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Biomedical subjects

D Cummins

Publications and source records attributed to D Cummins.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

The in-vitro and ex-vivo effects of chloroquine sulphate on platelet function: implications for malaria prophylaxis in patients with impaired haemostasis.

Platelet aggregation responses were studied in platelet-rich plasma from six healthy volunteers before and 2 and 6 h after ingestion of 600 mg chloroquine sulphate. Apart from a mild reduction in height of aggregation response to 1 microgram ml-1 collagen 2 h post-drug ingestion (mean percentage of pre-drug values +/- s.e.m. = 87.8% +/- 4.0%; P = 0.04), no significant differences were observed in platelet responses to ADP (1 and 5 microM) or collagen (1 and 4 micrograms ml-1) at 2 or 6 h post-chloroquine compared to the pre-drug values. In vitro, drug concentrations approximately 1000 times greater than those used therapeutically were required for 50% inhibition of platelet aggregation and ATP release in response to 5 microM ADP, 1 microgram ml-1 collagen and 4 micrograms ml-1 collagen (IC50 concentrations +/- s.e.m. for inhibition of aggregation = 98.5 +/- 3.7, 53.5 +/- 56.4 and 113.0 +/- 6.2 mg l-1 respectively; IC50s +/- s.e.m. for inhibition of ATP release = 0.9 +/- 0.2, 14.7 +/- 4.0 and 23.0 +/- 5.3 mg l-1 respectively). These data provide no cause for concern in using chloroquine for malaria prophylaxis in patients with impaired haemostasis.

Adenosine Diphosphate↗
PubMed1989

Plasma from patients with severe Lassa fever profoundly modulates f-met-leu-phe induced superoxide generation in neutrophils.

A recurrent theme in studies of the pathology of fatal Lassa fever in man is the lack of histological lesions to explain disordered cell function and death. Recently, we demonstrated the existence of a factor in the plasma of patients with Lassa fever which markedly inhibits the aggregation responses of normal platelets in vitro. To assess whether this factor could mediate more global cellular dysfunction, we studied the effects of Lassa plasma on the respiratory burst of neutrophils. Thirteen of 15 samples from patients in the acute phase of Lassa fever profoundly inhibited the amount of superoxide generated by normal neutrophils in response to the chemotactic peptide, f-met-leu-phe (FMLP) (mean superoxide generated = 54.7 +/- 6.1% of control). In contrast, eight of nine samples from patients who had infections other than Lassa fever enhanced the neutrophil response to the peptide. All Lassa samples which inhibited the ADP-induced aggregation responses of normal platelets inhibited the neutrophil response to FMLP. Unlike the effect on platelets, however, the inhibition of neutrophils was only apparent when the cells were stimulated within 5 min of exposure to the plasma. The inhibition of neutrophils is not due to either interference with FMLP-neutrophil binding or an effect on the NADPH-oxidase, suggesting a suppression of signal transduction. Our data suggest the inhibitory factor in Lassa plasma has global effects on cellular function, and may play a central role in the pathogenesis of this often fatal illness.

Acute Disease↗
PubMed1989

A plasma inhibitor of platelet aggregation in patients with Lassa fever.

Previous studies have shown that haemorrhage in Lassa fever is associated with abnormal in vitro platelet aggregation and a high mortality. In Sierra Leone we studied platelet aggregation in healthy local subjects, patients with laboratory-confirmed Lassa fever and febrile patients in whom Lassa virus infection was excluded. There were no significant differences in the mean platelet counts of these groups. Patients with fulminant Lassa virus infection showed a gross depression of in-vitro platelet responsiveness to 1 and 5 microM ADP and 4 micrograms/ml collagen compared to other groups (P = 0.0004-0.0008 when compared to healthy controls, P = 0.002-0.0008 when compared to mild Lassa fever patients). When plasma samples from five of these patients were mixed 1:1 with control platelet-rich plasma, a marked inhibition of ADP-induced aggregation was observed. No inhibitory activity was detected in plasma obtained from healthy subjects or febrile control patients. The presence of inhibitor was strongly associated with the occurrence of haemorrhage (P = 0.03), depression of platelet aggregation (P = 0.004) and severity of Lassa fever (P = 0.007).

Adenosine Diphosphate↗