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Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 289 records · Page 16Linked to original sources

The prevalence and genetics of resistance to commonly used antimicrobial agents in faecal Enterobacteriaceae from children in Bangladesh.

The present study was undertaken to investigate the occurrence of antibiotic resistance in enteric flora in 64 children in rural Bangladesh over a 12-month period. The antibiotic resistance pattern of the isolates varied throughout the year and multiple resistance was highest during the post monsoon period. Seventy-three percent of children had isolates resistant to more than three antibiotics throughout the year. Resistance to streptomycin was highest (78%), followed closely by ampicillin (72%). Of 82 multiply resistant isolates, plasmid DNA was demonstrated in 75%. Plasmid sizes ranged between 3.7 and 110 MDa, the commonest plasmids were of 70, 98 and 110 MDa. Complete or partial resistance was transferred by conjugation from 52% of the isolates, most frequently by single plasmids. The commonest plasmid incompatibility group was F11-A (46%) followed by incompatibility group P (22%). Plasmids of molecular weight 98 MDa most often hybridized with F11-A probes and those of 110 MDa with H11 probes. Plasmids from 10 transconjugants were digested with restriction enzymes and digest patterns demonstrated the presence of common plasmids. The findings show that there is a diverse, and mobile, genetic pool of resistance genes in this rural community. This genetic reservoir is potentially transferable to enteric pathogens, with major implications for public health and diarrhoeal disease control.

Bangladesh↗

Human isolates of apramycin-resistant Escherichia coli which contain the genes for the AAC(3)IV enzyme.

Gentamicin-resistant Escherichia coli isolated at different periods from patients in two hospitals were tested for resistance to the aminoglycoside antibiotic apramycin. Twenty-four of 93 (26%) gentamicin-resistant isolates collected from the Royal Liverpool Hospital between 1981 and 1990 were resistant to apramycin. Thirteen isolates were highly resistant to apramycin (minimal inhibitory concentration (MIC) > or = 1024 micrograms/ml), were also resistant to gentamicin, netilmicin and tobramycin, and hybridized with a DNA probe derived from the aminoglycoside acetyltransferase (3)IV (AAC(3)IV) gene. The proportion of gentamicin-resistant isolates which had high level resistance to apramycin increased from 7% in 1981-5 to 24% in 1986-90. Twelve gentamicin-resistant E. coli from Guy's and St Thomas's Hospital isolated between 1977 and 1980 were also tested for resistance to apramycin. For five of these isolates the MICs of apramycin was 32-256 micrograms/ml. None was shown to have a conjugative plasmid carrying resistance to apramycin and only one hybridized with the DNA probe for the AAC(3)IV enzyme.

Acetyltransferases↗

Plasmid encoded multi-drug resistance in Salmonella typhi from Pakistan.

Twenty-five isolates of Salmonella typhi made from cases of typhoid fever during 1990-1991 in Rawalpindi and Islamabad, were examined. All isolates were resistant to chloramphenicol, ampicillin, tetracycline, streptomycin, sulphamethoxazole and trimethoprim, but were sensitive to nalidixic acid, ofloxacin, ciprofloxacin, cefuroxime and cefotaxime. A single large 98 MDa plasmid was identified in all the isolates. The plasmid was self-transferable and encoded resistance to chloramphenicol, ampicillin, tetracycline, streptomycin, sulphamethoxazole and trimethoprim. Restriction endonuclease analysis patterns after EcoRI and HindIII digestion of the 98 MDa multi-drug resistance plasmids from each of the S. typhi isolates and transconjugants were the same.

Drug Resistance, Microbial↗

Diarrhoea caused by Escherichia coli.

Since the mid-1940s, Escherichia coli has been recognized as a cause of diarrhoea. Subsequently it has been shown that at least five different pathogenic mechanisms are used to cause disease. Enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) produce a noninflammatory diarrhoea, whereas enteroinvasive E. coli (EIEC), enterohaemorrhagic E. coli (EHEC) and enteroaggregative E. coli (EAggEC) produce an inflammatory diarrhoea. ETEC are a major cause of diarrhoea in infants (up to three episodes per year) and travellers. They produce diarrhoea by attaching to the small intestinal mucosa and elaborate one or both of heat labile and heat stable toxins. EPEC attach firmly to the intestinal mucosa leading to dissolution of the brush border by inducing vesiculation of the microvilli. This process is known as attaching-effacement, and in the jejunum and ileum results in a loss of brush border disaccharidase enzymes and a large area of absorptive surface. EPEC are a major cause of summer diarrhoea in infants and neonatal diarrhoea. EIEC attach to colonic enterocytes, penetrate by an endocytotic mechanism and replicate therein. This results in necrosis and stripping of large areas of colonic mucosa and a dysentery similar to but usually less severe than Shigella dysentery. EHEC produce attaching-effacement to the terminal ileal and colonic mucosa and release the toxins, verocytotoxin (VT) 1 or 2. These kill colonic enterocytes and produce haemorrhagic colitis. In addition, VT can damage vascular endothelial cells, leading to haemolytic uraemic syndrome. The role of EHEC in diarrhoea in children in the tropics is not known. The most recently described group are the EAggEC. They damage and blunt colonic villi by haemorrhagic necrosis, although the precise pathogenic mechanisms are unclear. EAggEC are a major cause of chronic diarrhoea in children. Although certain O-serotypes are associated with the different enteropathic E. coli, serotyping is not sufficiently specific or sensitive for use as a diagnostic tool. Specific diagnosis is expensive and time consuming and depends upon demonstration of the pathogenicity trait, and the pathogenicity gene(s) or their gene product(s). At present, to undertake such testing is not recommended for routine diagnosis but is most useful when surveys of the aetiology of acute and chronic diarrhoea are undertaken.

Diarrhea↗

Ophthalmia neonatorum in Bangkok: the significance of Chlamydia trachomatis.

In a prospective 2-month case-controlled study, 17 cases of neonatal conjunctivitis were diagnosed. A statistically significant association between neonatal conjunctivitis and the presence of Chlamydia trachomatis (five cases) and Staphylococcus aureus (five cases) was shown. No cases of gonococcal conjunctivitis were found, perhaps because of the routine use of silver nitrate (1%) drops. C. trachomatis conjunctivitis could not be diagnosed on clinical grounds, nor was examination of Giemsa-stained conjunctival scrapes sufficiently sensitive to detect all cases. In order to prevent the long-term morbidity of C. trachomatis infection in both mother and child, specific aetiological diagnosis using immunodiagnostic or cultural procedures is required.

Bacteriological Techniques↗

Chemoprophylaxis of bacterial meningitis.

Bacterial meningitis continues to be a life-threatening disease and an important cause of severe disability in otherwise healthy individuals. This article reviews the aspects related to the prevention of secondary cases. Our understanding about the factors leading to an epidemic and the identification of high risk groups remains limited. For this reason, chemoprophylaxis can be used only for the prevention of secondary cases once an index case has been identified. The objectives of prophylaxis are threefold: (i) to eliminate nasopharyngeal carriage in household contacts; (ii) to prevent contacts from acquiring the disease and (iii) to treat infection in those incubating the disease. Chemoprophylaxis can only achieve the first of these objectives. Nasopharyngeal carriage of meningococci and Haemophilus influenzae can be eradicated with the use of antibiotics and their advantages and disadvantages are discussed. Prophylaxis should be given to household members and kissing and saliva-exchanging contacts of a case of meningococcal meningitis. The decision to give prophylaxis to extended family contacts, close neighbour contacts or children attending day-care centres where a case has occurred is controversial. It does not alter the course of an epidemic and close contacts are liable to become reinfected soon after prophylaxis. Prophylaxis of H. influenzae should be given to households in which there is at least one child (other than the index case) under 48 months of age. There is no agreement on the need to provide chemoprophylaxis to children in day-care centres because the risk of secondary infections is uncertain. An alternative to chemoprophylaxis is protective chemotherapy which can prevent the development of meningitis in individuals incubating the disease.

Anti-Bacterial Agents↗

Management of bacterial meningitis.

In developed countries the mortality from bacterial meningitis acquired outside the neonatal period is relatively low. In contrast, in developing countries it is often higher (20%-40%). In developed countries despite (and perhaps because of) the introduction of increasingly potent antimicrobials, the morbidity of bacterial meningitis has remained high. For example, up to 25% of patients with Haemophilus influenzae meningitis have some form of neurological deficit. Neisseria meningitidis is the major cause of bacterial meningitis in many areas of the world. A clone of Group A meningococcus has spread from China to cause the most recent major epidemic in Sub-Saharan Africa. Group B meningococcal infections causing sporadic meningitis are increasing in parts of Europe and South America. The mortality from meningococcal disease is greatest when there is a septicaemic component to the infection. Although antimicrobial chemotherapy is of major importance some adjuncts to therapy are beneficial. High dose corticosteroid therapy has been shown to decrease mortality in pneumococcal meningitis in an uncontrolled study and to speed recovery and decrease neurological sequelae in H. influenzae meningitis. Nevertheless to prevent infection would be of greater benefit. Prevention can be achieved by either chemoprophylaxis or immunoprophylaxis. Although safe and effective vaccines are available to prevent pneumococcal, H. influenzae (Hib) and Groups A and C meningococcal meningitis; apart from the protein conjugate Hib vaccine they are less effective in children under two years of age. There is no effective vaccine to protect against group B meningococcal meningitis.

Adolescent↗

Cowpox can mimic anthrax.

We report a patient suffering from cowpox infection, in whom the clinical features mimicked those of anthrax. The infection may have been acquired as a result of contact with a rodent.

Adolescent↗

Effect of cytotoxic drugs on mature neutrophil function in the presence and absence of granulocyte-macrophage colony-stimulating factor.

The effects of the cytotoxic drugs, adriamycin, cyclophosphamide, daunomycin (daunorubicin), prednisolone, actinomycin D, azacytidine and vincristine at concentrations of 1 microM on mature neutrophil function were examined. Up to 5 h incubation with adriamycin, azacytidine, cyclophosphamide, daunomycin and prednisolone had no effect on either luminol chemiluminescence or superoxide secretion. However, after 15 min or 1 h (but not 5 h) incubation vincristine enhanced fMet-Leu-Phe stimulated chemiluminescence, whilst after 5 h incubation with actinomycin D the ability of neutrophils to generate reactive oxidants in response to all stimuli tested was impaired: after 5 h incubation with adriamycin reactive oxidant production was also impaired, but only when fMet-Leu-Phe was used as stimulant. All of the drugs tested except azacytidine inhibited neutrophil oxidant production after 5 h incubation in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Actinomycin D and cyclophosphamide also inhibited GM-CSF stimulated protein biosynthesis. These data indicate that cytotoxic drugs may compromise the potentially beneficial effects of CSFs on mature neutrophil function during therapy.

Antineoplastic Agents↗

Bacterial factors in the formation of renal scars. An experimental study on the role of Escherichia coli P-fimbriation and hydrophobicity.

A model capable of comparing the effects of bacterial virulence factors on renal scarring in vivo has been developed using the female piglet. By creating, at open surgery, unilateral vesicoureteric reflux (VUR) and quantifying scarring both by uptake of an isotope bound to functioning renal parenchyma and by planimetry of the surface area scarred, the effects of 2 organisms, a P-fimbriate Escherichia coli and an E. coli K1 have been compared. The P-fimbriate E. coli was shown to express P-fimbriae in freshly voided urine, was more hydrophobic and produced smaller scars. This indicates that neither the hydrophobicity nor P-fimbriation of the organism causing urinary tract infection (UTI) is of prime importance for the development of renal scars and is evidence against the "big bang" theory for the development of renal scars. Studies on the association of UTI with VUR showed that infection with both E. coli under study led to VUR on the side contralateral to the side undergoing surgery. It seems likely that a non-specific effect of UTI, such as bladder oedema, is responsible for this acquired VUR. An effect of the 2 bacteria under study on the lower urinary tract was observed in that infection with the P-fimbriate E. coli allowed the retention of an intravesical wax plug, whereas infection with E. coli K1 did not. Epidemiological data have shown that the majority of upper urinary tract infections in children are associated with UTI by P-fimbriate organisms. Such an association may be explained in part by an effect of P-fimbriate bacteria on lower urinary tract function rather than an effect on the upper urinary tract.

Animals↗

Reconsideration of the roles of urinary infection and vesicoureteric reflux in the pathogenesis of renal scarring.

In an experimental study of female piglets with surgically created unilateral vesicoureteric reflux, Escherichia coli were inoculated into the bladder and, at later sacrifice, bacterial culture was undertaken of renal parenchyma from the refluxing and non-refluxing kidneys. Positive cultures of the same E. coli were obtained from 33% of refluxing kidneys with pyelonephritic renal scars, 23% of refluxing kidneys without scars and 21% of non-refluxing kidneys. Although other aspects of the experiments confirmed that a combination of urinary infection, vesicoureteric reflux and intra-renal reflux is a necessary precondition for renal scarring, these findings indicate that reflux plays a role in the pathogenesis of renal scarring over and above a means whereby pathogens gain access from the lower urinary tract to the renal substance. Possible mechanisms are discussed.

Animals↗

Updating the nurse's bedside manner.

The current tendency for nurses to be on a first name basis with their patients and to wear less professional clothing provides new metaphors for interpreting nurses' work status. We argue that this prevailing social informality in communications and dress perpetuates themes that diminish the professional image of nurses, masks the cognitive nature of their work, threatens nurses' therapeutic effectiveness, and continues to reinforce the hierarchical relationship between nurses and physicians. Strategies are presented to help nurse educators, administrators, and clinicians transform nurses' work environments into clinical settings that enhance their professional presentation.

Clothing↗

Variation in serum C-reactive protein across the clinical spectrum of meningococcal disease.

In a multicentre prospective study, 124 cases of meningococcal disease were classified into the clinical categories, meningitis alone (n = 15), meningitis and septicaemia (n = 79) and septicaemia alone (n = 30). A further 60 children referred with other illnesses served as controls. Serial measurements of serum C-reactive protein (admission, day 1, day 2, days 5-7) were compared. Children with septicaemia had significantly lower C-reactive protein levels on admission than those with meningitis alone or meningitis and septicaemia which were unexplained by differences in the duration of the presenting illness or severity of the disease. Within each clinical category of meningococcal disease, significant changes in C-reactive protein concentration occurred during the course of the disease. Four control children had other types of septic meningitis: admission C-reactive protein concentrations did not differ from those with meningitis or meningitis and septicaemia, but were significantly higher than those with septicaemia alone. The other 56 patients had a significantly lower admission C-reactive protein concentration compared with all cases of meningococcal disease. For the diagnosis of meningococcal disease, admission C-reactive protein levels of > or = 40 mg/l had a sensitivity of 79%, specificity of 80% and positive predictive value of 87%. For the prognostic prediction of death in meningococcal disease (or meningococcal disease with shock) CRP < 100 mg/l on admission had a sensitivity of 69% (69%), specificity of 50% (56%) and positive predictive value of 18% (53%). In children with suspected meningococcal disease, serum C-reactive protein, measured on admission, has diagnostic value but not prognostic value.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Reactive Protein↗

Distribution of O-acetylated sialomucin in the normal and diseased gastrointestinal tract shown by a new monoclonal antibody.

AIMS: To produce and characterise a monoclonal antibody specific for O-acetylated sialomucin and to assess its use in immunohistochemistry on a panel of normal and diseased intestinal tissue samples. METHODS: Mouse monoclonal antibodies were developed following immunisation with highly purified human colonic mucin. One of these (MMM-17) showed strong binding to mucin throughout the normal colon with relative lack of binding to colon cancer tissue. The binding epitope of MMM-17 was then characterised by screening for agglutination activity against a panel of human and animal erythrocytes and by assessment of its binding to a range of normal and chemically treated slot blotted mucins. Further immunohistochemical studies were then performed on formalin fixed, normal, and diseased human intestinal samples. RESULTS: Binding of MMM-17 to slot blotted human colonic mucin was reduced by 38 (SD 14%) (n = 4) by alkali treatment of the mucin, sequential alkali and sialidase treatment completely abolished binding. Sialidase treatment alone, however, caused only an 11 (11%) reduction in binding. MMM-17 failed to agglutinate any human, rabbit, rat or mouse erythrocytes. These findings were compatible with specificity of MMM-17 for sialomucins O-acetylated at the C-7 or C-8 positions on the sialic acid. Strong staining by MMM-17 was found in all goblet cells throughout all 40 normal colonic and rectal samples studied, but staining was absent in seven of 13 colorectal carcinomas. Normal duodenum (n = 16) and normal ileum (n = 3) all showed occasional positive goblet cells. The normal gastric antral mucosa was generally negative B MMM-17, but in all of 15 cases of gastritis with intestinal metaplasia the metaplastic glands were strongly positive for MMM-17. CONCLUSION: Monoclonal antibody MMM-17 has specificity for O-acetylated sialomucins and its binding depends both on the position of O-acetylation and on the adjacent oligosaccharide structure. Preliminary studies using the antibody on archival tissue samples support the previous reports of reduced O-acetylation in colon cancer demonstrated by indirect histochemistry and show the neo-formation of O-acetylated sialomucin in intestinal metaplasia in the stomach.

Animals↗

HBsAg and aflatoxins in sera of rural (Igbo-Ora) and urban (Ibadan) populations in Nigeria.

The purpose of this study was to screen for the presence of hepatitis B surface antigen and aflatoxins in the sera of 100 non-hospitalized individuals from the rural population of Igbo-Ora and 89 non-hospitalized individuals from the urban population of Ibadan, Nigeria. Hitherto, such a study as this has not been undertaken in this environment. The proportions of hepatitis B surface antigen carriage and serum 'pathologic' levels of aflatoxins were high (47-49%, 8.2-9.0% respectively) but varied very little between the two different populations sampled. These findings indicate that determined efforts should be instituted to reduce or eliminate hepatitis B virus infection and aflatoxin contamination of high risk foodstuffs from this environment.

Adolescent↗