustments in eyelid function. Taken together, these data establish a quantitative data base that can be exploited in order to: (1) better understand the neural adaptive mechanisms that operate during eyelid movements and (2) allow quantitative comparisons between current treatment protocols that employ botulinum toxin and protocols that may lead to improvements in the treatment of chronic eyelid spasm (blepharospasm).

Animals↗

Somatosensory pressure affects immobility and grasping reactions in bilateral labyrinthectomized rats.

The effects of dorsal clip pressure and proprioceptive plate pressure to soles of the feet on tonic immobility; dorsal clip pressure on contact righting, horizontal bar, and vertical cling; forepaw and slope board grasp reactions were investigated in bilateral labyrinthectomized (BL) rats. Both dorsal and proprioceptive pressures potentiated the duration of tonic immobility in BL animals whereas only the dorsal pressure affected the controls. Dorsal pressure potentiated the duration of the horizontal bar, vertical cling, and slope board grasps in both the control and BL group. However, the behavioral patterns were different. The BL animals had weak grasp reactions and with the dorsal clip, emitted "head-back fall" during the vertical cling and slope board grasp conditions. The results were discussed in terms of the tactile and vestibular interactions and control on the postural mechanisms.

Animals↗

The value of wide-needle aspiration in the diagnosis of tuberculous lymphadenitis in Africa.

OBJECTIVES: To evaluate wide-needle (19-gauge) aspiration in the diagnosis of tuberculous lymphadenitis. SETTING: Department of Surgery, University Teaching Hospital, Lusaka, Zambia. PATIENTS: Three hundred and four patients presenting to one surgeon for diagnostic surgical biopsy of a peripheral lymph node during 1989-1990. DESIGN: Prospective study in which wide-needle aspiration routinely preceded open surgical biopsy. MAIN OUTCOME MEASURES: Histology and mycobacterial culture of the surgically biopsied lymph node; HIV-1 serology; successful aspiration of material, naked-eye appearance of aspirate, presence of acid-fast bacilli and/or microscopic caseation in the aspirate. RESULTS: One hundred and eighty-eight out of 304 (61.8%) patients had histologically and/or culture-proven tuberculous lymphadenitis, of whom 155 out of 183 (84.7%) tested HIV-1-seropositive. Material was successfully aspirated from 180 out of 188 (95.7%) of patients with proven tuberculous lymphadenitis. Macroscopic caseation, diagnosable on naked-eye examination alone of the aspirate, was present in 49 out of 120 (40.8%) consecutive aspirates from tuberculous nodes. Acid-fast bacilli and/or microscopic caseation were seen in 116 out of 155 (74.8%) aspirates from tuberculous nodes for which smears stained both by Ziehl-Nielsen and haematoxylin & eosin were available. CONCLUSIONS: It is recommended that all patients with suspected tuberculous lymphadenitis in Africa, undergo wide-needle aspiration before surgical biopsy or empirical treatment.

Adolescent↗

Diversity and developmental regulation of extraocular muscle: progress and prospects.

The developmental regulation of skeletal muscle phenotypes has attracted much attention from cell and molecular biologists. Myogenesis serves as an excellent model of the interaction of genetic and epigenetic events in determining definitive adult characteristics. The muscles that are responsible for eye movements are among the most structurally and functionally diverse mammalian skeletal muscles. Despite these unique attributes, the extraocular muscle has been studied less extensively than the traditional limb and diaphragm models. This review explores current concepts regarding the development of these muscles. Proper interocular alignment and coordination of eye movements are essential for normal vision in the adult. Moreover, coordinated oculomotor function during the perinatal period is critical for the normal development of the visual system. Therefore, a thorough understanding of the sequence of events and mechanisms that regulate extraocular muscle development and maldevelopment is vital. Studies related to myoblast origin and differentiation and to the role of genetic versus environmental factors in shaping and maintaining adult extraocular muscle phenotype are reviewed. Prospects for understanding the cellular and molecular mechanisms that regulate the heterogeneity and plasticity of these muscles also are discussed.

Animals↗

Interconnections between the primate cerebellum and midbrain near-response regions.

The goal of this study was to determine the pattern of the connections between the midbrain and cerebellum that may play a role in the modulation of the near-response in the macaque. Injection of the retrograde tracer wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the physiologically identified midbrain near-response region, which includes the supraoculomotor area, labelled cells throughout the deep cerebellar nuclei. However, labelled cells were particularly concentrated in the ventrolateral corner of the contralateral posterior interposed nucleus and in the contralateral and, to a lesser extent, the ipsilateral fastigial nuclei. Subsequently, injections of WGA-HRP were used to define the midbrain terminations of the deep cerebellar nuclei. Fastigial nucleus injections labelled terminals in a band along the border between the oculomotor nucleus and the supraoculomotor area that included the Edinger-Westphal nucleus. Injections of the posterior interposed nucleus labelled terminals in the portion of the supraoculomotor area dorsal to the fastigial projection and did not involve the Edinger-Westphal nucleus. In both cases, the terminal label was primarily found contralaterally. In contrast, retrogradely labelled cells were primarily found ipsilaterally within the supraoculomotor area following cerebellar injections. Retrogradely labelled cells projecting to the deep nuclei were also found bilaterally in the anteromedian nucleus, along with sparse terminal label. Taken as a whole, these results demonstrate the presence of a highly specific pattern of labelling in the supraoculomotor area, which may indicate that the posterior interposed nucleus and the fastigial nucleus play different roles in the control of the near-response. Alternatively, these projections may subserve other functions, such as modulating the pupillary light reflex. The fact that the projection from the deep nuclei is primarily contralateral, while the supraoculomotor projection to the deep nuclei is primarily ipsilateral, suggests that this may not be a simple feedback system, but may instead be involved in balancing the gains in the two eyes. In sum, physiological experiments have indicated the presence of near-response neurons in the midbrain supraoculomotor area and have indicated that the cerebellum may play a role in modulating the components of the near-response, as well as activity in the intrinsic eye muscles. The present experiments suggest a pattern of connections that might subserve this cerebellar modulation.

Animals↗

Lack of early antitoxin response to tetanus booster.

Tetanus immune globulin (TIG) continues to be recommended in persons with tetanus-prone wounds who have incomplete or unknown tetanus immunization status. The aim of this study was to determine whether, following a booster dose of tetanus toxoid in adults who had not been immunized in the previous 10 years, there was an antitoxin response to tetanus toxoid booster within 4 days. Thirty-one adults were investigated, baseline levels for tetanus antitoxin assayed using an ELISA technique, and an injection of adsorbed tetanus toxoid (0.5 ml) given. Blood samples for tetanus antitoxin levels were taken at daily intervals for the 4 days following immunization. Tetanus boosters following the primary course but before the present study did not significantly increase the levels of pre-study tetanus antitoxin and following the study booster there was no difference between the preboost levels and the levels on days 1 to 4. This finding indicates that the present recommendations for the use of TIG in tetanus-prone wounds are appropriate.

Adult↗

The laminar distribution of macaque tectobulbar and tectospinal neurons.

The superior colliculus exerts its most direct influence over orienting movements, and saccades in particular, via its descending projections to the brain stem and spinal cord. However, while there is detailed physiological data concerning the generation of saccade-related activity in the primate superior colliculus, there is relatively little data on the detailed connectivity of this structure in primates. Consequently, retrograde transport techniques were utilized to determine the locations of the cells of origin of these descending pathways in macaque monkeys. Tectal cells that projected to the ipsilateral pontine reticular formation were mainly found in the deep gray layer and occasionally in the intermediate gray layer. Tectal cells that projected to the contralateral pontine reticular formation were predominantly located in the intermediate gray layer. The contralaterally projecting population could be subdivided into two groups. The cells in upper sublamina of the intermediate gray layer project primarily to the saccade-related regions of the paramedian reticular formation. Cells in the lower sublamina project primarily to more lateral regions of the pontine reticular formation and to the spinal cord. We conclude that the primate colliculus is provided with at least three descending output channels, which are likely to differ in their connections and functions. Specifically, it seems likely that the lower portion of the intermediate gray layer may be specialized to subserve combined head and eye orienting movements, while the upper sublamina subserves saccades.

Animals↗

Prenatal morphogenesis of primate extraocular muscle: neuromuscular junction formation and fiber type differentiation.

Extraocular muscle represents a distinctive class among mammalian skeletal musculature in exhibiting the full range of muscle fiber type variability found in vertebrate species. To better understand the basis for the unique structural/functional diversity of extraocular muscle, the ontogeny of lateral rectus muscles was studied in Macaca nemestrina fetuses of 62-156 days gestation using light and electron microscopy. At E62, myotubes and myofibers are evident, but fiber-type differentiation has not yet occurred and neuromuscular junctions are primitive. By E92, presumptive singly and multiply innervated fiber types could be distinguished on the basis of myofibril delineation. Like other skeletal muscles, extraocular myogenesis proceeds through at least two generations of myofibers. All primary and secondary myofibers were generated and were maturing by E121. The phylogenetically "old" global multiply innervated fiber type was the first to attain adult form. This was followed by maturation of global layer singly innervated fiber types, which are developed by E156, except for attainment of definitive size and mitochondrial content. Orbital layer fiber types, particularly the orbital singly innervated fiber, are the last to mature. Neuromuscular junction maturation paralleled the changes observed during fiber-type differentiation. In summary, the sequential development of their constituent muscle fiber types may reflect the functional pressures the extraocular muscles are exposed to by maturing visual and visuomotor systems. In particular, ontogenic and phylogenic changes observed in the orbital singly innervated fiber type may have direct implications for the types, range, and precision of eye movements used by different species and at different gestational ages.

Animals↗

Tuberculosis in developing countries.

Every year, between six and eight million people worldwide develop tuberculosis and 2-3 million die of the disease. The situation is worsening due to the epidemic of human immunodeficiency virus (HIV) infection and reactivation of tuberculosis in patients with 'dual infection'. The World Health Organisation estimated that three million persons had 'dual infection' in 1990; 78% occurring in Africa. Tuberculosis, which affects adults during their most productive years and is a curable and preventable disease, has thus become a priority in the 1990s after a period of neglect. It also has some of the most cost effective health interventions available. The thrust of tuberculosis research in developing countries should be to support national tuberculosis control programmes, both in the development of their infrastructure and in research, to assist and develop tuberculosis control strategies.

AIDS-Related Opportunistic Infections↗

L-dopa-induced air-stepping in developing rats.

Rat pups at postnatal day (PN) 0, 5, 10, 15, and 20 were injected with 100 mg/kg L-3,4-dihydroxyphenylalanine (L-DOPA; s.c.) or the control vehicle and suspended in a sling. L-DOPA induced highly stereotyped air-stepping that varied along several dimensions across development. The latency to air-stepping was constant across age, but the duration was significantly shorter in the older pups. At all ages, air-stepping was preceded or accompanied by raising of the head and dorsiflexion of the tail. The rate of stepping increased across age and gait varied with age. At PN 0, L-DOPA induced alternating forelimb movements with little involvement of the hindlimbs. At PN 5 and 10, both forelimb and hindlimb alternation were observed. At PN 10 and 15 swimming-like behavior emerged, and at PN 10, 15, and 20, episodes of galloping were interspersed with limb alternation. Thus, highly coordinated activity can be elicited by L-DOPA at all ages studied when the rat pup needs not support its own body weight and has no contact with a substrate. Drug-induced air-stepping promises to be an important new paradigm for pharmacological and behavioral studies of the development of locomotor controls in mammals.

Animals↗

Botulinum-induced changes in monkey eyelid muscle. Comparison with changes seen in extraocular muscle.

Botulin type A was injected into the eyelids of adult monkeys, and structural alterations in the orbicularis oculi muscle were evaluated after survival times of 7 to 84 days. The most profound change seen at both the light- and electron-microscopic levels was nonselective atrophy of virtually all muscle fibers. Moreover, the botulin-induced blockade of neuromuscular transmission was nonspecific in producing alterations in the three orbicularis fiber types. Muscle structural changes appeared to be reversible, with no apparent long-term consequences. While sprouting of preterminal axons was noted in botulin-treated muscle, formation of collateral sprouts did not appear to be widespread. These changes contrast with the fiber type-specific, long-term alterations induced in extraocular muscle by botulin treatment. However, this differential response may be attributed to the very clear differences in fiber type composition and motor control mechanisms between eyelid and extraocular muscle groups. The efficacy of botulin treatments for strabismus and focal dystonia may then be directly related to both the anatomic fiber type composition and the functional properties of motor control systems of the injected muscle.

Animals↗

Ultrastructural changes in the masseter muscle of Macaca fascicularis resulting from intramuscular injections of botulinum toxin type A.

Intramuscular injections of botulinum toxin type A (Oculinum) is used to treat strabismus and focal dystonias affecting orofacial muscles. However, the toxin-induced morphological changes that underlie the therapeutic alterations of tone in the muscles of mastication have not been described. In this study, paired intramuscular injections of botulinum toxin (10 units) were made in three adult monkeys (Macaca fascicularis) allowed to survive 14, 28 and 63 days. Another monkey received multiple injection-pairs over 84 days. Animals were killed by deep pentobarbital anaesthesia before transcardiac perfusion-fixation. Tissue sampled from comparable regions of the injected masseter, the uninjected masseter and an uninjected animal was processed for ultrastructural analysis. Few changes were found 14 days post-injection. However, muscle fibres showed myofibrillar dissolution, aberrations in the Z-line, and enlarged mitochondria in the region of the I-band by 28 days. In the 63-day and 84-day animals, the injected muscle was considerably smaller than the uninjected, contralateral muscle. Regions of the injected muscle contained fibres with markedly reduced cross-sectional area. Internalization of myonuclei, loss of myofibrillar organization, and helical complexes were common. Toxin-induced changes, though similar to those that follow denervation by axotomy, were not accompanied by degeneration of neuromuscular junctions. Instead, morphological evidence for axonal sprouting in the region of the neuromuscular junction, possibly contributing to functional recovery, was seen as early as 14 days in toxin-treated muscles.

Actin Cytoskeleton↗

Outbreak of adenoviral infections in a long-term paediatric facility, New Jersey, 1986/87.

During an 8-week period in the winter of 1986-87, there were 11 deaths from an adenovirus infection (case fatality rate = 39%, 11/28) in a long-term care paediatric facility in southern New Jersey. Among the 61 resident children, all with severe congenital and/or acquired disabilities, 28 developed a febrile respiratory illness compatible with adenovirus infection [attack rate (AR) = 46%]. Patients with tracheostomies were three times as likely to become ill [relative risk (RR) = 3.2, 95% confidence intervals (CI) = 1.8-5.6]. Twenty-three members of the staff had a similar febrile illness (AR = 22%, 23/106); nurses were more likely to be ill than other staff (RR = 3.0, 95% CI = 1.1-11.4). Adenovirus 7 was isolated from four of the case patients and adenovirus 1 from one. The findings suggest prolonged transmission between patients and nursing staff with lack of cohorting of ill patients probably contributing to the prolongation of the outbreak. This investigation indicates that adenoviral outbreaks, although rare, can have a high mortality in severely disabled children, and that future outbreak investigations should examine the use of vaccines or antiviral agents to reduce mortality and for outbreak control.

Adenovirus Infections, Human↗