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Biomedical subjects

R McLaughlin

Publications and source records attributed to R McLaughlin.

At least 19 recordsLinked to original sources

Comparative prospective study of foreign body removal from external auditory canals of cadavers with right angle hook or cyanoacrylate glue.

OBJECTIVES: Foreign bodies of the external auditory canal are a relatively common problem in emergency departments. Repeated attempts at removal with standard instrumentation can lead to significant ear injury. Recent case reports of using cyanoacrylate impregnated cotton buds suggest this is less traumatic and well tolerated by patients. No studies on this method have been performed. The objectives of this study were to identify whether there were significant differences in success rate, duration and injury caused by extracting beads from the external auditory canals of adult cadaveric ears using two different methods. This is the first study in a planned series of anatomical and clinical studies relating to foreign body extraction from the external auditory canal. METHODS: In this study the success rate, time taken and injury rate were assessed for removal of impacted spherical foreign bodies in the external auditory canals of cadavers using both a blunt right angle hook and cotton buds impregnated with cyanoacrylate glue. This process was performed by a specialist registrar in otolaryngology and repeated by a specialist registrar in emergency medicine. RESULTS: It was shown that both methods had a statistically similar success rate (two tailed binomial test p=0.5) and no injury was identified for either method. In addition the median extraction time for a right angle hook was 6 seconds and 42 seconds for cyanoacrylate. It was also noted that failed extraction was associated with a poor view of the foreign body in the external canal. This was caused by hair, a large tragus or tortuous external canal. CONCLUSIONS: The authors feel that cyanoacrylate impregnated cotton buds are as effective at removing impacted foreign bodies as a right angle hook but the process takes longer. It is believed that patients could tolerate this longer time as the cyanoacrylate method is in theory less traumatic.

Adhesives↗

Preoperative treatment with recombinant human growth hormone prevents ischemia reperfusion-induced diaphragmatic dysfunction.

BACKGROUND: Respiratory complications continue to be a major cause of morbidity and mortality following major vascular surgery. The recent UK Small Aneurysm Trial cited preoperative respiratory function as the major predictor of outcome following elective aortic surgery. AIM: The aim of this study was to investigate the effect of aortic clamping and revascularization on diaphragmatic muscle function in a small animal model and to evaluate the role of preoperative treatment with recombinant human growth hormone (rhGH) in preventing diaphragmatic muscle dysfunction. METHODS: Male Sprague-Dawley rats (n = 18) were randomized into one of three groups: control (n = 6) underwent laparotomy only; IR (n = 6) had a laparotomy with infrarenal cross-clamping for 30 min followed by lower torso revascularization for 2 h; IR + rhGH (n = 6) were treated with rhGH (Genotropin 0.3 IU/kg/day) for 5 days before laparotomy and aortic cross-clamping for 30 min followed by lower torso revascularization for 2 h. Diaphragmatic muscle contractile function was assessed ex vivo using electrical field stimulation in a tissue bath. RESULTS: Two hours of IR injury resulted in a significant impairment in diaphragmatic twitch (Control, 242.01 + 38.45 g; IR, 108.55 + 7.15 g). This impairment was prevented by pretreatment with rhGH (rhGH, 319.14 + 30.71 g; P < 0.01). Tetanic function was also significantly impaired by ischemia reperfusion injury (control, 605 + 77.63 g; IR, 228.12 + 14.38 g). Again, pretreatment with rhGH prevented this deterioration (IR + rhGH, 704.39 + 45.69 g; P < 0.05) compared with controls. CONCLUSION: The results of this study suggest that preoperative administration of rhGH may have a role in preventing the diaphragmatic dysfunction associated with infrarenal aortic cross-clamping and revascularization.

Animals↗

Complete genome sequence of an M1 strain of Streptococcus pyogenes.

The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.

Bacteriophages↗

The prognostic significance of CD44s and CD44v6 expression in stage two breast carcinoma: an immunohistochemical study.

AIMS: Expression of the v6 variant isoform of CD44 has been causally associated with the development of metastases. This study, using immunohistochemical techniques, examined the prognostic significance of CD44s and CD44v6 expression. METHODS: A cohort of 109 women presenting with stage 2 breast cancer, with a minimum follow-up of 5 years, were assessed. RESULTS: Eighty percent of patients demonstrated CD44v6 expression on immunohistochemical studies. CD44v6 expression in tissue sections was found to be independent of age, tumour size, grade, and lymph-node status. No significant association was demonstrated between CD44v6 expression and either disease-free or overall survival. Similar findings were observed for CD44s. CONCLUSIONS: CD44s and CD44v6 do not appear to be useful as prognostic indicators in early breast cancer. The increased expression of variant CD44 isoforms seen in breast neoplasia may merely be a marker for loss of control of alternative splicing within tumour tissue.

Adenocarcinoma↗

Melanotic neuroectodermal tumor of infancy (MNTI) of the hard palate: presentation and management.

OBJECTIVE: To discuss the presentation and management of melanotic neuroectodermal tumor of infancy (MNTI) of the hard palate. METHOD: Case presentation and literature review. CASE: A 6-month-old girl presented with a slow growing, non-tender anterior oral hard palate mass. Radiologic imaging revealed a well-circumscribed cystic lesion containing teeth. After excision, histopathologic and electron microscopic evaluation revealed MNTI. No recurrence was seen at 12-month follow-up. CONCLUSIONS: This case and a review of the literature reveal MNTI to be a rare, benign hard palate tumor, which may present as a smooth, firm, painless, slow-growing anterior palatal lesion. Imaging reveals a well-circumscribed cystic lesion. Complete excision should be curative. Management requires attention to the potential need for palatal reconstruction, orthodontic care and correction of secondary nasal deformities.

Female↗

Characterization of chimeric lipopolysaccharides from Escherichia coli strain JM109 transformed with lipooligosaccharide synthesis genes (lsg) from Haemophilus influenzae.

Previously, we reported the expression of chimeric lipopolysaccharides (LPS) in Escherichia coli strain JM109 (a K-12 strain) transformed with plasmids containing Haemophilus influenzae lipooligosaccharide synthesis genes (lsg) (Abu Kwaik, Y., McLaughlin, R. E., Apicella, M. A., and Spinola, S. M. (1991) Mol. Microbiol. 5, 2475-2480). In this current study, we have analyzed the O-deacylated LPS and free oligosaccharides from three transformants (designated pGEMLOS-4, pGEMLOS-5, and pGEMLOS-7) by matrix-assisted laser desorption ionization, electrospray ionization, and tandem mass spectrometry techniques, along with composition and linkage analyses. These data show that the chimeric LPS consist of the complete E. coli LPS core structure glycosylated on the 7-position of the non-reducing terminal branch heptose with oligosaccharides from H. influenzae. In pGEMLOS-7, the disaccharide Gal1--> 3GlcNAc1--> is added, and in pGEMLOS-5, the structure is extended to Gal1-->4GlcNAc1-->3Gal1-->3GlcNAc1-->. PGEMLOS-5 LPS reacts positively with monoclonal antibody 3F11, an antibody that recognizes the terminal disaccharide of lacto-N-neotetraose. In pGEMLOS-4 LPS, the 3F11 epitope is apparently blocked by glycosylation on the 6-position of the terminal Gal with either Gal or GlcNAc. The biosynthesis of these chimeric LPS was found to be dependent on a functional wecA (formerly rfe) gene in E. coli. By using this carbohydrate expression system, we have been able to examine the functions of the lsg genes independent of the effects of other endogenous Haemophilus genes and expressed proteins.

Acylation↗

Management of chronic osteoarthritic pain.

Osteoarthritis is a common cause of chronic pain in small animals. Although there is currently no known cure, the disease can often be palliated by a combination of weight control, regulated exercise, anti-inflammatory medications, and disease-modifying osteoarthritic agents. The diagnosis, recommended treatments, and many of the newer drugs and disease-modifying agents are discussed in this article.

Analgesics↗

Taxonomy and virulence of oral spirochetes.

All oral spirochetes are classified in the genus Treponema. This genus is in the family Spirochaetaceae as in Bergey's manual of systematic bacteriology. Other generic members of the family include Spirochaeta, Cristispira and Borrelia. This conventional classification is in accord with phylogenetic analysis of the spirochetes based on 16S rRNA cataloguing. The oral spirochetes fall naturally within the grouping of Treponema. Only four species of Treponema have been cultivated and maintained reliably: Treponema denticola, Treponema pectinovorum, Treponema socranskii and Treponema vincentii. These species have valid names according to the rules of nomenclature except for Treponema vincentii, which only has had effective publication. The virulence factors of the oral spirochetes updated in this mini-review have been discussed within the following broad confines: adherence, cytotoxic effects, iron sequestration and locomotion. T. denticola has been shown to attach to human gingival fibroblasts, basement membrane proteins, as well as other substrates by specific attachment mechanisms. The binding of the spirochete to human gingival fibroblasts resulted in cytotoxicity and cell death due to enzymes and other proteins. Binding of the spirochete to erythrocytes was accompanied by agglutination and lysis. Hemolysis releases hemin, which is sequestered by an outer membrane sheath receptor protein of the spirochete. The ability to locomote through viscous environments enables spirochetes to migrate within gingival crevicular fluid and to penetrate sulcular epithelial linings and gingival connective tissue. The virulence factors of the oral spirochetes proven in vitro underscore the important role they play in the periodontal disease process. This role has been evaluated in vivo by use of a murine model.

Animals↗

Diaphragmatic dysfunction secondary to experimental lower torso ischaemia-reperfusion injury is attenuated by thermal preconditioning.

BACKGROUND: Preconditioning describes the process whereby tissue exposure to a subcritical stress confers protection from subsequent injuries. This study assessed diaphragmatic muscle function after lower torso ischaemia-reperfusion (IR) and the role of thermal preconditioning in attenuation of this injury. METHODS: Sprague-Dawley rats were randomized into three groups (24 per group): a control group, an IR group that had aortic cross-clamping for 1 h followed by reperfusion, and a third group that received thermal preconditioning 18 h before IR. Diaphragmatic function was assessed at 24 h, 48 h and 7 days. RESULTS: IR resulted in significant diaphragmatic twitch and tetanic dysfunction compared with control muscle. Thermal preconditioning significantly attenuated this injury (P < 0.05). Mean(s.e.m.) muscle twitch and tetanic forces in the IR group were 204.9(17.2) and 282.7(19.2) g respectively at 24 h. Corresponding twitch and tetanic forces in preconditioned muscle were 270.4(25.1) and 552.0(35.2) g. CONCLUSION: This study demonstrated that systemic IR injury produced a respiratory muscle mechanical dysfunction that was attenuated by thermal preconditioning, at 24 h, 48 h and 7 days. Preconditioning may have a role in clinical practice, particularly before elective surgery.

Animals↗

Taurine protects against early and late skeletal muscle dysfunction secondary to ischaemia reperfusion injury.

OBJECTIVE: To assess the efficacy of the cytoprotective B-amino acid taurine in prevention of skeletal muscle dysfunction secondary to ischaemia-reperfusion (IR) injury. DESIGN: Randomised controlled animal study. SETTING: Biomedical research laboratory, teaching hospital, Republic of Ireland. ANIMALS: 96 Sprague Dawley rats. INTERVENTIONS: Rats were randomised into three groups (n = 24/group): control (sham); ischaemia-reperfusion (untreated); and ischaemia-reperfusion + taurine. A further 24 rats were given taurine alone. The rat cremaster skeletal muscle model of four hours of ischaemia followed by reperfusion was used. Taurine 4%wt/vol was given in the animals' water throughout the experiment, beginning 48 hours before the ischaemia was initiated. OUTCOME MEASURES: 8 rats were killed from each group and muscle contractile function was assessed using electrical field stimulation in a tissue bath at 24 hrs, 48 hrs and 7 days. RESULTS: Ischaemia followed by 24 hours, 48 hours or 7 days of reperfusion resulted in significant reduction in both muscle twitch and tetanic contractile function (p < 0.05). This was reversed by taurine, which resulted in significant preservation of twitch and tetanic contractility at all time points including one week of reperfusion (p < 0.05). There was no difference in muscle function between muscle treated with taurine after ischaemia-reperfusion and control muscle, with the same operation but without ischaemia, from 48 hours onwards. CONCLUSIONS: These data show that pharmaceutical use of the endogenous amino acid taurine, unlike many-other agents, protects electrophysiological function in skeletal muscle against both early and late ischaemia-reperfusion injury.

Animals↗

Alzheimer's disease may not be a spirochetosis.

It has been reported previously that spirochetes could be one of the causes of Alzheimer's disease (AD). In this study, we have attempted to reproduce these findings by examining fresh blood samples from 22 patients diagnosed with early stage (n = 16) and late stage (n = 6) AD. The patients were participants in a clinical drug trial. Fresh necropsy brain cortical specimens from AD patients (n = 7) were also examined. Spirochetes were observed microscopically in the blood of only one late-stage AD patient. None of the brain tissues showed the presence of spirochetes. Our results suggest that spirochetes are probably not associated with AD.

Aged↗

Factors affecting the formation of spherical bodies in the spirochete Treponema denticola.

The oral spirochete Treponema denticola typically is a helically shaped, motile bacterial cell. However, morphological variations of T. denticola cells in the form of "spherical bodies" are sometimes seen. Little is known about the environmental factors that cause their formation. The effects of oxygen, growth temperature, nutrient depletion and the addition of metabolic end-products were tested to determine their role in the morphogenesis of the spherical bodies. It was found that the age of the culture, the omission of individual components (yeast extract, rabbit serum, volatile fatty acids or thiamine pyrophosphate) from the medium and the addition of the metabolic end product lactic acid enhanced the formation of these bodies. However, their formation was decreased upon omission of the medium components asparagine and sodium bicarbonate.

Adaptation, Physiological↗

Recombinant human manganese superoxide dismutase attenuates early but not delayed skeletal muscle dysfunction following reperfusion injury.

OBJECTIVES: to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in prevention of early and late skeletal muscle ischaemia-reperfusion injury mediated by superoxide (O2-). Design : randomised controlled trial. MATERIALS: seventy-two Sprague-Dawley rats (250-350 g) randomised to receive either 7.5 mg/kg of rhMnSOD or saline. Four hours of ischaemia was induced in the cremaster muscle by dissecting free and clamping its vascular supply. Cremaster muscle contractile function was assessed following 90 minutes, 24, 48 hours and one week of reperfusion. Electrophysiological muscle function was assessed using electrical field stimulation in an organ bath system. RESULTS: muscle function in the untreated groups following ischaemia reperfusion was significantly reduced at 90 minutes, 24, 48 hours and one week of reperfusion (p <0.05). rhMnSOD significantly protected and maintained normal muscle function at 24 and 48 hours (p <0.001). However at one week of reperfusion there was a reduction in function of the treated muscle, such that there was no significant difference between treated and untreated muscle at this point in time. CONCLUSIONS: these data demonstrate that skeletal muscle dysfunction after ischaemia reperfusion injury is attenuated at 24 and 48 hrs of reperfusion by the superoxide scavenger rhMnSOD. This protective effect is not maintained after seven days of reperfusion.

Animals↗

6-Hydroxydopamine induced cardiac malformations and alterations of the autonomic nervous system in the developing chicken embryo.

6-Hydroxydopamine (6-OHDA) was injected into the air sac of developing chicken embryos on day E3 in order to study its effects on cardiac development both morphologically and biochemically. A dose-dependent teratogenic effect and fetotoxicity were observed in the 6-OHDA-treated embryos. Cardiac malformations, including ventricular septal lesions, detachment of the apical portions of the ventricles, cardiac hypertrophy, areas of coagulative necrosis with pyknotic nuclei and broken nuclear membranes, and swollen mitochondria were evident from gross histologic and ultrastructural examinations. A LD50 of 0.3 mg/egg on day E11 was obtained. Biochemically, 6-OHDA induced a significant dose-dependent reduction in the total cardiac choline acetyltransferase (ChAT) activities on days E8 and E11, followed by a recovery on days E15 and E20. The effects on muscarinic acetylcholine receptors (mAChRs) were less marked than on ChAT, indicating the effects on the cholinergic nervous system development are primarily presynaptic. There was a significant decrease in the level of norepinephrine (NE) and a delay in the appearance of detectable cardiac NE. It is suggested that 6-OHDA-induced cardiac malformation can be a useful model to study the mechanisms of cardiovascular development.

Adrenergic Agents↗