Reconstruction nailing for subtrochanteric fractures in the Pagetic femur.
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Bone Nails↗
Biomedical subjects
M Jackson
Publications and source records attributed to M Jackson.
Neural network classification of infrared spectra of control and Alzheimer's diseased tissue.
Artificial neural network classification methods were applied to infrared spectra of histopathologically confirmed Alzheimer's diseased and control brain tissue. Principal component analysis was used as a preprocessing technique for some of these artificial neural networks while others were trained using the original spectra. The leave-one-out method was used for cross-validation and linear discriminant analysis was used as a performance benchmark. In the cases where principal components were used, the artificial neural networks consistently outperformed their linear discriminant counterparts; 100% versus 98% correct classifications, respectively, for the two class problem, and 90% versus 81% for a more complex five class problem. Using the original spectra, only one of the three selected artificial neural network architectures (a variation of the back-propagation algorithm using fuzzy encoding) produced results comparable to the best corresponding principal component cases: 98% and 85% correct classifications for the two and five class problems, respectively.
Alzheimer Disease↗
Continuous warm versus intermittent cold blood cardioplegia for coronary bypass surgery in patients with left ventricular dysfunction.
Between October 1991 and March 1994, 108 consecutive patients with moderate to severe left ventricular dysfunction underwent non-emergency isolated coronary artery surgery under the care of one surgeon (A.R.). They were prospectively randomised to receiving either intermittent cold (Group 1-50 patients) or continuous warm (Group 2-58 patients) blood cardioplegia for myocardial protection. There were no significant differences in clinical outcome between the two groups, as judged by operative mortality, rates of perioperative myocardial infarction, the serum CKMB isoenzyme level at 2 and 18 h after operation, need for circulatory support, postoperative neurological deficit, or duration of hospital stay. Group 2 patients required significantly more potassium (68 vs 29 mmol, P < 0.001) to maintain diastolic arrest and also had higher serum potassium levels after removal of the cross-clamp (P < 0.001). However, sinus rhythm returned spontaneously with greater frequency (91.2% vs 45.8%, P < 0.001) in Group 2 patients. In conclusion this report suggests that retrograde continuous warm blood cardioplegia provides comparable myocardial protection to that achieved with retrograde intermittent cold blood cardioplegia in patients with moderate to severe left ventricular dysfunction undergoing isolated coronary artery surgery.
Aged↗
The cortical neuritic pathology of Huntington's disease.
We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Dose of propofol required to insert the laryngeal mask airway in children.
We have assessed the ease of insertion of the Brain Laryngeal Mask Airway (LMA) after induction of anaesthesia with propofol in 60 healthy unpremedicated children aged between four and nine years. Patients were randomly allocated into three groups: group A = propofol 2.5 mg.kg-1; group B = propofol 3 mg.kg-1 and group C = propofol 3.5 mg.kg-1. Propofol was mixed with lignocaine 0.5 mg.kg-1. Insertion conditions were assessed subjectively as good, acceptable, unacceptable or impossible. Insertion of the LMA was possible in all patients. Good and acceptable conditions were obtained in 35%, 70% and 95% in groups A, B, and C respectively (P < 0.0001). There was no statistically significant inter group variation in systolic and diastolic arterial pressure or in heart rate for five min after induction. All measured cardiovascular changes were considered to be clinically insignificant in healthy children. We conclude it is safe and effective to insert a LMA immediately after induction of anaesthesia with propofol 3.5 mg.kg-1.
Child↗
Congenital testicular maldescent: significance of the complete hernial sac.
OBJECTIVE: To test the hypothesis that testicular maldescent is rarely congenital in the absence of a complete hernial sac. PATIENTS AND METHODS: The study comprised 110 boys undergoing orchidopexy. Operative findings (complete hernial sac versus no hernial sac) were compared with recorded testicular descent at birth. RESULTS: Among 70 testes recorded as maldescended neonatally there was no example without a complete hernial sac at orchidopexy. Among 60 recorded as descended neonatally, 43 had no sac at orchidopexy. CONCLUSIONS: The findings are consistent with the hypothesis, though not with the proposition, that the presence of a complete hernial sac at orchidopexy constitutes proof of congenital testicular maldescent.
Age Factors↗
Efficacy of D0870 compared with those of itraconazole and amphotericin B in two murine models of invasive aspergillosis.
D0870 is a novel azole antifungal compound. It was compared with conventional amphotericin B and itraconazole therapy in two murine models of invasive aspergillosis, one a systemic nonimmunocompromised mouse model and the other a temporarily neutropenic mouse respiratory model. D0870 was given orally and achieved measurable concentrations in serum approximately proportional to the daily dose with accumulation over time if it was given twice daily. Amphotericin B at 3.3 mg/kg of body weight was given intraperitoneally for four to six doses, and itraconazole was given orally in a cyclodextrin suspension at 5 to 50 mg/kg daily or twice daily (BID). The duration of therapy varied from 7 to 14 days. In the nonimmunocompromised mouse model, D0870 at 25 mg/kg BID was slightly inferior to amphotericin B and itraconazole with regard to mortality, with a median survival of 20 days for the three groups (P = 0.03 compared with amphotericin B). However, D0870 at 25 mg/kg BID was inferior to amphotericin B (but not itraconazole) with respect to renal culture (P = 0.01) and brain culture (P = 0.0001) results. Only amphotericin B was statistically superior to controls with regard to mortality. In the neutropenic mouse respiratory model, D0870 at 50 mg/kg/day was superior to amphotericin B, itraconazole, and controls with regard to mortality. D0870 at both 25 and 50 mg/kg/day was statistically superior to controls with regard to lung culture results (P = 0.004 to 0.04). A second experiment with a higher inoculum showed that no drug regimen was effective in that model. In all models low doses and concentrations of D0870 in serum were ineffective. D0870 has some efficacy for the treatment of invasive aspergillosis when it is given at modest doses.
Amphotericin B↗
The use and misuse of FTIR spectroscopy in the determination of protein structure.
Fourier transform infrared (FTIR) spectroscopy is an established tool for the structural characterization of proteins. However, many potential pitfalls exist for the unwary investigator. In this review we critically assess the application of FTIR spectroscopy to the determination of protein structure by (1) outlining the principles underlying protein secondary structure determination by FTIR spectroscopy, (2) highlighting the situations in which FTIR spectroscopy should be considered the technique of choice, (3) discussing the manner in which experiments should be conducted to derive as much physiologically relevant information as possible, and (4) outlining current methods for the determination of secondary structure from infrared spectra of proteins.
Protein Conformation↗
Simple aromatics identified with a NFAT-lacZ transcription assay for the detection of immunosuppressants.
Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.
Animals↗
Macquarimicins, microbial metabolites from Micromonospora. I. Discovery, taxonomy, fermentation and biological properties.
A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.
Animals↗
Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum. I. Identity of the producing organism, fermentation and biological activity.
The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B against Candida albicans and, like papulacandin, loses activity in the presence of serum.
Aminoglycosides↗
Immunohistochemical evaluation of the developing outflow tract in the rat: achieving aortic to mitral fibrous continuity.
OBJECTIVES: To study the development of aortic to mitral fibrous continuity in the normal rat heart. METHODS: The hearts and great vessels of normally developed rat embryos and fetuses aged between 13.25 and 19.75 days of gestation were studied in conjunction with those of newborns aged 2 and 7 days post-partum. Standard histological methods and monoclonal antibodies raised against alpha smooth muscle actin (clone 1A4) and ventricular beta myosin heavy chain were used to demonstrate the ventricular outlets, ventriculo-arterial junction, inner heart curve and aortic infundibulum from the early stages of aortopulmonary septation to attainment of their definitive morphology. RESULTS: The two antibodies demonstrated temporal specificity (actin specificity increased post-partum; myosin specificity maximal during fetal period) in the labelling of their intended structures which correlated with their known developmental profile. Full-thickness fibrous continuity between aortic and mitral valves was not complete until 1 week after birth. After ventricular septation was complete, and thereafter towards the end of fetal life and beyond, separation was maintained by a muscular structure histologically identical to the vestigial netro-aortic root branch of the conduction tissue, a structure known to be derived from the primitive ventricular myocardium within the environs of the inner heart curve. CONCLUSIONS: Ventricular septation (occurring relatively early) and the attainment of fibrous continuity (occurring relatively late in development) are two independent processes. Muscular tissue separating left-sided arterial and atrioventricular valves is not derived from the aortic infundibulum but from the inner heart curve. Persistence of this structure is a feature of normal rat heart development and needs to be recognised when working with rodent-based animal models of congenital heart disease aimed at studying the disruption of the development of the ventricular outflow tracts.
Actins↗
Developing medical expertise: medical practitioners and the suspected murders of new-born children.
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England↗
Common arterial trunk and pulmonary atresia: close developmental cousins? results from a teratogen induced animal model.
OBJECTIVES: To examine morphological similarities between "classically different" congenital heart lesion types induced in fetal rats by the cardiac teratogen N,N'-bis(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine). METHODS: A single 200 mg oral dose of bis-diamine was given to 50 pregnant rats on the 9th gestational day. Eleven controls were fed an inert vehicle. Experimental and control rats were sacrificed from 15.4 days to term and embryos delivered by caesarean section. Age-matched embryos were processed for histology and sectioned at 7 microns. Cardiac morphology was compared between normal and bis-diamine exposed groups. RESULTS: Hearts from control embryos were morphologically normal. Those from bis-diamine treated embryos exhibited common arterial trunk (32%), overriding aortic valve with valvar pulmonary stenosis (40%) or infundibular atresia (4%), or ventricular septal defect (24%). Development of the outlet septum was affected in all hearts and the arterial duct was absent in 72% of cases. Whilst most hearts demonstrated the anatomy expected for their lesion, some with a common arterial valve demonstrated a pulmonary blood supply similar to that in human cases of pulmonary atresia, where, in the absence of an arterial duct, an essential systemic to pulmonary conduit was provided by a "persistent fifth aortic arch artery". In one such case the proximal part of the aortopulmonary septum was identified above a common valve. The septum was deviated to the left and was not continuous throughout the length of the arterial trunk, causing atresia of the pulmonary component. Others had muscular infundibular atresia but with a pulmonary blood supply arising directly from the solitary trunk as seen in common arterial trunk "type III". CONCLUSIONS: Bis-diamine consistently affects development of those structures which partition the arterial segment of the developing heart at one or more levels, often coexistent with agenesis of the sixth aortic arch arteries. Whilst the aortopulmonary and outlet septums were absent in most cases of common arterial trunk, some morphological duality was shared by classically different lesion types in these rat hearts, which may suggest a common aetiology for common arterial trunk "type III" and aortic overriding with absence of the outlet septum and pulmonary atresia.
Abnormalities, Drug-Induced↗
High-affinity reactions between antigen-specific T-cell receptors and peptides associated with allogeneic and syngeneic major histocompatibility complex class I proteins.
We report here that the intrinsic affinities of the antigen-specific T-cell receptors (TCR) of two unrelated CD8+ T-cell clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than the values generally thought to prevail for TCR. The TCR of one clone (2C) binds an allogeneic class I MHC protein (Ld) in association with an alpha-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) with an intrinsic affinity (intrinsic equilibrium association constant) of 1-2 x 10(7) M-1. The TCR of the other clone (4G3) binds a syngeneic class I MHC protein (Kb) in association with an ovalbumin octapeptide (SIINFEKL, termed pOV8) with an intrinsic affinity of 1.5 x 10(6) M-1. A comparison of the two clones, combined with current views of T-cell repertoire selection in the thymus, leads us to propose that TCR affinities are generally likely to be higher for allogeneic MHC-peptide complexes than for syngeneic MHC-peptide complexes.
Amino Acid Sequence↗
Conformation and self-association of the peptide hormone substance P: Fourier-transform infrared spectroscopic study.
Fourier-transform i.r. (f.t.i.r.) spectroscopy has been applied to the study of the conformational properties of substance P in aqueous solution. Spectra were obtained in the presence of lipid membranes and Ca2+ to assess the role of these factors in induction of the active conformation of the peptide. In aqueous solution substance P was found to be predominantly unstructured at physiological p2H, where the lack of long-range order is probably related to charge repulsion along the peptide chain. However, substance P aggregated in aqueous solution at p2H > 10.0. Little or no induction of secondary structure was seen on addition of the peptide to negatively charged bilayers, suggesting that interaction with a membrane surface does not play an important role in the stabilization of the active conformation of the peptide. In fact, substance P was found to aggregate in the presence of charged lipids, which would tend to hinder rather than enhance interaction with the receptor. We propose a model for the aggregation of substance P at the bilayer surface, based on our studies of the effect of p2H and lipid/peptide ratio on spectra. Addition of Ca2+ had no effect upon the secondary structure of the peptide or on its interactions with membranes.
Amino Acid Sequence↗
Isolation and sequence analysis of a cDNA encoding an adenine nucleotide translocator from Plasmodium falciparum.
A cDNA clone encoding the polypeptide for Plasmodium falciparum adenine nucleotide translocator (ANT) was isolated by screening a cDNA library with a 150 base pair fragment of genomic DNA which had been enzymatically amplified using two oligonucleotide primers designed from conserved regions of ANT's from other sources. The deduced amino acid sequence of the P. falciparum cloned insert was highly homologous to ANT of other organisms. Features of the sequence are discussed with reference to the targeting and membrane insertion of ANT. The protein has a molecular mass of 35 kDa as predicted from the 303 amino acids encoded in the open reading frame.
Amino Acid Sequence↗