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Biomedical subjects

B Fox

Publications and source records attributed to B Fox.

At least 37 records · Page 2Linked to original sources

Insecticide-treated cattle for tsetse control: the power and the problems.

Trypanosomiasis control increasingly involves financial input from livestock owners and their active participation. If control is carried out on smaller scales than in the past, methods such as aerial and ground spraying and sterile insect techniques will have reduced application. There will be increased reliance on trypanocidal drugs, and bait methods of tsetse control--where flies are attracted to point sources and killed. If drug resistance develops, cheap and simple bait methods offer the only means of disease control that might be applied, and paid for, by stockowners themselves. The methods have been effective in some circumstances, but not in others, and it is important to understand the reasons for the successes and the failures. Analysis is presented of the results of two Tanzanian tsetse control campaigns involving the use of insecticide-treated cattle. Between 1991 and 1996, following the introduction of widespread dipping in the Kagera Region, trypanosomiasis declined from >19000 cases to <2400 and deaths from >4000 to 29. On four ranches in the region, tsetse have been almost eliminated and trypanosomiasis prophylaxis is no longer used. Similarly aggressive use of pyrethroids on Mkwaja Ranch in Tanga Region has not had such dramatic effects. Tsetse and trypanosomiasis are still common, despite high levels of prophylaxis and the deployment of approximately 200 odour-baited targets. The difference in the results is attributed to a combination of the much smaller area covered by treated animals at Mkwaja, a greater susceptibility to re-invasion and a more suitable habitat for the flies. A better understanding of the dynamics of the use of insecticide-treated cattle is needed before we can predict confidently the outcome of particular control operations.

Animal Husbandry↗

The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila.

Wingless (Wg) is a member of the Wnt family of growth factors, secreted proteins that control proliferation and differentiation during development. Studies in Drosophila have shown that responses to Wg require cell-surface heparan sulphate, a glycosaminoglycan component of proteoglycans. These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wnt receptor complex. We demonstrate here that the protein encoded by the division abnormally delayed (dally) gene is a cell-surface, heparan-sulphate-modified proteoglycan. dally partial loss-of-function mutations compromise Wg-directed events, and disruption of dally function with RNA interference produces phenotypes comparable to those found with RNA interference of wg or frizzled (fz)/Dfz2. Ectopic expression of Dally potentiates Wg signalling without altering levels of Wg and can rescue a wg partial loss-of-function mutant. We also show that dally, a regulator of Decapentaplegic (Dpp) signalling during post-embryonic development, has tissue-specific effects on Wg and Dpp signalling. Dally can therefore differentially influence signalling mediated by two growth factors, and may form a regulatory component of both Wg and Dpp receptor complexes.

Animals↗

In vivo studies of gene expression via transient transgenesis using lipid-DNA delivery.

As the sequencing of the human genome proceeds, the need for a new screen for in vivo function is becoming apparent. Many investigators are turning to various transgenic models as a means of studying function. However, these approaches are very time consuming, with a transgene-expressing mouse model often taking months to establish. We have developed an efficient system for delivering genes in vivo, which allows the gene product to be studied as early as 24 h after introduction into the mouse model. The delivery system employs a novel cationic lipid, 1-[2-(9-(Z)-octadecenoyloxy)ethyl]-2-(8-(Z)-heptadecenyl)-3- (hydroxyethyl)imidazolinium chloride (DOTIM), and a neutral lipid, cholesterol, complexed with an expression vector containing the reporter gene chloramphenicol acetyl transferase (CAT). After a single intravenous injection of these complexes, several tissues were seen to express the transgene. High, persistent expression in the vascular endothelial cells in the mouse lung was obtained. Delivery of DNA in vivo has been evaluated by quantitative polymerase chain reaction and protein expression by CAT activity assays. In vivo studies showed reproducible expression in more than 500 mice injected via the tail vein. An early peak of expression was followed by lower, but sustained, expression for > 50 days. Transgene expression of CAT could also be identified by immunohistochemistry staining in mouse lung and appeared to be located within the capillaries. The pattern of in vivo expression could be modulated and targeted to specific organs by altering the lipid-DNA formulation. New expression vectors with altered introns and polyadenylation sites further improved expression. The expression reported here may be sufficient in magnitude, duration, and flexibility to be an attractive alternative, in some cases, to establishing transgenic animals by stable gene transfer.

Animals↗

Feasibility of a healthcare proxy counseling program for patients with Alzheimer's disease.

BACKGROUND: Although significant progress has been made in the implementation of advance directive counseling programs for cognitively intact patients, there is a paucity of information on the outcome of these programs with patients with Alzheimer's disease. This study investigated the prevalence of completed healthcare proxies in a sample of Alzheimer's disease outpatients, and the feasibility of a systematic proxy counseling program for this population. METHODS: The setting was a geriatric psychiatry clinic. Ninety-four patients with Alzheimer's disease were surveyed for their previous completion of a healthcare proxy. All patients with capacity and without a proxy were approached to complete the advance directive with a lay counselor. RESULTS: Thirty-two percent (n = 30) of patients had completed a proxy prior to the initiation of a counseling program. Of patients without proxies (n = 64), 89% had capacity to complete one. Seventy-nine percent subsequently completed a proxy through the counseling program. Hispanics were least likely to have had a proxy prior to initiation of the program, yet were very willing to complete the document. CONCLUSIONS: The majority of patients with Alzheimer's disease in an outpatient setting did not have healthcare proxies, yet had the capacity and motivation to complete this advance directive. With physician input regarding the presence of decisional capacity, a lay counselor successfully implemented the counseling process. These results support the initiation of similar counseling programs for Alzheimer's outpatients.

Journal Article↗

Numerical computation of differential-algebraic equations for nonlinear dynamics of multibody android systems in automobile crash simulation.

The principle of virtual work is used to derive the Euler-Lagrange equations of motion in order to describe the dynamics of multibody android systems. The constrained variational equations are in fact differential-algebraic equations of high index and are cast as ordinary differential equations through differentiation of the constraint equations. The integration routine LSODAR and the fourth-order Runge-Kutta method are used to compute the generalized coordinates, their time derivatives and the body forces of two android models. The graphs of the constraint forces reveal the whiplash effect on the neck and that the stiffness of both multibody systems is due to large magnitude impulsive forces experienced by many bodies simultaneously.

Accidents, Traffic↗

Long-term benefits for Mäori of an asthma self-management program in a Mäori community which takes a partnership approach.

BACKGROUND: In 1991, an intervention trial of the efficacy of an asthma self-management plan was carried out in partnership with a rural Mäori community. The program relied on Mäori community health workers and other health professionals working in partnership, was delivered through clinics in traditional Mäori community centres and Mäori processes were followed throughout. The plan was shown to be effective in reducing asthma morbidity. OBJECTIVE: To assess whether the long-term benefits of the program extent beyond reduced asthma morbidity and the extent to which any additional benefits may be related to the partnership approach employed by the program. METHOD: Forty-seven (68%) of the original program participants were surveyed in August 1997. Participants were questioned on the program's impact in areas such as cultural development, health service access and lifestyle. RESULTS: In addition to the improvements in asthma morbidity, the program was found to have four key benefits: cultural affirmation; improved access to other health services; a greater sense of control for participants; and positive impacts on the extended family. CONCLUSIONS: The program's benefits extended beyond reduced asthma morbidity and were not due simply to the introduction of the asthma self-management plan but also to the partnership approach employed by the program. IMPLICATIONS: The study provides support for providing public health services for indigenous communities that take a partnership approach, utilise community expertise and are delivered in a way that is consistent with each community's cultural processes.

Adult↗

Effects of scopolamine on delayed-matching-to-sample and paired associates tests of visual memory and learning in human subjects: comparison with diazepam and implications for dementia.

Two experiments examined dose-related effects of 200, 400 and 600 micrograms scopolamine (n = 24, s.c.) and 5 and 10 mg diazepam (n = 6, PO) on parallel tests of visual memory and learning taken from the CANTAB battery. Scopolamine significantly impaired accuracy of performance on a delayed matching to sample test of visual recognition memory in a dose- and delay-dependent manner, but had only marginal decremental effects on a test of visuospatial paired associates learning. Scopolamine significantly lengthened decision times in a visual search matching to sample task at the 400 and 600 micrograms doses, without significantly affecting accuracy. The drug also impaired performance on tests of spatial (on accuracy and response time measures) and pattern (on response time only) memory. Most of the deleterious effects on scopolamine were removed by covariance analyses with indices of subjective sedation, but the effects of delayed matching accuracy and latency remained. By contrast, diazepam significantly impaired paired associates learning but affected delayed matching to sample in a delay-independent manner. These results suggest that scopolamine can produce selective deficits in tests of short-term visual recognition memory which do not depend on overall impairments in arousal and which contrast with deficits in visual associative learning produced by diazepam. They have implications for the pharmacological modelling of dementia and memory disorders in man and for the neurochemical substrates of the short-term recognition memory and associative learning for visual stimuli.

Adult↗

Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC.

We compared the efficacy of gene transfer in vitro and in vivo using various formulations of DNA-lipid complexes based on the novel cationic lipid EDMPC (1,2-dimyristoylsn-glycero-3-ethylphosphocholine, chloride salt). In vitro studies analyzed delivery of marker genes to four established cell lines, including two of pulmonary origin. The in vivo analysis used intralobar delivery of marker genes and CFTR to mice and rats. We observed a lack of positive correlation between those DNA-EDMPC formulations that delivered DNA most efficiently in vitro and those that worked best in vivo. Intralobar DNA delivery to rodents mediated by EDMPC was efficient. The high level of gene delivery by DNA-EDMPC formulations demonstrates that efficient lipid-mediated gene transfer to the lung is possible.

Animals↗

Reactive arthritis with a severe lesion of the cervical spine.

Reactive arthritis, or Reiter's disease, characteristically affects the joints of the lower limbs in an asymmetrical pattern. Usually it does not affect the cervical spine, and atlantoaxial subluxations are the exception. This paper describes the case of an HLA-B27-positive female patient with a sexually acquired reactive arthritis where a non-reducible atlantoaxial subluxation was present. The patient was followed from age 27 to 41. By the age of 38, an anterior decompression of the cervico-medullary junction was performed by a transoral approach; in a second stage, the patient underwent an occipito-cervical posterior fusion. The pathological study revealed a non-specific and chronic inflammatory infiltrate.

Adult↗

Intraluminal water increases expression of plasmid DNA in rat lung.

Effective gene delivery to specific organs is a major goal for human gene therapy. The lung's structure allows instillation of agents into the airspaces, directly adjacent to the lung epithelium. We hypothesized that the airspace instillation of hypotonic solutions would increase the permeability of the lung epithelium and increase DNA uptake. This hypothesis was tested by instilling plasmid DNA (p4241) encoding the luciferase gene in isotonic and hypotonic solutions. The highest luciferase expression in the lung was achieved after the instillation of this plasmid DNA in distilled water. Aerosolization of water just before the instillation of the plasmid DNA also enhanced the expression level of luciferase in the lung. In addition, an intralobar instillation of the plasmid DNA in water significantly increased the luciferase expression, suggesting that the instillation of the plasmid over a smaller surface area increased expression. Levels of expression could be measured for 3 days. Water increases the permeability of lung epithelial cells transiently and/or enhances gene expression and can be used to achieve gene expression in the lung airspaces for short intervals without toxicity.

Animals↗

Computed tomography of the brain in acute carbon monoxide poisoning.

Of 107 patients admitted to the South Western Hyperbaric Medical Centre with acute carbon monoxide poisoning for hyperbaric oxygen therapy 19 had cerebral imaging performed: 17 patients had CT, one patient had MRI and CT and one patient MRI alone. The role of brain CT is established in determining the prognosis from acute carbon monoxide poisoning. Brain imaging was indicated because of unconsciousness on admission and failure or delayed improvement in neurological status after initiation of hyperbaric oxygen therapy. Of the 18 patients who underwent brain CT, seven were found to have the characteristic changes of bilateral low attenuation areas within the globus pallidus and six had low attenuation changes within cerebral white matter. In two patients there were both globus pallidus and cerebral white matter changes. Out of the total of the 19 patients who were studied, four patients died, 10 recovered fully and five had variable disabilities ranging from short term memory loss to more severe cognitive impairment and physical disability. The role of CT and the practicalities of hyperbaric oxygen therapy for acute carbon monoxide poisoning are discussed in the light of the experience from a regional dedicated medical diving centre.

Acute Disease↗

Direct gene transfer for the understanding and treatment of human disease.

Direct gene transfer has been used to develop molecular genetic interventions for acquired diseases in several animal models. Through the use of intravascular catheters or anatomically localized injection of DNA liposome complexes, specific tissues can be transduced with recombinant genes. Several promising applications of this method for the study of vascular biology have been demonstrated by direct gene transfer into arteries in vivo. Delivery, via catheter, of genes that modulate the thrombogenic or proliferative properties of vascular cells may someday provide therapy for stenotic lesions of atherosclerosis or following angioplasty. Cancer is another acquired disorder in which direct gene transfer may improve the efficacy of treatment. Introduction of class I MHC or cytokine genes with antitumor or immunostimulatory effects have demonstrated promise in animal models. Direct transfer of an allogeneic class I MHC gene into tumors in vivo induces a CD8+ CTL response against weak antigens on poorly immunogenic tumors. The efficacy of this antitumor response can be augmented to induce regression of actively growing established tumors. Additional strategies, such as intratumoral delivery of combinations of multiple cytokine and MHC genes, may serve to improve the antitumor response. A clinical gene therapy protocol is underway to analyze the safety and efficacy of DNA liposome-mediated gene transfer in humans. Development of improved gene delivery systems and introduction of recombinant genes into visceral tumors by intravascular catheter will extend the application of direct gene transfer to immunotherapy of malignancies. These clinical trials of direct gene transfer will help to develop new treatment strategies for human diseases.

Animals↗

Immunomodulation in patients receiving intravenous Bryostatin 1 in a phase I clinical study: comparison with effects of Bryostatin 1 on lymphocyte function in vitro.

Bryostatin 1 is a protein kinase C activator that inhibits growth of tumour cells and activates lymphocytes in vitro, properties that have encouraged its use in phase 1 clinical studies as an anticancer agent. We investigated interleukin-2(IL-2)-induced proliferation and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC) from cancer patients receiving Bryostatin intravenously. After Bryostatin administration both LAK generation and proliferation were enhanced when patients' PBMC were stimulated with IL-2 in vitro. However, when normal donors' PBMC were cultured in vitro in the presence Bryostatin and IL-2, LAK induction was inhibited while IL-2-driven proliferation was increased. These effects were also seen following only 2 h exposure to Bryostatin and could be elicited by conditioned medium from Bryostatin-pretreated cells. Neither IL-4 nor interferon gamma was detected in the conditioned medium. Bryostatin in vitro was found to increase expression of IL-2 receptors on CD4+, CD8+ and CD56+ cells and augment the proportion of CD8+ cells in conjunction with IL-2. We conclude that Bryostatin in combination with IL-2 in vitro enhances proliferation and IL-2 receptor expression on lymphocytes, favouring CD8+ cells while suppressing the generation of LAK activity. Intravenous administration of Bryostatin increases the potential of IL-2 to induce proliferation and LAK activity in lymphocytes which, taken together with its putative direct antitumour effect, makes Bryostatin an interesting candidate for clinical trials in combination with IL-2.

Adjuvants, Immunologic↗

Limb blood flow, cardiac output and quadriceps muscle bulk following spinal cord injury and the effect of training for the Odstock functional electrical stimulation standing system.

As part of the assessment of the Odstock functional electrical stimulation (FES) standing system for mid to low thoracic lesion spinal cord injured (SCI) subjects, cardiac output, high blood flow and quadriceps muscle thickness were measured before and following an electrical stimulation muscle retraining programme. The same parameters were also measured in a group of uninjured subjects and in SCI subjects. It was found that there was no difference in cardiac output between the groups. However thigh blood flow was found to be around 65% of normal values in the spinally injured group. This returned to normal values following the retraining programme. The quadriceps muscle wasted to approximately 50% of its original thickness in the first 3 weeks following spinal cord injury. The retraining programme increased the muscle thickness to near normal values.

Adult↗