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Biomedical subjects

J D Porter

Publications and source records attributed to J D Porter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Eyelid kinematics following blepharoplasty.

PURPOSE: This study characterizes the effects of blepharoplasty on blink dynamics in subjects with dermatochalasis. The authors evaluate the hypothesis that orbicularis oculi removal and the consequent alterations in blink are potentially harmful consequences of blepharoplasty. METHODS: Sixteen patients were studied, before and after laser blepharoplasty, by a modified scleral search coil technique. Changes in lid position during blinks were recorded before surgery as well as 2 months, and 1 year postoperatively. Off-line analyses assessed blink down-phase amplitude, peak velocity, duration, and main sequence (peak velocity versus amplitude) relationships. RESULTS: Despite muscle resection, there was no significant compromise of mean blink down-phase amplitude, peak velocity, or main sequence following blepharoplasty. Mean blink duration was likewise unchanged at either follow-up session from the preoperative state. Our data show that upper lid blepharoplasty does not cause any lasting decrement in lid function in blinking. CONCLUSIONS: Blepharoplasty includes resection of a portion of the orbicularis oculi. It appears unlikely that the purposeful resection of preseptal portion of the orbicularis oculi that accompanies blepharoplasty is responsible for any functional complications such as dry eye.

Adult↗
PubMed1999

Tuberculosis control and directly observed therapy from the public health/human rights perspective.

Directly observed therapy, short course (DOTS) is the current international strategy for controlling tuberculosis. Decisions have been taken internationally about the increasing tuberculosis epidemic-what to do and why to do it. But do we know bow the DOTS strategy can be implemented most appropriately and what changes need to be made to ensure that it is effective? This paper uses the Public Health/Human Rights framework to discuss TB control from a human rights rather than the biomedical perspective. The aim is to introduce different approaches to the current DOTS strategy in order to find more effective and appropriate ways to treat and care for people with tuberculosis. The paper argues that key dimensions of social, economic and physical access to TB services need to be assessed and accounted for in programme design. This will require that TB control adopt a wider interdisciplinary and multisectoral perspective to complement the current biomedical orientation.

Communicable Disease Control↗
PubMed1999

Sputum examination for acid-fast bacilli in private laboratories, Kathmandu Valley, Nepal.

OBJECTIVE: To investigate the characteristics of private laboratories and the process of sputum examination for acid-fast bacilli (AFB). DESIGN: A door-to-door survey of private laboratories in an urban municipality of Kathmandu valley was conducted during the first quarter of 1998. Semi-structured interviews were conducted with staff of 14/20 (70%) identified laboratories. RESULTS: All 14 private laboratories conducted sputum examination for AFB. The majority (71%) of staff lacked special training for AFB examinations. Monocular microscopes were commonly used (36%). Reagents were prepared irregularly, without quality control, and kept for as long as they lasted, often up to 4-6 months (43%). Laboratory registers were usually present (86%), but lacked information on patient's address and the purpose of the test. A median of 12.5 slides per laboratory had been examined during the previous month (range 0-70). A total of 235 AFB slides were examined, of which 18 (7.7%) were reported as positive. CONCLUSION: AFB examinations were widely available. Lack of training and quality control suggest a variable standard of AFB test results. It is recommended that the National Tuberculosis Programme (NTP) provide support and quality control to two to three (i.e., one for every 10) private laboratories in the area to secure private doctors' confidence in sputum testing.

Humans↗
PubMed1998

Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.

BACKGROUND: A randomized double-blind placebo-controlled trial was conducted to estimate the efficacy of preventive therapy for tuberculosis (TB) in HIV-infected adults in Lusaka, Zambia. The main outcome measures were the incidence of TB, mortality and adverse drug reactions. METHODS: During a 2 year period, 1053 HIV-positive individuals without evidence of clinical TB were randomly assigned to receive 6 months of isoniazid twice a week (H), or 3 months of rifampicin twice a week (R) plus pyrazinamide (Z), or a placebo. Therapy was taken twice a week and was self administered. Subjects presenting with symptoms during the follow-up period were investigated for TB. RESULTS: The 1053 subjects in the study were followed up for a total of 1631 person-years (median = 1.8 years). Twenty-nine subjects were taken off treatment as a result of adverse drug reactions. A total of 96 cases of TB/probable TB (59 TB and 37 probable TB) were diagnosed during the study period and 185 deaths were reported. One hundred and fifteen subjects (11%) did not return to the study clinic at any time after enrolment. The incidence of TB was lower in those subjects on preventive therapy (H and RZ groups combined) compared with those on placebo (rate ratio = 0.60, 95% CI: 0.36-1.01, P = 0.057), as was the incidence of TB/probable TB (rate ratio = 0.60, 95% CI: 0.40-0.89, P = 0.013). The effect of preventive therapy was greater in those with a tuberculin skin test (TST) of 5 mm or greater, in those with a lymphocyte count of 2x10(9)/l or higher, and in those with haemoglobin of 10 g/dl or higher. There was no difference in mortality rates between the preventive therapy and placebo groups. The effect of preventive therapy declined after the first year of the study so that by 18 months the rates of TB in the treated groups were similar to that in the placebo group. CONCLUSION: This study has demonstrated that preventive therapy with either twice weekly isoniazid for 6 months or a combination of rifampicin and pyrazinamide for 3 months reduced the incidence of TB in HIV-infected persons in Zambia. No effect was observed on mortality. The effect was greatest in persons who had a positive TST or a lymphocyte count of 2x10(9)/l or greater, indicating that preventive therapy may be more effective in people with less advanced immunosuppression. The limited duration of the protective effect reported in this study raises the question of the need for lifelong preventive therapy or re-prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1998

The distribution of primary afferent terminals from the eyelids of macaque monkeys.

Trigeminal sensory afferents from the eyelids convey two types of information that are important for the blink reflex. Movement of the lashes activates low-threshold mechanoreceptors which evoke protective blinks. Information about eyelid position is also transmitted centrally and is used to adapt the metrics of the blink reflex to changing conditions over time. This study employed transganglionic transport of horseradish peroxidase conjugated to choleratoxin-B subunit or wheat-germ agglutinin to investigate trigeminal afferents supplying the eyelids of macaque monkeys. Ganglion cells labeled from upper- and lower-lid injections were located in the ophthalmic and maxillary portions of the trigeminal ganglion, respectively. In both cases, labeled terminals were observed ipsilateral to the injected eyelid in the principal and spinal trigeminal nuclei. However, only a few labeled terminals were present in the principal nucleus, and very sparse terminal labeling was confined to a few locations along the ventral border of the pars oralis and interpolaris of the spinal trigeminal nucleus. The main concentration of label was found in the pars caudalis at and immediately below the spinomedullary junction. The terminal field from the upper eyelid was located ventrally in the pars caudalis, and that from the lower eyelid was located more dorsally. In both cases, the labeled terminal field was densest within lamina II of the spinal trigeminal nucleus. The heavy concentration of eyelid central terminals at the spinomedullary junction is surprising in light of physiological studies indicating representation of all parts of the face throughout the trigeminal nucleus. The distribution of eyelid afferent terminals in the macaque is caudal to the main concentration of corneal afferent terminals at the pars interpolaris/caudalis border. This may be a basis for differences seen in blinks produced by corneal as opposed to supraorbital stimulation. The presence of a single major site of eyelid primary afferent terminals suggests that sensory input for both eyelid proprioception and blink-reflex activation passes through this segment of the spinal trigeminal nucleus. These results provide a basis for investigation of the central connections of pars caudalis neurons in order to better establish the pathways producing trigeminally evoked blinks and blink adaptation.

Adaptation, Physiological↗
PubMed1998

Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing.

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested the hypothesis that the maintenance of calcium homeostasis is mechanistic in extraocular muscle protection. Atomic absorption spectroscopy has demonstrated a strong correlation between the perturbation of calcium homeostasis in hindlimb muscle that is severely damaged and the absence of changes in calcium in extraocular muscle. If, as in other skeletal muscles, extraocular muscle fibers are destabilized by merosin deficiency, we would expect an increase in total muscle calcium coupled with an adaptive response in the high capacity/speed of the sarcoplasmic reticulum of the eye muscle. However, we have not observed the expected increases in total muscle calcium content, Ca2+-ATPase activity, Na+/Ca2+ exchanger content, or smooth ER Ca2+-ATPase content that are predicted by this model. Instead, these results indicate that the increased membrane permeability that characterizes, and is potentially mechanistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calcium-scavenging systems are not primarily responsible for extraocular muscle protection in muscular dystrophy.

Animals↗
PubMed1998

Efficacy of gold weight implants in facial nerve palsy: quantitative alterations in blinking.

Deficient eyelid closure is a major visual threat to patients with unresolved facial nerve palsy. Gold weight implants assisted eyelid closure in patients with paresis of the orbicularis oculi, ameliorating patient complaints of dry eye, excessive tearing, and corneal epithelial breakdown. We used dynamic measures to assess the efficacy of upper eyelid gold weight implantation surgery for facial nerve palsy. The search coil technique was used to record spontaneous blinks bilaterally in six patients, before and after unilateral gold weight implantations into the upper eyelid in severe facial nerve palsy. In uncomplicated facial nerve palsy, the amplitude of blink down-phases for the paretic eyelid was 28.6 +/- 5.7% of the amplitude of the contralateral, normal eyelid. Following corrective surgery, closure of the paretic eyelid improved to 42.6 +/- 7.5% (P < 0.05). There was not a commensurate increase in the peak velocity of blink down-phases, suggesting that gold weight effects are mediated by a passive improvement in blink dynamics.

Adult↗
PubMed1998

Commentary: extraocular muscle sparing in muscular dystrophy: a critical evaluation of potential protective mechanisms.

Muscles or muscle groups exhibiting responses to neuromuscular disease that are unlike those of other skeletal muscles may provide novel information about pathogenesis leading to improved treatment strategies. The author's laboratory studies the relationship between the unique phenotype of the extraocular muscles and their selective sparing or targeting in neuromuscular disease. This commentary evaluates the evidence for and against four hypotheses for the selective protection of extraocular muscle in Duchenne muscular dystrophy (DMD) and merosin-deficient congenital muscular dystrophy (CMD).

Adaptation, Physiological↗
PubMed1998

Nitric oxide inhibits rhinovirus-induced cytokine production and viral replication in a human respiratory epithelial cell line.

To better understand the early biochemical events that occur in human rhinovirus (HRV) infections, we examined the kinetics and mechanisms of interleukin-8 (IL-8) and IL-6 production from infected epithelial cells. Several HRV strains caused IL-8 and IL-6 production, but HRV-16 induced maximal IL-8 and IL-6 mRNA expression and protein production more rapidly than did HRV-14, despite similar rates of replication of the two viral strains. Viral induction of cytokine mRNA does not require new protein synthesis, since it was unaffected by cycloheximide treatment. The potent glucocorticoid budesonide did not affect viral replication or cytokine mRNA induction but modestly inhibited cytokine protein production. Interestingly, the nitric oxide donor 3-(2-hydroxy-2-nitroso-1-propylhydrazino)-1-propanamine (NONOate) inhibited both rhinovirus replication and cytokine production in a dose-dependent fashion without reducing levels of cytokine mRNA. The NONOate effects were due to release of nitric oxide, because NONOate that had been depleted of its nitric oxide content had no effect. Thus, nitric oxide may play an important anti-inflammatory and antiviral role in colds and nitric oxide donors may represent a novel therapeutic approach.

Cell Line↗
PubMed1998

Visual system maldevelopment disrupts extraocular muscle-specific myosin expression.

The genetic and epigenetic influences that are responsible for the establishment and maintenance of the unique phenotype of the extraocular muscles (EOMs) are poorly understood. A role for visual cues in shaping EOM maturation was assessed in rats by using two visual deprivation paradigms, dark rearing and monocular deprivation. Isoforms of the contractile protein myosin heavy chain (MHC) were used as an index of phenotypic change in developing and adult EOMs after these visual insults. In rats that were dark reared during the visual critical period, the proportion of EOM fibers expressing either fast or slow MHCs was decreased significantly. EOM-specific myosin was also sensitive to dark rearing during the critical period, as evidenced by a significant decrease in its mRNA in EOMs from these rats. EOM-specific MHC did not change in either dark-reared rats returned to normally illuminated conditions or in adult rats denied visual experience for a similar time period. These data suggest that there may be a critical period during development when alterations in visual activity have significant consequences for the eye muscle phenotype. In contrast to dark rearing, monocular deprivation had a minimal effect on expression of the typical myosin isoforms and no effect on EOM-specific myosin expression. Collectively, these data confirm the hypothesis that visual input to the oculomotor system during development modulates EOM-specific MHC expression.

Animals↗
PubMed1998

The sparing of extraocular muscle in dystrophinopathy is lost in mice lacking utrophin and dystrophin.

The extraocular muscles are one of few skeletal muscles that are structurally and functionally intact in Duchenne muscular dystrophy. Little is known about the mechanisms responsible for differential sparing or targeting of muscle groups in neuromuscular disease. One hypothesis is that constitutive or adaptive properties of the unique extraocular muscle phenotype may underlie their protection in dystrophinopathy. We assessed the status of extraocular muscles in the mdx mouse model of muscular dystrophy. Mice showed mild pathology in accessory extraocular muscles, but no signs of pathology were evident in the principal extraocular muscles at any age. By immunoblotting, the extraocular muscles of mdx mice exhibited increased levels of a dystrophin analog, dystrophin-related protein or utrophin. These data suggest, but do not provide mechanistic evidence, that utrophin mediates eye muscle protection. To examine a potential causal relationship, knockout mouse models were used to determine whether eye muscle sparing could be reversed. Mice lacking expression of utrophin alone, like the dystrophin-deficient mdx mouse, showed no pathological alterations in extraocular muscle. However, mice deficient in both utrophin and dystrophin exhibited severe changes in both the accessory and principal extraocular muscles, with the eye muscles affected more adversely than other skeletal muscles. Selected extraocular muscle fiber types still remained spared, suggesting the operation of an alternative mechanism for muscle sparing in these fiber types. We propose that an endogenous upregulation of utrophin is mechanistic in protecting extraocular muscle in dystrophinopathy. Moreover, data lend support to the hypothesis that interventions designed to increase utrophin levels may ameliorate the pathology in other skeletal muscles in Duchenne muscular dystrophy.

Animals↗
PubMed1997

Absence of oculomotor and trochlear motoneurons leads to altered extraocular muscle development in the Wnt-1 null mutant mouse.

Wnt-1 null mutant mice lack midbrain somatic motor nuclei. Primordial migration and spatial patterning of the extraocular muscles, however, was preserved, but myogenesis was disrupted in aneural muscles. Some muscles normally innervated by oculomotor and trochlear nuclei received aberrant innervation, which proved sufficient to maintain prenatal stages of myogenesis. The absence of motoneurons followed by innervation from inappropriate motoneuron pools is a viable candidate mechanism in ocular motility disorders, including Duane retraction syndrome and congenital fibrosis of extraocular muscle.

Alleles↗
PubMed1997

The role of blink adaptation in the pathophysiology of benign essential blepharospasm.

OBJECTIVE: To investigate eyelid movements in patients with benign essential blepharospasm (BEB), with an emphasis on the characterization of the kinematics of normal and spastic blinks, assessment of interocular differences, and further delineation of the role of adaptive blink mechanisms in eyelid movement disorders. PATIENTS AND METHODS: The electromagnetic search coil technique was used to record the metrics of blinks bilaterally in 5 patients with untreated BEB. Eyelid kinematics and the main-sequence (peak velocity vs amplitude) relationships were analyzed. RESULTS: Patients with BEB exhibited a decrease in blink amplitude and peak velocity. Moreover, the main-sequence slope was decreased bilaterally. Spasms were bilateral and relatively conjugate. There was no change in the coordination of normal blinking across the 2 eyelids. CONCLUSIONS: These data demonstrate the operation of the adaptive regulation of blinking in an eyelid movement disorder. The findings suggest that the adaptive regulation of blink is a bilateral event. Blink-adaptive control systems can act on the blink reflex excitability and main-sequence relationships, changing these either together or independently. The hyperexcitable blink reflex of BEB is met by what is believed to be an adaptive decrease in the main-sequence slope that would decrease the strength of debilitating spasms. Collectively, these data extend the knowledge of the pathophysiology of BEB and, perhaps more important, establish the role of blink system plasticity in eyelid movement disorders.

Adaptation, Physiological↗
PubMed1997

Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles.

Congenital fibrosis of the extraocular muscles is an autosomal dominant congenital disorder characterized by bilateral ptosis, restrictive external ophthalmoplegia with the eyes partially or completely fixed in an infraducted (downward) and strabismic position, and markedly limited and aberrant residual eye movements. It has been generally thought that these clinical abnormalities result from myopathic fibrosis of the extraocular muscles. We describe the intracranial and orbital pathology of 1 and the muscle pathology of 2 other affected members of a family with chromosome 12-linked congenital fibrosis of the extraocular muscles. There is an absence of the superior division of the oculomotor nerve and its corresponding alpha motor neurons, and abnormalities of the levator palpebrae superioris and rectus superior (the muscles innervated by the superior division of the oculomotor nerve). In addition, increased numbers of internal nuclei and central mitochondrial clumping are found in other extraocular muscles, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III. This report presents evidence that congenital fibrosis of the extraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system.

Abnormalities, Multiple↗
PubMed1997

The oculomotor periphery: the clinician's focus is no longer a basic science stepchild.

The study of the oculomotor periphery, the extraocular muscles and their orbital attachments, is undergoing a rapid expansion. This is an important progression for both basic and clinical communities as, for too long, the ophthalmologist has worked primarily in the periphery and the basic researcher has been occupied with study of the central components of the oculomotor system. From recent studies, it is clear that the morphology, cell and molecular biology, and genetics of the eye muscles and their corresponding motoneuron pools, and muscle attachments within the orbit are more complex than has heretofore been appreciated.

Animals↗
PubMed1997

Oxidative stress as a potential pathogenic mechanism in an animal model of Duchenne muscular dystrophy.

Dystrophin-deficiency results in degeneration of most, but not all, skeletal muscles. The mechanisms responsible for degeneration of limb muscle and sparing of extraocular muscle are not known. To address the notion that muscle pathology may be free radical-mediated, we evaluated antioxidant enzyme activities and lipid peroxidation products (TBARS) content in mdx and control mice. TBARS content and the activities of total superoxide dismutase, selenium dependent glutathione peroxidase, glucose-6-phosphate dehydrogenase and catalase were consistently higher in both affected and spared muscles of mdx mice. These data suggest that oxidative stress may be constitutively present in mdx muscle, but may not be the principal pathogenic mechanism. To further test the hypothesis of oxidative stress involvement in dystrophinopathies, control strain and mdx mice were subjected to chronic hyperoxia. The pattern of antioxidant enzyme activities and TBARS content from hyperoxic control strain mice was similar to that of normoxic mdx mice, suggesting that a similar level of oxidative stress was induced. In conclusion, this study has provided indirect evidence for oxidative stress in dystrophin-deficient muscle.

Animals↗