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Biomedical subjects

D Cummins

Publications and source records attributed to D Cummins.

At least 19 recordsLinked to original sources
PubMed1992

Delivery of antiplaque agents from dentifrices, gels, and mouthwashes.

Antiplaque agents delivered from toothpastes, gels, or mouthrinses can augment mechanical oral hygiene procedures to control the formation of supragingival plaque and the development of early periodontal disease. Clinically effective antiplaque agents are characterized by a combination of intrinsic antibacterial activity and good oral retention properties. The overall oral retention of an antiplaque agent is determined by the strength and rate of association of the agent with its receptor sites and the accessibility of these sites. The substantivity of an antiplaque agent and its clearance from the oral cavity are determined by the rate of dissociation of the agent from the receptor sites and the salivary composition and flow rate. Positively charged and non-charged organic molecules, metal ions, enzymes, and surface-active agents have all been considered as antiplaque agents. To exert clinical antiplaque activity, an antimicrobial agent must be formulated in a chemically compatible delivery vehicle to give optimal release and uptake to the sites of action in a biologically active form during its time of application. In principle, antiplaque activity may be enhanced by combining antimicrobial agents with broadly similar, but complementary, modes of action. Alternatively, the activity of a single agent may be increased by use of a retention aid to enhance oral substantivity. Substantial evidence exists to demonstrate the validity of the first approach. However, there are few data, as yet, to support the effectiveness of the second. The oral mucosa is the bulk retention site for all clinically proven antiplaque agents. Plaque, the pellicle-coated tooth surface, and saliva are probably all sites of biological action. A detailed understanding of the interactions between agents and the various receptor sites, and of the importance of these receptor sites to biological activity, is generally lacking.

Anti-Infective Agents, Local↗
PubMed1992

Lassa fever encephalopathy: clinical and laboratory findings.

Clinical and laboratory findings are reported in nine patients who developed acute encephalopathy during the course of Lassa fever. The encephalopathy manifested 3-17 days after disease onset with confusion, followed rapidly by tremor (seven patients), grand mal convulsions (seven), abnormal posturing (three) and coma (eight); focal neurological signs and evidence of raised intracranial pressure were not seen. Eight patients died, most commonly from respiratory arrest following a protracted fit. Development of encephalopathy did not correlate with the presence of virus in cerebrospinal fluid (CSF), nor with virus antibodies in CSF and/or serum; thus, neither direct cytopathic nor immune-mediated mechanisms seem to be involved in its pathogenesis.

Adolescent↗
PubMed1991

Penicillin prophylaxis in children with sickle cell disease in Brent.

OBJECTIVE: To assess compliance with oral penicillin prophylaxis in children with sickle cell disease and identify possible reasons for poor compliance. DESIGN: Closed questionnaires given to parents of children with sickle cell disease and general practitioners in Brent. Urine samples from 23 children were tested for penicillin. SETTING: Paediatric haematology clinic, Central Middlesex Hospital, and general practices in Brent. SUBJECTS: 50 children (aged less than or equal to 16) attending clinic with sickle cell disease over six months (33 HbSS, 12 HbSC, five HbS beta thalassaemia). 30 general practitioners: 15 with the greatest number of patients with sickle cell disease on the Brent register; 15 selected randomly from family practitioner committee's list. MAIN OUTCOME MEASURES: Reported compliance with and awareness of importance of penicillin prophylaxis. Results of urine tests for penicillin. RESULTS: 31 parents claimed that their children received penicillin every day and 19 that they received it most days (greater than or equal to 5 days a week). Penicillin was detected in only 10 of 23 urine samples tested. Parents and doctors seemed not to appreciate the importance of treatment: only eight parents were aware of the risk of death if penicillin were discontinued, and 16 doctors were unaware that regular penicillin prophylaxis prevents pneumococcal septicaemia and death in these children. CONCLUSIONS: Education for families with children with sickle cell disease must be improved. Specialised information and training are needed for doctors working in areas with a high prevalence of the disorder.

Administration, Oral↗
PubMed1991

Rat retinal ganglion cells in culture.

A stable cell culture system of identified retinal ganglion cells would facilitate the investigation of cellular mechanisms of damage from glaucoma and other disorders. We have developed a reliable technique to culture retinal ganglion cells on a glial cells monolayer which extends viability and promotes extensive neurite outgrowth. Dissociated retinal cells from 5-7-day-old Sprague-Dawley rats were cultured on glial monolayers derived from rat cerebral hemispheres. Retinal ganglion cells were labeled with retrograde fluorescent markers injected into the superior colliculus or in culture with monoclonal antibody to Thy-1 antigen. Since Thy-1 antigen is not entirely specific for retinal ganglion cells, and fluorescent markers fade in older cultures, the identity of Thy-1 marked cells was confirmed with whole-cell electrophysiologic recordings. Labeled, physiologically intact retinal ganglion cells were identified for at least 31 days in culture. Many retinal ganglion cells showed neurite elongation of 2 mm or more and developed complex intercellular networks. This cell culture system may be used to form the basis for future studies of the electrophysiology and transport properties of retinal ganglion cells under normal culture conditions and under adverse conditions such as those that mimic ischemia or mechanical deformation.

Action Potentials↗
PubMed1991

Arenaviral haemorrhagic fevers.

Three arenaviruses--Lassa, Junin and Machupo--cause severe haemorrhagic disease in humans: Lassa fever, Argentine haemorrhagic fever and Bolivian haemorrhagic fever, respectively. These conditions are a source of considerable economic hardship in endemic areas and remain a worldwide concern for public-health officials. They are characterised by an insidious onset of influenza-like symptoms followed, in severe cases, by a generalised bleeding diathesis, encephalopathy and death. Central to studies of their pathogenesis is evidence for cellular dysfunction disproportionate to overt histopathology. Recent studies of patients with Lassa fever indicate that platelet and possibly endothelial-cell dysfunction play an important role in the bleeding tendency. The platelet defect appears to be mediated by an inhibitory factor in plasma; the nature of this is uncertain but it seems to be neither viral protein nor virus antibody. A similar inhibitor has since been demonstrated in patients with Argentine haemorrhagic fever. Plasma from patients with Lassa fever also profoundly modulates the amount of superoxide generated by normal neutrophils in response to the chemotactic peptide f-met-leu-phe, suggesting the inhibitor(s) has global effects on cellular function. These findings may have important implications for future therapeutic strategies.

Hemorrhagic Fever, American↗
PubMed1991

Zinc citrate/Triclosan: a new anti-plaque system for the control of plaque and the prevention of gingivitis: short-term clinical and mode of action studies.

A dentifrice based upon the additive anti-plaque effects of zinc citrate and Triclosan has been developed and optimised for clinical activity. In 16-h and 4-day plaque growth inhibition studies, zinc citrate/Triclosan inhibited plaque accumulation significantly more than either agent alone. The effect on the development of gingivitis has been demonstrated in a 21-day experimental gingivitis study. ZCT/Triclosan reduced the development of gingival bleeding sites by significantly more than ZCT alone, suggesting that the system has the potential to give a gingival health benefit in a 6-month unsupervised brushing study. Zinc and Triclosan employ multiple modes of antimicrobial action and these result in reduced growth, inhibition of glucose uptake and metabolism and modified virulence of periodontal pathogens. Importantly, the effects of zinc and Triclosan are additive and complementary. Oral substantivity is a pre-requisite of any agent for anti-plaque activity in vivo. Pharmacokinetic data demonstrate that approximately 30% of the zinc and Triclosan dosed is retained immediately after brushing. Saliva decay curves indicate that Triclosan is cleared more quickly from the mouth than zinc, consistent with the physicochemical properties of these agents. Triclosan is present in plaque for at least 8 h and in the oral mucosa for at least 3 h after brushing.

Anti-Infective Agents↗
PubMed1991

Exchange transfusion of a patient with fulminant Lassa fever.

We report a patient with fulminant Lassa fever who responded dramatically to a 2.5-litre exchange transfusion of whole blood. On admission he was semicomatose with facial oedema and oral haemorrhage; his platelets showed markedly depressed aggregation to ADP; and his plasma inhibited the aggregation responses of normal platelets in vitro. Exchange transfusion resulted in rapid clinical improvement, recovery of platelet function, and disappearance of platelet-inhibitory activity in plasma. The patient died 2 weeks later from an acute encephalopathy. His initial response was sufficiently impressive to suggest that further evaluation of this therapeutic approach is justified in selected patients with overwhelming Lassa virus infection.

Adult↗
PubMed1991

Delayed haemolytic transfusion reactions in patients with sickle cell disease.

We describe two cases which illustrate the difficult diagnostic and therapeutic problems posed by delayed haemolytic transfusion reactions in patients with sickle-cell disease. The cases emphasize the need for meticulous phenotypic and serological assessment of sickle-cell patients prior to transfusion therapy.

Adolescent↗
PubMed1991

Inhibition of acid production by Streptococcus mutans NCTC 10449 by zinc and the effect of metal speciation.

Ionic zinc as zinc sulphate was strongly inhibitory to acid production from glucose by washed cell suspensions of Streptococcus mutans NCTC 10449 in a pH-stat assay (50% inhibition at 0.1 mM zinc). Zinc was adsorbed to the cells (up to 8 micrograms/mg cells). Several other zinc salts that dissociated to free zinc ions were also strongly inhibitory. Zinc in a partially complexed form as zinc citrate was less strongly inhibitory (50% inhibition at 0.2 mM zinc), and adsorption of zinc was lower (up to 3 micrograms/mg cells). Stoichiometric addition of ethylenediaminetetra-acetic acid (EDTA) to assays containing zinc sulphate completely removed inhibition and adsorption of zinc. A good correlation between inhibition of acid production and adsorption of zinc was found, and zinc adsorption was correlated with the levels of free zinc ion in the assay mixtures. The strongly anionic complexes of zinc, Zn(CIT)-, Zn(CIT)4-(2), and Zn(EDTA)2-, were not inhibitory and did not adsorb to the bacterial cells.

Acids↗
PubMed1991

The isolated ciliary bilayer is useful for studies of aqueous humor formation.

An intact ciliary epithelial bilayer has been isolated from the rabbit eye by perfusion, microsurgical dissection, and recovery techniques. Vital subcellular organelles and intercellular junctions of this epithelial bilayer preparation are very well preserved. The total electrical resistance of the epithelial bilayer is 350 ohms, and the transepithelial potential is 650 microV, nonpigmented epithelium side negative. The electrical resistance is reduced by 0.2 mM EGTA and the transepithelial potential reduced by 0.1 mM ouabain. Bicarbonate depletion at a constant pH of 7.4 rapidly and significantly reduces the transepithelial potential. Carbonic anhydrase inhibitors decrease transmembrane potential by as much as 30%. These morphologic and physiologic experiments authenticate the validity of this bilayered epithelial preparation for future use in detailed studies of the mechanism of aqueous humor formation.

Animals↗
PubMed1991

Anti-plaque dentifrices: current status and prospects.

A dentifrice can, in principle, be an effective delivery vehicle for anti-plaque agents, provided bioavailability of the agent concerned can be achieved, because the agent is applied and delivered at the site of action and favourable patient compliance can be obtained. It is widely assumed that anti-plaque agents need to be retained in the oral cavity after application ('substantivity'). To use a dentifrice as a dosing vehicle successfully the anti-plaque agents have to be compatible with the dentifrice formulation to achieve release from the formulation and subsequent retention of the anti-plaque agent after application. Various anti-plaque agents have been described, such as quarternary ammonium compounds (e.g., chlorhexidine), metal ions and phenolic agents. Recently progress has been achieved with a selection of compatible anti-plaque agents for inclusion in a dentifrice such as metal ions and non-charged phenolic agents. Studies on long-term unsupervised brushing have shown favourable anti-plaque and anti-gingivitis activity from anti-plaque agents dosed from a dentifrice [corrected].

Dental Plaque↗
PubMed1990

A plasma inhibitor of platelet aggregation in patients with Argentine hemorrhagic fever.

Hemorrhage in patients with Lassa fever is associated with the presence of a circulating plasma inhibitor of platelet aggregation. This study was to determine whether patients with Argentine hemorrhagic fever (AHF) develop a similar inhibitor. Normal platelets showed significantly weaker aggregation responses to a sub-maximal dose of adenosine diphosphate (ADP) when mixed with plasma from 10 patients with AHF (mean percent of control +/- 1 SE = 57.2 +/- 6.7%) compared to those mixed with plasma from 9 viral control patients (79.5 +/- 4.1%; P less than 0.05) and 9 febrile patients with septicemia (103.8 +/- 3%; P less than 0.001). Plasma from 3 patients with severe AHF inhibited in a dose-dependent fashion the aggregation responses of normal platelets to collagen, sodium arachidonate, a calcium ionophore (A23187), and ristocetin; none of 4 samples from convalescent AHF patients showed this inhibitory activity. The platelet inhibition was sudden in onset and unaffected by a 30 min pre-incubation, not neutralized by convalescent plasma with high titer antibody to Junin virus, and abolished after heating plasma from an AHF patient at 56 degrees C for 30 min. Hemorrhage in AHF is associated with the presence of a circulating inhibitor of platelet aggregation, and disturbed hemostasis in arenavirus-induced hemorrhagic fevers may have a common basis.

Adenosine Diphosphate↗
PubMed1990

Lassa fever.

Lassa fever is an acute viral illness which causes considerable morbidity and mortality in West Africa. The risk of importing the disease into the UK is small but real, and it continues to be a worldwide concern among public health officials. This article summarizes its epidemiology and clinical presentation, and discusses current theories of its pathogenesis.

Africa, Western↗