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Biomedical subjects

J M Smith

Publications and source records attributed to J M Smith.

At least 163 records · Page 9Linked to original sources
PubMed1995

Immune response of mice infected with Schistosoma mansoni is modulated by antifibrotic treatment.

Mice infected with Schistosoma mansoni treated with beta-aminopropionitrile (BAPN), an antifibrotic agent, and the antischistosomal drug praziquantel (PZQ) were resistant to challenge for up to 5 weeks post-treatment. The combined treatment resulted in profound changes to the liver granuloma cell matrix and the composition and function of the cellular infiltrate. Although granulocytes always predominated in the infiltrate, the proportion of the cells which were macrophages was higher in mice treated with BAPN alone (39.2%) than in infected mice which were untreated (15.2%) or treated with PZQ alone (12.4%), and much higher than in mice given the combined treatment (1.8%). Two products associated with macrophage activation and cytotoxicity [tumour necrosis factor-alpha (TNF-alpha) and nitric oxide] were only detected in mice harbouring a patent infection and there was a strong positive correlation between the concentrations of each. The relatively low TNF-alpha concentrations in BAPN-treated mice seemed to be associated with the relatively small granulomas observed in these mice. BAPN treatment also led to changes in the proliferative response of the treated mice's macrophages to mitogen and soluble schistosome-egg antigen and in spleen cellularity; these changes are probably associated with the resistance to challenge infection observed in mice given BAPN with PZQ. It is clear that BAPN treatment changes the dynamics of the delayed-type hypersensitivity response within the granuloma and that this impacts on other immunological sites. How this relates to the maintenance of post-treatment resistance to a challenge infection has still to be elucidated.

Aminopropionitrile↗
PubMed1995

Infection control in general practice: results of a questionnaire survey.

BACKGROUND: Infection control is an important aspect of quality of care. General practitioners (GPs) have a high throughput of patients, some attending because of a communicable disease, others for investigations or minor operations. This situation provides an opportunity for the spread of infections. This study looked at the development of practice policies on infection control and the need for further information and guidelines. METHODS: A postal questionnaire was sent to 117 practices in a single Family Health Services Authority. The questionnaire contained sections to be completed by a GP and a practice nurse in each surgery. RESULTS: A response rate of 74.5 per cent was obtained. Of the practices replying, 85 per cent did not have a written infection control policy. Sterilization of instruments was carried out in over 90 per cent of surgeries. Autoclaves were used in almost four-fifths of these practices; most did not have any written procedures covering their use. Few practices provided information on procedures for infected patients or staff. A third of practices did not have a needlestick policy, and sharps incidents were not recorded in 42 per cent of surgeries. Three-quarters of practices said that they would welcome guidelines on infection control. Half of the practice nurses thought that more training on infection control was required. CONCLUSIONS: The need for more training and the implications of the information from the study on the development and implementation of guidelines are discussed. Recommendations are made which aim to increase the awareness of this issue by means of guidelines and training focused on practice nurses.

Disinfection↗
PubMed1995

A technique for measurement of the extent of spatial organization of atrial activation during atrial fibrillation in the intact human heart.

Atrial fibrillation (AF) is a common clinical problem, associated with considerable morbidity and mortality, for which effective management strategies have yet to be devised. The absence of objective measures to guide selection of antiarrhythmic drug therapy for maintenance of sinus rhythm leaves only clinical endpoints (either beneficial or detrimental) for assessment of drug action, with occasional catastrophic consequences. As part of an attempt to provide an objective framework for the assessment of antiarrhythmic drug action on the electrophysiologic determinants of atrial fibrillation, we have developed a measure of the spatial organization of atrial activation processes during atrial fibrillation. By recording activation sequences at multiple equally spaced locations on the endocardial surface of the atria during atrial fibrillation in humans and determining the degree of correlation between these activation sequences as a function of distance, we have been able to construct spatial correlation functions for atrial activation. We have found that atrial activation remains well-correlated, independent of distance during normal sinus rhythm and atrial flutter. During atrial fibrillation, correlation decays monotonically with distance and the space-constant for this decay may be used to describe the relative spatial organization of atrial fibrillation. We provide examples of the impact of antiarrhythmic agents on the space-constant and suggest that assessment of the relative spatial organization of atrial activation using this methodology may potentially provide an objective framework to guide therapy in patients with AF.

Adenosine↗
PubMed1995

Nonpharmacologic approaches to the treatment of atrial fibrillation and atrial flutter.

The high prevalence of atrial fibrillation, the associated morbidity and mortality, the absence of safe and effective drug therapy, and an increased understanding of the pathophysiologic basis of atrial fibrillation and flutter have collectively led to the development of novel nonpharmacologic treatments for the management of these arrhythmias, including the CORRIDOR and MAZE surgical procedures, catheter-based ablation and modification of AV conduction, catheter-based ablation of atrial flutter and fibrillation, and internal atrial defibrillation. These surgical and catheter-based techniques offer potentially curative therapy while sparing the long-term risk of antiarrhythmic drug therapy. For patients with typical atrial flutter, catheter ablation affords to cure rate in excess of 70%. As technological innovations further facilitate identification and ablation of the critical isthmus in the floor of the right atrium, success rates should improve substantially. For patients with atrial fibrillation, AV junction ablation with implantation of a rate-responsive ventricular pacemaker should be considered palliative therapy, as should modification of AV junction conduction. The MAZE procedure offers very high cure rates, but because it currently involves open heart surgery, patient selection is critical. Catheter-based procedures emulating aspects of the MAZE procedure may one day offer cure rates comparable to those of the surgery itself, but additional research and technological development are necessary to further define and refine the minimal effective procedure, and then to facilitate the placement of contiguous, full-thickness lesions in precise three-dimensional configurations. In the interim, the implantable automatic atrial defibrillator may offer a means for rapidly restoring sinus rhythm without the risks of long-term antiarrhythmic drug therapy.

Atrial Fibrillation↗
PubMed1995

Low-energy internal cardioversion for atrial fibrillation resistant to external cardioversion.

UNLABELLED: Internal Cardioversion. INTRODUCTION: This report describes the electrical conversion of atrial fibrillation in two morbidly obese patients refractory to external cardioversion at 360 J. METHODS AND RESULTS: The two patients were lightly sedated and underwent placement of decapolar catheters in the coronary sinus and right atrial appendage. All ten electrodes of each decapolar catheter were electrically coupled, and defibrillation was attempted at successively increasing levels using a biphasic decaying exponential waveform generated by an external defibrillator. Both patients were returned to normal sinus rhythm using < or = 10 J without complication. CONCLUSION: Internal cardioversion is effective in restoration of sinus rhythm in some patients refractory to conventional forms of therapy.

Aged↗
PubMed1995

CheA, CheW, and CheY are required for chemotaxis to oxygen and sugars of the phosphotransferase system in Escherichia coli.

We carried out studies with Escherichia coli to determine the site at which the methylation-independent pathways for taxis to oxygen and to sugars of the phosphoenolpyruvate:sugar phosphotransferase transport system converge with the methylation-dependent chemotaxis pathways. Using genetic reconstitution of the pathways in a null strain, we determined that all pathways examined required the products of the genes cheA, cheW, and cheY. Thus, we conclude that both the methylation-independent and methylation-dependent pathways converge at CheA, the histidine kinase product of cheA.

Bacterial Proteins↗
PubMed1995

Electrophysiologic basis, surgical development, and clinical results of the maze procedure for atrial flutter and atrial fibrillation.

After more than a decade of experimental and clinical research into the basic mechanisms underlying atrial fibrillation, we were able to develop a surgical procedure that appears to cure the arrhythmia. This surgical procedure has been used in 100 patients in our institution and in a total of approximately 130 patients by surgeons in other institutions. The surgical results have been excellent, which indicates the sophisticated electrophysiologic mapping systems are unnecessary and that the results are not surgeon-specific.

Animals↗
PubMed1994

Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen.

We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered.

Animals↗
PubMed1994

Development and characterization of nontumorigenic and tumorigenic epithelial cell lines from rat dorsal-lateral prostate.

We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirements for optimal growth. Growth of NRP-154 cells is stimulated by dexamethasone and insulin, inhibited by transforming growth factor beta 1, but not significantly altered by epidermal growth factor, cholera toxin, dihydrotestosterone, retinoic acid, or 1 alpha,25-dihydroxyvitamin D3. Our data suggest that the NRP-152 and NRP-154 cell lines are suitable systems for analysis of normal prostate growth and prostatic carcinogenesis.

Acid Phosphatase↗
PubMed1994

1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat.

We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened tumor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24-5531 significantly enhanced the ability of tamoxifen to reduce total tumor burden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast cancer cell lines as well as primary cultures of cells from 2 patients with acute myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, "deltanoids," for the set of molecules composed of vitamin D and its synthetic analogues, in a manner similar to the naming of "retinoids" for the corresponding set of molecules related to vitamin A.

Adenocarcinoma↗
PubMed1994

Histogenesis of induced prostate and seminal vesicle carcinoma in Lobund-Wistar rats: a system for histological scoring and grading.

We have developed a grading system for the evaluation of the histogenesis of neoplastic lesions of the prostate and seminal vesicle of the laboratory rat. Prostatic and seminal vesicle carcinomas were induced in Lobund-Wistar rats by initiation with 30 mg/kg N-nitroso-N-methylurea i.v., followed by promotion with 40 mg testosterone propionate implants 1 week later and at 3-month intervals thereafter. Experimental and control groups were sacrificed at various time points between 5 and 11 months after dosing with N-nitroso-N-methylurea in order to visualize progressive stages of carcinogenesis of the dorsolateral prostate, the anterior prostate, and the seminal vesicle. A system of staging was created which allows three different categories (in situ change, invasion, desmoplasia) of tumor development to be ranked progressively in a manner conducive to nonparametric analysis. Each category was then further subdivided to create a total of six stages. This system can be used to evaluate agents which modify tumor induction or suppression. The application of this staging system to the measurement of the effects of the synthetic retinoid, 4-hydroxyphenyl retinamide, on prostatic carcinogenesis in the Lobund-Wistar rat is described.

Animals↗