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Biomedical subjects

J D Porter

Publications and source records attributed to J D Porter.

At least 19 recordsLinked to original sources
PubMed2005

Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource-poor settings?

OBJECTIVES: To explore patient and health worker perspectives on adherence to tuberculosis preventive therapy (TBPT), and to derive lessons for improving access to care amongst human immunodeficiency virus (HIV) infected individuals in resource-poor settings. DESIGN: Both quantitative and qualitative methods were employed. Patient records were reviewed for HIV-positive individuals attending a hospital-based HIV clinic between January 2000 and March 2002. Eighteen patients and two health care workers underwent in-depth interviews exploring perspectives around adherence. RESULTS: Of 229 HIV-positive clinic attendees, 94 (41.0%) were eligible for TBPT. Of 87 patients initiating a 6-month TBPT course of isoniazid 300 mg daily, 41 (47.1%) completed TBPT. Of the 46 interrupters, 16 (34.7%) did not return to the clinic after receiving their first dose of TBPT. Barriers to adherence included fear of stigmatization, lack of money for food and transport, the belief that HIV is incurable, competition between Western and traditional medicine, and a reluctance to take medication in the absence of symptoms. Disclosure of HIV status, social and family support, and a supportive clinic environment positively influenced adherence. CONCLUSION: Interventions to improve the accessibility and quality of the care delivery system have the potential to support adherence to TBPT and other HIV care regimens, including antiretroviral therapy.

Adult↗
PubMed2001

Extraocular muscle is defined by a fundamentally distinct gene expression profile.

Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few conserved muscle fiber types, some, typically craniofacial, muscles exhibit fiber types that appear to lie outside the common phenotypic range. We analyzed gene expression profiles of three putative muscle classes, limb, masticatory, and extraocular muscle (EOM), in adult mice by high-density oligonucleotide arrays. Pairwise comparisons using conservative acceptance criteria identified expression differences in 287 genes between EOM and limb and/or masticatory muscles. Use of significance analysis of microarrays methodology identified up to 400 genes as having an EOM-specific expression pattern. Genes differentially expressed in EOM reflect key aspects of muscle biology, including transcriptional regulation, sarcomeric organization, excitation-contraction coupling, intermediary metabolism, and immune response. These patterned differences in gene expression define EOM as a distinct muscle class and may explain the unique response of these muscles in neuromuscular diseases.

Animals↗
PubMed2001

Extraocular muscle is spared despite the absence of an intact sarcoglycan complex in gamma- or delta-sarcoglycan-deficient mice.

Models of the dystrophin-glycoprotein complex do not reconcile the novel sparing of extraocular muscle in muscular dystrophy. Extraocular muscle sparing in Duchenne muscular dystrophy implies the existence of adaptive properties in these muscles that may extend protection to other neuromuscular diseases. We studied the extraocular muscle morphology and dystrophin-glycoprotein complex organization in murine targeted deletion of the gamma-sarcoglycan (gsg(-/-)) and delta-sarcoglycan (dsg(-/-)) genes, two models of autosomal recessive limb girdle muscular dystrophy. In contrast to limb and diaphragm, the principal extraocular muscles were intact in gsg(-/-) and dsg(-/-) mice. However, central nucleated, presumptive regenerative, fibers were seen in the accessory extraocular muscles (retractor bulbi, levator palpebrae superioris) of both strains. Skeletal muscles of gsg(-/-) mice exhibited in vivo Evans Blue dye permeability, while the principal extraocular muscles did not. Disruption of gamma-sarcoglycan produced secondary displacement of alpha- and beta-sarcoglycans in the extraocular muscles. The intensity of immunofluorescence for dystrophin and alpha- and beta-dystroglycan also appeared to be slightly reduced. Utrophin localization was unchanged. The finding that sarcoglycan disruption was insufficient to elicit alterations in extraocular muscle suggests that loss of mechanical stability and increased sarcolemmal permeability are not inevitable consequences of mutations that disrupt the dystrophin-glycoprotein complex organization and must be accounted for in models of muscular dystrophy.

Animals↗
PubMed2001

Rhinovirus infection induces expression of type 2 nitric oxide synthase in human respiratory epithelial cells in vitro and in vivo.

BACKGROUND: Human rhinovirus (HRV) infections are the predominant cause of the common cold and are associated with exacerbations of asthma. Nitric oxide (NO) may play an important role in host defense by means of its potent antiviral properties. OBJECTIVE: We sought to determine whether epithelial expression of type 2 nitric oxide synthase (NOS 2), which produces NO, is induced on rhinovirus infection in vitro and in vivo. METHODS: Primary cultures of human airway epithelial cells were infected with HRV-16, and NOS 2 mRNA expression was assessed by conventional and real-time RT-PCR and NOS 2 protein by using Western blot analysis. Human subjects were also infected with HRV-16 in vivo, and mRNA for NOS 2 was assessed in nasal epithelial scrapings obtained before and after infection. RESULTS: NOS 2 mRNA levels increased within 8 hours after HRV-16 infection of cultured cells and remained elevated up to 48 hours after infection. NOS 2 protein was elevated at 24 hours. Induction of NOS 2 did not occur with UV-inactivated HRV-16 but could be reproduced by using double-stranded RNA, indicating that induction was dependent on viral replication. Increased NOS 2 expression was also observed in nasal epithelial scrapings during symptomatic colds. CONCLUSION: Increased epithelial expression of NOS 2 mRNA occurs as part of the host response to HRV infection in vitro and in vivo. Given the antiviral effects of NO, we speculate that increased host production of NO may play an important role in host defense during HRV infections.

Bronchi↗
PubMed2001

Missed opportunities? Coercion or commitment: policies of prevention.

The DOTS strategy (directly observed therapy, short course) has been the cornerstone of international TB control policy since the early 1990s. This strategy has provided the international community with an advocacy tool to harness funds for TB as well as a method for helping country programs to achieve high cure rates for TB. But as much as the strategy is seen as successful by some, it is perceived as unsuccessful by others. This paper looks at the results of the introduction of DOTS into control programs and discusses research relating to direct observation of treatment. It asks how policies like DOTS are created, and how they are administered and transferred from the international to the national and finally to the local level. The discipline of public health policy is used to interrogate the creation and history of the DOTS strategy in order to find ways of aiding the transfer of the policy to national and local levels. Finally, the paper asks whether the concepts of "control" and "elimination" continue to be useful in the management of infectious diseases. We ask whether it is time to change the perspective to policies that focus more on the context of implementation and the importance of the development of care, integration, and flexibility rather than cure, targets, and short-term solutions.

Coercion↗
PubMed2001

Nitric oxide inhibits rhinovirus-induced granulocyte macrophage colony-stimulating factor production in bronchial epithelial cells.

Infection of asthmatics with human rhinovirus (HRV) enhances airway eosinophilia and airways hyperreactivity. The current studies were performed to further characterize HRV-induced generation by human bronchial epithelial cells of granulocyte macrophage colony-stimulating factor (GM-CSF), a cytokine that could contribute to airway eosinophilia by increasing the survival and activation of eosinophils, and to determine the effects of the antiviral agent nitric oxide (NO) on HRV-induced GM-CSF production. Maximal levels of messenger RNA (mRNA) for GM-CSF were seen 1 h after HRV infection. Expression was sustained through 24 h and declined by 48 h. GM-CSF protein was detected in cell supernatants by 2 h after infection and reached maximal concentrations by 24 h, with the most rapid rate of production occurring from 2 to 7 h. The NO donor 3-(2-hydroxy-2-nitroso-1-propyl-hydrazino)-1-propanamine (NONOate) inhibited HRV-induced GM-CSF protein production in a time- and dose-dependent fashion. NONOate also inhibited HRV-induced GM-CSF mRNA levels at both times (1 and 4 h) examined. NONOate increased GM-CSF mRNA stability, suggesting that reduced mRNA levels were due to inhibition of transcription. The transcription factor nuclear factor-kappa B was rapidly induced by HRV infection, but was not inhibited by NONOate, implying a role for other transcription factors. Thus, NO may play an important anti-inflammatory role in virally induced exacerbations of diseases such as asthma.

Animals↗
PubMed2001

Needing to know? Ethical dilemmas in leprosy treatment and control.

A young man presents to your local clinic in a leprosy endemic country with a small patch of discoloured skin on his right forearm. The diagnosis is clear. You start to explain, but the man stops you: he doesn't want to hear more, just requests the medicine. But you are 'in conflict', and not just by the desire to discuss the situation more fully with your patient before prescribing a drug. The local public health team, of which you are a part, is currently evaluating the impact on the community's health of a patient education programme which necessitates informing all new leprosy cases of their diagnosis. What should you do? And can bio-ethics help?

Ethics, Medical↗
PubMed2001

Under-diagnosis of smear-positive pulmonary tuberculosis in Nairobi, Kenya.

SETTING: Nairobi City Council Chest Clinic, Nairobi, Kenya. OBJECTIVE: To determine if under-reading of sputum smears is a contributing factor in the disproportionate increase in smear-negative tuberculosis in Nairobi, Kenya. METHODOLOGY: Between October 1997 and November 1998, patients fulfilling the local programme definition of smear-negative presumed pulmonary tuberculosis were enrolled in the study. Two further sputum specimens were collected for examination in a research laboratory by fluorescence microscopy. RESULTS: Of 163 adult subjects enrolled, 55% were seropositive for the human immunodeficiency virus type 1 (HIV-1). One hundred subjects had had two pre-study sputum smears assessed before recruitment and produced two further sputum specimens for re-examination in the research laboratory; of these 19 (19%) were sputum smear-positive on re-examination and a further seven (7%) became smear-positive on second re-examination. CONCLUSIONS: Of those patients with smear-negative presumed pulmonary tuberculosis by the local programme definition, 26% were smear-positive when reexamined carefully with two repeat sputum smears. This suggests that the high rates of smear-negative tuberculosis being seen may in part be due to under-reading. This is probably as a result of the overwhelming burden of tuberculosis leading to over rapid and inaccurate sputum examination. Retraining of existing technicians and training of more technicians is likely to reduce underreading and increase the yield of smear-positive tuberculosis. This finding also stresses the need for regular quality assurance.

AIDS-Related Opportunistic Infections↗
PubMed2001

Evidence for rectus extraocular muscle pulleys in rodents.

PURPOSE: Extraocular rectus muscle (EOM) pulleys are important determinants of orbital biomechanics in humans. In this study, the authors evaluated orbital connective tissue morphology, specifically characterizing rectus muscle pulleys, in the rat, a species with laterally placed eyes, afoveate vision, and a less complex visuomotor repertoire than primates. METHODS: Adult rat orbits were paraffin processed and serially sectioned for histochemical and immunohistochemical staining. Frozen sections of enucleated globes with intact EOMs and associated connective tissue were also studied with myosin immunohistochemistry and histochemistry for the mitochondrial enzyme, nicotinamide adenine dinucleotide (NADH)-tetrazolium reductase, to delineate the orbital layer relationship with the pulley tissue. RESULTS: Focal condensations of collagenous connective tissue were found in relationship to the rectus muscles in the equatorial Tenon's fascia, similar to those described as human recti muscle pulleys. The fibroelastic pulley rings were coupled to adjacent EOM pulleys by bands containing collagen and elastin. The coupling of pulleys to the orbital walls was significantly less than that previously described in humans. As in humans, there was a dual insertion of rodent rectus muscles, with the orbital layer inserting on the muscle pulley and the global layer attaching to the sclera. CONCLUSIONS: The data support the presence of structures in the rat orbit that are the morphologic equivalent of the human rectus pulley system. Although rodent and human pulleys were similar in many respects, there were species-specific properties that may relate to established differences in orbital anatomy and/or visuomotor behavior. These data extend the rectus muscle pulley concept to rodents and may provide insight into pulley structure-function relationships.

Animals↗
PubMed2000

Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya.

HIV infection has now been consistently identified as the major cause of death in young Africans in both urban and rural areas. In Africa, several studies have defined the clinical presentation of HIV disease but there have only been a limited number of autopsy studies. Because of the scarcity of autopsy data and the possibility of differing type and frequency of opportunistic infections between different geographic locations we set out to study consecutive new adult medical admissions to a tertiary referral hospital in Nairobi and perform autopsies on a sample of HIV-1-positive and HIV-1-negative patients who died in the hospital ward. Basic demographic data were collected on all patients admitted to two acute medical wards over an 11-month period. Final outcome and final clinical diagnoses were recorded at discharge or death. An autopsy examination was requested if the patient died in the ward. Autopsy examination was performed in 75 HIV-1-positive (40 men, 35 women) and 47 HIV-1-negative (28 men, 19 women) adults who died in the hospital. This represented 48.4% of all HIV-1-positive deaths and 33.3% of all HIV-1-negative deaths. Tuberculosis (TB) and bacterial and interstitial bronchopneumonia accounted for 96% of the major pathology in patients found to be HIV-1-positive at autopsy. TB was present in half the HIV-1-positive autopsy patients and was disseminated in over 80% of cases. Meningeal involvement was present in 26% of those with disseminated TB. By contrast, TB was much less common in the HIV-1-negative patients at autopsy in whom bacterial bronchopneumonia and malignancies were the most common pathologies. The type pathology found in the HIV-1-positive autopsy patients was not different than that found in other areas in Africa so far studied.

AIDS-Related Opportunistic Infections↗
PubMed2000

Zonal organization of flocculo-vestibular connections in rats.

Anatomical and electrophysiological evidence has contributed to the hypothesis that microzones in the mammalian flocculus are organized to reflect control of eye movements in the planes of semicircular canals. Adult male Long-Evans rats received iontophoretic injections of FluoroGold and/or tetramethylrhodamine dextran amine (10,000 molecular weight, "FluoroRuby") into the vestibular nuclei. The distribution of retrogradely labeled Purkinje cells revealed that efferent projections from the dorsal surface of the flocculus and the ventral paraflocculus to the superior vestibular nucleus, rostral medial vestibular nucleus, ventral lateral vestibular nucleus, and caudal aspect of the vestibular nuclear complex (caudal medial vestibular nucleus, inferior vestibular nucleus and nucleus prepositus hypoglossi) tended to correspond to previously identified climbing fiber zones [Ruigrok et al. (1992) J. comp. Neurol. 316, 129-150] in a manner consistent with other mammals. However, vestibular nucleus projections from the ventral surface of the flocculus did not appear to respect climbing fiber zonal boundaries. Rather, climbing fiber zones each contained interdigitated groups of Purkinje cells that project to different vestibular nuclear regions. It is suggested that this pattern of flocculus efferent organization is a specialization for controlling the activity of primary and accessory extraocular muscle pairs to confine vestibulo-ocular reflexes within semicircular canal planes when the "center of regard" is located at different eccentricities.

Animals↗
PubMed2000

Anti-tuberculosis treatment in private pharmacies, Kathmandu Valley, Nepal.

SETTING: Urban municipality of 150000 citizens in Kathmandu Valley, Nepal. OBJECTIVE: To determine 1) the perceptions among private pharmacists of characteristics of tuberculosis (TB) patients visiting private pharmacies in the area, 2) the sales of different anti-tuberculosis drugs, and 3) the interaction between private health providers and pharmacists. DESIGN: Between January and April 1998, semi-structured interviews were conducted with 98% (49/50) of the private drug-retailers in the area. RESULTS: Thirty-two (65%) pharmacies had sold anti-TB drugs during the last month. Forty-three (88%) said that most TB patients were of low socio-economic status and rarely bought drugs for more than a week at a time. Only eight (16%) reported that TB patients usually returned to buy the full course of drugs. Seventy-two per cent of total spending on anti-tuberculosis drugs was for different kinds of combinations of drugs. Nine per cent was spent on plain rifampicin, believed to be sold only to tuberculosis/leprosy patients. During the previous month, 5/13 (38%) of pharmacies with no doctors attached had sold anti-tuberculosis drugs compared with 27/38 (71%) of pharmacies with doctors attached to them (P < 0.05). CONCLUSION: The private sector offers an available and acceptable but non-affordable service for many TB patients. A substantial amount of anti-TB drugs are being sold in the private pharmacies. There is therefore a potential role for pharmacists to play in collaborative efforts between the private and public sector in TB control activities.

Adult↗
PubMed2000

Surveillance of drug-resistant tuberculosis and molecular evaluation of transmission of resistant strains in refugee and non-refugee populations in North-Eastern Kenya.

SETTING: Three refugee camp complex clinics and an adjacent non-refugee treatment centre in North-Eastern Kenya. OBJECTIVES: To use conventional and molecular epidemiology tools to determine: 1) the prevalence of drug resistance in newly diagnosed patients with smear-positive pulmonary tuberculosis in refugee and non-refugee populations; 2) risk factors for resistance in the two populations; and 3) whether IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping showed similarities in DNA fingerprinting patterns of drug-resistant isolates that could infer transmission within and between the two populations. RESULTS: Of 241 isolates from the camps, 44 (18.3%) were resistant to one or more drugs, seven of which (2.9%) were multidrug-resistant TB (MDR-TB). Of 88 isolates from the non-refugees, five (5.7%) were resistant to one or more drugs without MDR-TB. Drug resistance was higher in the camps than in the non-refugee population (OR = 3.7; 95%CI 1.42-9.68; P < 0.007). Resistance was significantly higher in one camp compared with the other two, despite a comparable ethnic distribution. Unusually, females were more associated with drug resistance than their male counterparts in both populations (OR = 2.3; 95%CI 1.2-4.8; P = 0.008). There was evidence of transmission of streptomycin-resistant strains in the refugee population. DNA fingerprints of resistant strains from the non-refugee population were unique and different from those in the refugee camps. CONCLUSION: The observed high levels of drug resistance and MDR-TB, combined with evidence of transmission of strains resistant to streptomycin in the refugee population, suggest a need for strengthened TB control programmes in settings with a high risk of developing drug-resistant strains.

Adolescent↗
PubMed1999

The development of extraocular muscle calcium homeostasis parallels visuomotor system maturation.

Extraocular muscle is modulated by unique genetic and epigenetic factors to produce an atypical phenotype. As a prelude to regulation studies, we characterized the development of cation homeostasis in the predominately fast-twitch extraocular muscles. By atomic absorption spectroscopy, total muscle calcium content declined from birth to postnatal day 27 and, thereafter, stabilized at a low level in limb but increased dramatically in extraocular muscle (to 40x limb values). By ELISA, the slow isoform of sarcoplasmic reticulum Ca2+-ATPase predominated in neonatal eye muscle, but subsequently was largely replaced by the fast isoform. This replacement in eye muscle was completed later than in limb. Residual, slow Ca2+-ATPase likely resides in an unusual slow tonic fiber type characteristic of eye muscle. Maturation of the definitive extraocular muscle Ca2+-ATPase pattern paralleled myofiber Ca2+ and sarcoplasmic reticulum content. These data show that, like myosin heavy chain expression patterns, the development of cation homeostatic mechanisms in extraocular muscle parallels landmarks in the maturation of vision and eye movement control systems. Findings suggest that cation homeostasis in extraocular muscle may be susceptible to perturbations of the developing visual sensory system, as we have previously shown for myosin.

Aging↗
PubMed1999

Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns.

The genetic and epigenetic influences that establish and maintain the unique phenotype of the extraocular muscles (EOMs) are poorly understood. The vestibulo-ocular reflex (VOR) represents an important input into the EOMs, as it stabilizes eye position relative to the environment and provides a platform for function of all other eye movement systems. A role for vestibular cues in shaping EOM maturation was assessed in these studies using the ototoxic nitrile compound 3',3'-iminodipropionitrile (IDPN) to eliminate the receptor hair cells that drive the vestibulo-ocular reflex. Intraperitoneal injections of IDPN were followed by a 2-week survival period, after which myosin heavy chain (MyHC) analysis of the EOMs was performed. When IDPN was administered to juvenile rats, the proportion of eye muscle fibers expressing developmental and fast myosins was increased, while EOM-specific MyHC mRNA levels were downregulated. By contrast, IDPN treatment in adult rats affected only the proportion of fibers expressing developmental MyHC isoforms, leaving the EOM-specific MyHC mRNA unaltered. These data provide evidence that the VOR modulates EOM-specific MyHC expression in development. The lack of significant changes in EOM-specific MyHC expression in adult EOM following IDPN administration suggests that there may be a critical period during development when alterations in vestibular activity have significant and permanent consequences for the eye muscles.

Animals↗