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Biomedical subjects

H Davies

Publications and source records attributed to H Davies.

At least 109 records · Page 6Linked to original sources

Coronary heart disease: the significance of coronary pathology in infancy and the role of mitogens such as vitamin D.

Intimal hyperplasia, damage to the internal elastic lamina, and proliferation of medial smooth muscle cells characterise the early response of an artery to damage. These changes are seen in the coronary arteries of the transplanted human heart, and are commonly seen in "normal" infants. Lipid incursion occurs only later, and the end-result is atheroma. These lesions of infancy are probably pathologic rather than physiologic, and are the precursors of later coronary heart disease. The early intimal and medial changes may be immune-engendered, encouraged by mitogens such as Vitamin D, and evolve in infancy as an aberration of the normal mechanisms controlling cellular proliferation.

Cell Division↗

Multiple idiopathic emboli in a full term neonate.

We report a case of multiple idiopathic emboli leading to cerebral infarction and to limb ischaemia in a full term neonate. The increased frequency of diagnosis of cerebral infarction is highlighted. Treatment of cerebral and limb emboli is discussed and the need for further research into the causes and treatment of cerebral infarction is stressed.

Arm↗

Interaction of campylobacter species with antibody, complement and phagocytes.

The opsonisation of four different campylobacter species for human neutrophils was studied using a chemiluminescence system and electron microscopy. Opsonisation of Campylobacter fetus, Campylobacter coli, and Campylobacter jejuni was mediated by antibody and enhanced by complement. Antibody was not, however, required for the phagocytosis of Campylobacter pylori because it activates the classical pathway of complement directly. This unusual property may be important in the pathogenesis of C pylori associated gastritis and duodenal ulcer.

Anaphylatoxins↗

Effects of posture on the distribution of pulmonary ventilation and perfusion in children and adults.

In the adult the distributions of ventilation and of perfusion show the same directional dependence on gravity. In children, however, the distribution of ventilation in response to gravity is the reverse of that seen in adults. The aim of the current study was to determine whether perfusion showed the same reversal in children or followed the adult pattern. Distribution of perfusion was measured with intravenous technetium-99m macroaggregated albumin and distribution of ventilation with inhaled krypton-81m. Eighteen children and seven adults were studied; they had been referred for lung scanning for various respiratory problems. The effect of gravity was examined by giving aliquots of macroaggregated albumin and 81mKr by inhalation to the subject in the supine and the lateral decubitus position. Counts in the dependent lung were compared with those in the upper lung. The dependent lung in the lateral decubitus position received more of the total perfusion than it did in the supine position in seven children with a normal chest radiograph (mean 7.0%, range 4.8-10.9% more) and in 11 children with an abnormal radiograph (mean 3.4%(0.1-10.0%)). Ventilation, however, changed in the opposite direction, falling by 7.1% (-3.2% to -12.8%) in five children with a normal chest radiograph and 11.2% (-2.8% to -19.3%) in eight children with an abnormal radiograph. Fractional V/fractional Q (an index of the ventilation:perfusion ratio) decreased in the dependent lung in the children when they moved from the supine to the decubitus position. The same directional change was recorded in adults, but it was significantly less than in the children, irrespective of whether the chest radiograph was abnormal. In children and adults with various respiratory problems the effect of posture on the distribution of perfusion is similar.

Adult↗

Sequence-specific binding of luzopeptin to DNA.

We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.

Antibiotics, Antineoplastic↗

[3H]ketanserin labels 5-HT2 receptors and alpha 1-adrenoceptors in human and pig brain membranes.

The binding characteristics of [3H]ketanserin (a reported selective radioligand for serotonin 5-HT2 receptors) and [125I]BE 2254 (which labels selectively alpha 1-adrenoceptors) were characterized in brain frontal cortex membranes of pig and man. Saturation experiments indicated that both radioligands label apparently a homogeneous class of binding sites in human and pig fontal cortex membranes. Competition experiments with [125I]BE 2254 using 17 agonists and antagonists showed monophasic and steep curves in human and pig frontal cortex membranes. The pharmacological profile of these sites is typical of alpha 1-adrenoceptors. In competition experiments with [3H]ketanserin, most of the tested compounds displayed shallow or biphasic curves. In particular, alpha 1-adrenoceptor-selective antagonists (prazosin, WB 4101, BE 2254...) displaced with nanomolar affinity about 15 and 40% of the specific [3H]ketanserin binding in human and pig frontal cortex membranes, respectively. The minor component of [3H]ketanserin binding correlated highly significantly with [125I]BE 2254 binding in both membrane preparations. The major component of [3H]ketanserin binding to pig and human frontal cortex membranes correlated significantly with [3H]ketanserin binding in rat brain cortex membranes (which is essentially to 5-HT2 receptors). The present data demonstrate that [3H]ketanserin in nanomolar concentrations binds significantly to alpha 1-adrenoceptors in human and pig frontal cortex membranes; this suggests a rather limited degree of selectivity of ketanserin for 5-HT2 receptors in pig and human tissues.

Adrenergic alpha-Antagonists↗

A simulation model for planning services for renal patients in Europe.

A discrete-event simulation model is being developed to provide information for national and regional health planners about the effect of different treatment policies and practices on the increasing numbers of patients with irreversible kidney failure. The simulation program, written in Pascal using Pascal-SIM, describes the activities of individual patients whose progress through treatment depends on their characteristics and treatment history, as well as on treatments availability. Programming techniques have been developed to cope with the multiple scheduling of patient entities and the resultant queue-management problems. In order to provide simulation runs on request, for any population group, appropriate data is selected from the European Dialysis and Transplant Association Registry data base for use in the simulation program. Results are shown on a computer screen while the simulation is running, and are saved for further analysis to provide feedback to the requesting organization.

Computer Simulation↗

Acute laryngeal obstruction in junctional epidermolysis bullosa.

A boy with junctional epidermolysis bullosa died from acute laryngeal obstruction at the age of 29 months, having been hoarse since early infancy. Post mortem studies showed gross narrowing of the laryngeal airway by cystic dilatations of the ducts of the seromucinous glands, and replacement of the laryngeal epithelium by oedematous granulation tissue. Laryngeal involvement appears to occur not infrequently in junctional epidermolysis bullosa, and contributes to its considerable mortality.

Acute Disease↗

[3H]ketanserin labels serotonin 5-HT2 and alpha 1-adrenergic receptors in human brain cortex.

The binding of [3H]ketanserin and [125I]BE 2254 [( beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone) was characterized in human brain cortex membranes. As observed in saturation experiments, [3H]ketanserin (a reportedly selective serotonin 5-HT2 ligand) and [125I]BE 2254 (a selective alpha 1-adrenergic antagonists) labeled, apparently, a homogeneous class of high-affinity recognition sites. Competition experiments performed with [125I]BE 2254 and a series of 20 structurally different compounds resulted in steep and monophasic competition curves. In contrast, competition curves of these compounds for [3H]ketanserin binding were often shallow or biphasic, suggesting a heterogeneity of the sites labeled by [3H]ketanserin. In particular, alpha-adrenoceptor-selective ligands (e.g., prazosin, BE 2254, WB 4101, phentolamine) showed clearly biphasic curves displacing about 20% of [3H]ketanserin binding with nanomolar affinity. On the other hand, cinanserin, a selective 5-HT2 antagonist, showed nanomolar affinity for 80% of the sites labeled by [3H]ketanserin, and micromolar affinity for the other 20%. There was a highly significant correlation between [125I]BE 2254 binding and the minor component of [3H]ketanserin in human brain cortex membranes (r = 0.910, p less than 0.0001, n = 20). The data show that [3H]ketanserin binds in the nanomolar concentration range (1.5-1.8 nM) to both 5-HT2 and alpha 1-adrenergic receptors. Similar results were obtained in rat and pig brain membranes. The data suggest that ketanserin possesses a rather limited degree of selectivity in human tissue.

Binding, Competitive↗

Once a day theophylline in chronic childhood asthma?

The therapeutic effects of either morning or evening administration of a once-daily controlled release theophylline preparation (Uniphyllin) were studied in 17 asthmatic children. Neither morning nor evening administration produced therapeutic plasma theophylline levels throughout 24h. Similarly, bronchodilation was not maintained during the same period. However, morning peak expiratory flow rates were significantly improved following evening dosage, suggesting a role for evening administration when nocturnal symptoms predominate.

Adolescent↗

Regional ventilation in infancy. Reversal of adult pattern.

There is evidence that in infants with unilateral lung disease, oxygenation improves when the good lung is uppermost--the reverse of the situation in adults. We performed krypton-81m ventilation scanning in 18 infants and very young children (11 days to 27 months old) with and without abnormal chest radiographs. Scanning was performed with the subject supine, in the left decubitus posture (right lung uppermost), and in the right decubitus posture (right lung dependent). Fractional ventilation to the right lung fell when that lung was dependent and rose when it was uppermost (P less than 0.001). This pattern was seen regardless of the appearance of the chest radiograph. The distribution of ventilation away from dependent lung regions represents a reversal of the adult pattern, which may be due to differences between infants and adults in lung mechanics and diaphragmatic function. This study adds further weight to the argument that infants and very young children with unilateral lung disease should be positioned with their normal lung uppermost to optimize gas exchange. It also offers a rational explanation for the observation that infants with unilateral gas trapping can be successfully treated by placing them so that the diseased lung is dependent.

Age Factors↗

Epithelial patchy necrosis in Crohn's disease.

Electron and light microscopic studies of the intestinal epithelium in Crohn's disease demonstrated localized areas of damage to the superficial epithelium, occurring without accompanying acute inflammation. In a blind study of rectal biopsy specimens from seven patients with Crohn's disease, four with ulcerative colitis, and four normal controls, this finding of patchy necrosis without acute inflammation was observed exclusively in four of the seven cases of Crohn's disease.

Biopsy↗

Bacteria and fungi in severe foot infection.

In a study of severe foot infection in 21 miners, an attempt was made to match nine clinical parameters with both bacteriological and mycological findings. Erythema was significantly more pronounced in the presence of dermatophytes but less pronounced in the presence of Gram-negative bacilli. No other clinical parameter differed in relation to the presence of particular microorganisms.

Bacteria↗

Further studies of the cytopathic effect in tissue cultures inoculated with CSF from patients with schizophrenia and other nervous system diseases.

Tissue cultures were inoculated with CSF from patients with schizophrenia and some other psychiatric and neurological illnesses. The CPE was readily seen in all 13 strains of human skin fibroblasts examined but could not be serially passaged. The results of retesting many specimens, either by the same worker or under full double blind conditions, usually agreed and thus indicate that the CPE was due to the CSF and not to non specific changes in the cultures. CPE was seen in cultures in which mycoplasmas could not be detected. Degenerated cultures show polymorphous nuclei with condensed nuclear chromatin and enlarged mitochondria with few cristae but virus particles were not identified. The physical properties of the agent in the CSF that induced the CPE were the same as those reported earlier for CSF from schizophrenic patients.

Adult↗

The Tongan story.

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Developing Countries↗