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Biomedical subjects

A C Cooper

Publications and source records attributed to A C Cooper.

At least 19 recordsLinked to original sources
PubMed2005

Hyporesponsiveness to erythropoietic therapy due to chronic inflammation.

The anaemia associated with chronic renal failure is multi-factorial. Although a relative erythropoietin deficiency is a major factor, it has also been recognized in recent times that uraemia is a chronic inflammatory state, and thus patients with renal failure also develop anaemia due to mechanisms associated with chronic inflammation. Thus, patients with chronic renal failure have activation of various immune cells, both monocytes and T-cells. These mononuclear cells have also been shown to release pro-inflammatory cytokines such as IL-1, IL-6, TNF-alfa and interferon gamma. These cytokines, particularly TNF-alfa and interferon gamma, are known to cause significant suppression of erythropoiesis. The exact molecular mechanism for this effect is not yet clear, but interferon gamma is an important stimulator of apoptosis in various cell types, including erythroid progenitor cells. This effect may be potentiated by other cytokines such as TNF-alfa, and this might then antagonise the anti-apoptotic action of erythropoietin on erythroid progenitors cells, thus reducing responsiveness to exogenous erythropoietic therapy. Chronic renal failure is also associated with increased hepcidin production which may also exacerbate the anaemia by inducing a functional iron deficiency in such patients.

Anemia↗
PubMed2002

Influence of carbon curvature on molecular adsorptions in carbon-based materials: a force field approach.

A general force field methodology is developed for description of molecular interactions in carbon-based materials. The method makes use of existing parameters of potential functions developed for sp(2) and sp(3) carbons and allows accurate representation of molecular forces in curved carbon environment. The potential parameters are explicitly curvature and site dependent. The proposed force field approach was used in molecular dynamics (MD) simulations for hydrogen adsorption in single-walled carbon nanotubes (SWNTs). The results reveal significant nanotube deformations and the calculated energies of adsorption are comparable to the reported experimental heat of adsorption for H2 in SWNTs.

Journal Article↗
PubMed2002

Acute administration of haloperidol induces apoptosis of neurones in the striatum and substantia nigra in the rat.

Chronic administration of typical neuroleptics is associated with tardive dyskinesia in some patients. This dyskinetic syndrome has been associated with loss of GABAergic markers in the basal ganglia but the cause of these GABAergic depletions remains uncertain. Haloperidol, a commonly prescribed typical neuroleptic, is known to be toxic in vitro, possibly as a consequence of its conversion to pyridinium-based metabolites and potentially by raising glutamate-mediated transmission. We report here that the in vivo, acute administration of a large dose of haloperidol resulted in a microglial response indicative of neuronal damage. This was accompanied by an increase in the number of apoptotic cells in the striatum (especially in the dorsomedial caudate putamen) and in the substantia nigra pars reticulata. These apoptotic cells were characterised by the stereotaxic injection of a retrograde neuroanatomical tracer into the projection targets of the striatum and substantia nigra pars reticulata prior to the systemic injection of haloperidol. This procedure confirmed that the dying cells were neurones and demonstrated that within the striatum the majority were striatopallidal neurones though relatively high levels of apoptotic striatoentopeduncular neurones were also seen.The possibility that chronic administration of haloperidol could induce cumulative neuronal loss in the substantia nigra pars reticulata and thereby induce the pathological changes which lead to tardive dyskinesia is discussed.

Animals↗
PubMed2001

Neuropsychological evidence for case-specific reading: multi-letter units in visual word recognition.

We describe a patient (GK) who shows symptoms associated with Balint's syndrome and attentional dyslexia. GK was able to read words, but not nonwords. He also made many misidentification and mislocation errors when reporting letters in words, suggesting that his word-naming ability did not depend upon preserved position-coded, letter identification. We show that GK was able to read lower-case words better than upper-case words, but upper-case abbreviations better than lower-case abbreviations. Spacing the letters in abbreviations disrupted identification, as did mixing the case of letters within words. These data cannot be explained in terms of letter-based reading or preserved holistic word recognition. We propose that GK was sensitive to the visual familiarity of adjacent letter forms.

Adult↗
PubMed2000

Task-specific effects of orientation information: neuropsychological evidence.

The deficits underlying orientation agnosia in a patient (MB) with a right fronto-temporo-parietal lesion were examined. Like similar patients in the literature, MB was impaired at discriminating whether objects were upright or not and, in copying, she tended to re-represent stimuli as upright. In addition, MB failed to show the normal effects of rotation on object identification; her naming of objects rotated 45 degrees from upright was no slower than her naming of upright items. Effects of the degree of rotation did emerge, however, when she had to perform a matching task that required mental rotation. The evidence suggests that orientation may be coded in several ways (e.g. separately between objects and relative to the viewer), and that brain-damage can selectively affect the use of some but not all types of orientation information.

Agnosia↗
PubMed2000

Coding space within but not between objects: evidence from Balint's syndrome.

The ability to make spatial judgements was examined in a patient demonstrating poor perception of multiple objects following bilateral parietal lesions, under conditions in which the presence of the stimuli to which judgements were made could be detected. The tasks required judgements of spatial length or the position of coloured parts of stimuli. We manipulated the degree to which two uprights in a display could be encoded into a single perceptual object using either stored knowledge or bottom-up cues based on 2D or 3D image relations. Performance was dependent on the presence of both bottom-up grouping and familiarity. However, connectedness in the image was not sufficient to benefit performance, when stimuli were separate objects in 3D space. This deficit in spatial judgements, arising following detection of the relevant stimulus elements, is attributed to an impairment in coding the spatial relations between separate perceptual objects. This deficit could be overcome if stimuli could be grouped in 3D, using bottom-up cues and top-down knowledge.

Agnosia↗
PubMed1999

Bone remodeling and structure in postmenopausal women treated with long-term, high-dose estrogen therapy.

Conventional hormone replacement therapy preserves bone mass predominantly by reducing bone turnover but does not exert significant anabolic skeletal effects. In contrast, high doses of estrogen have been shown to increase bone formation in animals and we have recently reported high bone mineral density values in women treated long-term with estradiol implant therapy. The aim of this study was to investigate the mechanisms by which high doses of estrogen may increase bone mass in postmenopausal women. Iliac crest biopsies were obtained from 12 women who had received long-term treatment with estradiol implants (at least 14 years), on demand, following hysterectomy and bilateral salpingo-oophorectomy. Indices of bone turnover, remodeling balance and cancellous bone structure were assessed by image analysis and compared with those of premenopausal women. Mean wall width was significantly higher in women treated with estradiol therapy than in premenopausal women (44. 8 +/- 4.8 vs 38.8 +/- 2.8 mm; mean +/- SD; p = 0.001) and eroded cavity area was significantly lower in the implant-treated women (3612 +/- 956 vs 5418 +/- 1404 mm(2); p = 0.001). Bone formation rate at tissue level and activation frequency were lower in the women treated with implants, although the differences were not statistically significant. Indices of cancellous bone structure were generally similar between the two groups. These results provide the first direct evidence that high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women and indicate that these are achieved by stimulation of osteoblastic activity.

Aged↗
PubMed1995

Rapid degradation of endothelin-1 by an enzyme released by the rat isolated perfused mesentery.

1. In vivo the effects of endothelin-1 (ET-1) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24.11, deamidase or carboxypeptidase A. Here, using as a model the isolated perfused mesenteric arterial bed of the rat, we have examined the involvements of these enzymatic activities in the vascular responses to ET-1. 2. Samples of Krebs buffer which had been recirculated through the mesenteric arterial bed for 30 min rapidly destroyed the activity of ET-1 as assessed either by bioassay on rings of rat thoracic aorta or by high performance liquid chromatography (h.p.l.c.). For instance, after 15 min incubation with the recirculated-Krebs solution (recirc-K) the contraction induced by 3 x 10(-9) M ET-1 was reduced by more than 90%. Contractions induced by sarafotoxin 6b (3 x 10(-9) M) were similarly suppressed by preincubation with recirc-K whereas those to Arg-vasopressin (3 x 10(-9) M) were unaffected. 3. The degradation of ET-1 by recirc-K was prevented by 1,10-phenanthroline (10(-3) M), abolished by heating the recirc-K solution to 90 degrees C for 15 min, and reduced by EGTA (5 x 10(-3) M) or ET-1(16-21) (10(-5) M). For instance, in the presence of ET-1(16-21) (n = 6) the contraction induced by ET-1 was reduced by only 40% after 15 min incubation with recirc-K buffer. Leupeptin (3 x 10-4 M), dichloroisocoumarin(5 x 10-5 M), phenylmethyl-sulphonyl fluoride (10-3 M), a combination of bacitracin (300 mg ml-1),bestatin (10-5 M), captopril (10-5 M), phosphoramidon (10-4 M) and thiorphan (10-4 M) or Polypep (aproprietary protein digest) did not inhibit the degradation of ET-1 by recirc-K.4. In experiments examining directly the vascular responses of the isolated perfused mesentery of the rat, the addition of cumulative concentrations of ET-1 to the recirculating Krebs solution caused small concentration-dependent increases in perfusion pressure. The inclusion of ET-1(16-2l), ET-1(17-21), or ET-1(18-21) (10-5M) greatly potentiated these responses, but not those to Arg-vasopressin or methoxamine.The effects of 1,10-phenanthroline or EGTA could not be examined in this system because these agents both depressed non-specifically the vasoconstrictor responses of the mesenteric vascular bed.5. Thus, the rat mesentery releases an enzyme that very rapidly destroys ET-1 or the very closely related peptide, sarafotoxin 6b but not Arg-vasopressin. This enzyme is most probably a metallopeptidase because of its sensitivity to inhibition by 1,10-phenanthroline or EGTA. It is particularly interesting that a simple vascular bed such as the mesentery produces such a powerful endothelin metabolising enzyme. It is tempting, therefore, to speculate that the endothelin degrading enzyme active at neutral pH that- we have found is important in the metabolism of ET-1 throughout the vasculature.

Animals↗
PubMed1993

In vitro activity of danofloxacin, tylosin and oxytetracycline against mycoplasmas of veterinary importance.

The activities of danofloxacin, a novel fluoroquinolone, and two other antimicrobials were determined in vitro against field isolates of seven Mycoplasma species of veterinary importance isolated from cattle, swine and poultry in five European countries. The minimum inhibitory concentrations (MIC) of danofloxacin, tylosin and oxytetracycline were determined against a total of 68 isolates. Danofloxacin showed excellent activity against isolates of all Mycoplasma species (range 0.008 to 0.5 microgram ml-1), but in some isolates there was evidence of reduced sensitivity to tylosin (range 0.008 to 2.0 micrograms ml-1) and oxytetracycline (range 0.008 to over 16.0 micrograms ml-1). Danofloxacin was more active than other antimicrobials against M hyopneumoniae, M dispar and M bovigenitalium, and showed activity similar to that of tylosin against M bovis and M gallisepticum. Tylosin was the most active against M synoviae and M hyosynoviae. Generally, oxytetracycline showed the poorest activity, but was superior to tylosin against M bovigenitalium. A second (final) MIC reading was taken for all isolates 14 or 21 days after the initial reading, and MIC values rose during that time. However, the increase seen in danofloxacin values (typically one to two dilutions) was less than that seen for tylosin and oxytetracycline. It is concluded that danofloxacin is highly active in vitro against all of the Mycoplasma species tested, and thus shows great potential for the treatment of respiratory and other infections caused by Mycoplasma species in cattle, pigs and poultry.

Animals↗
PubMed1993

A comparison of the efficacy of danofloxacin and tylosin in the control of Mycoplasma gallisepticum infection in broiler chicks.

Groups of chicks were infected with a virulent strain of Mycoplasma gallisepticum (MG) and treated with either danofloxacin or tylosin while one infected group was left untreated and a further group was uninfected and untreated. Control of clinical signs and mortality was better with danofloxacin than tylosin and there was significantly (P < 0.05) greater weight gain with danofloxacin at 21 days after infection. However at necropsy the prevalence of lesions of the airsac walls was similar in both groups. MG was recovered from fewer live chicks for the first week following treatment with danofloxacin, but at 2 weeks and at necropsy, at the termination of the experiment, it was recovered from a similar proportion of birds in both treated groups. This was reflected also in the serological results at the end of the trial.

Animals↗
PubMed1992

Efficacy of danofloxacin in the therapy of experimental mycoplasmosis in chicks.

Specific pathogen free day-old chicks were inoculated with a virulent strain of Mycoplasma gallisepticum. Birds received either danofloxacin (50 ppm), tylosin (500 ppm) or no medication in the drinking water from 24 hours after infection for three days. The effects of medication on mortality, weight gain, serology, lesions and reisolation of M gallisepticum 21 days following infection were studied. Treatment with danofloxacin and tylosin significantly decreased mortality and increased weight gain compared with infected unmedicated birds. Twenty-one days after infection, M gallisepticum was isolated from 96 per cent of unmedicated birds compared with only 6 per cent of danofloxacin-treated and 40 per cent of tylosin-treated birds, and the percentage showing positive serological tests was reduced from 100 per cent of unmedicated birds to 0 per cent of danofloxacin-treated and 29 per cent of tylosin-treated birds. In both cases, the proportion of positive birds from the danofloxacin-treated group was significantly lower than that from the tylosin-treated group. The occurrence of air sac lesions was also significantly lower in danofloxacin-treated than in tylosin-treated birds.

Animals↗
PubMed1990

The efficacy of danofloxacin in the therapy of pneumonia associated with Pasteurella species in housed calves.

The efficacy of danofloxacin, a novel third generation fluoroquinolone, was assessed in the treatment of pneumonia in housed calves on three farms in the FDR and Italy. Seventy three calves with clinical signs of acute pneumonia and rectal temperatures greater than 40 degrees C were treated with danofloxacin at a dose rate of 1.25 mg/kg for three or five days depending on response to treatment. The response in these calves was compared to that obtained in 77 calves treated with trimethoprim/sulpha. The clinical response achieved with danofloxacin was superior to that achieved with trimethoprim/sulpha and significantly fewer calves which received danofloxacin required five days treatment. Pasteurella haemolytica and, or P. multocida were isolated from the majority of calves prior to treatment. All isolates were sensitive to danofloxacin and over 90 percent were sensitive to trimethoprim/sulpha.

4-Quinolones↗
PubMed1983

Pneumothorax in the neonatal period.

The incidence of pneumothorax in the neonatal period is reviewed. Most infants who developed a pneumothorax were undergoing intermittent positive pressure ventilation. The most common underlying pathology associated with pneumothorax was idiopathic respiratory distress syndrome. This was the only condition in which a pneumothorax occurred in spontaneously breathing patients. The development of a pneumothorax was not significantly related to gestational age, birth weight, high ventilator inflation pressure, maximum fractional inspired oxygen concentration or the method of delivery. Evidence is presented to suggest that the development of a pneumothorax is not primarily a complication of ventilation but is due to the more severe pulmonary pathology of infants who require ventilatory assistance. Whatever the mechanism, prompt diagnosis and treatment mean that this common complication does not necessarily increase mortality.

Birth Weight↗