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Biomedical subjects

A H Williams

Publications and source records attributed to A H Williams.

At least 19 recordsLinked to original sources

Teicoplanin in open fractures: a preliminary report.

The occurrence of infection following open fractures varies with the severity of the fracture and associated soft tissue damage. In order to study the effect of antibiotics given prophylactically, teicoplanin has been used in a prospective study. On admission, fractures were graded according to the severity of the tissue damage: Type I--soft tissue injury less than 1 cm Type II--soft tissue injury more than 1 cm. Type III fractures characterized by extensive soft tissue and bone damage were not included in the study. Type I patients were given a single dose of teicoplanin, 400 mg i.v.; Type II patients were given a single dose of teicoplanin, 400 mg i.v., followed by two further intravenous injections at 12 and 24 hours. Patients were assessed for the presence of wound and bone infections and follow up was for 1 year. Preliminary results, predominantly from Type II fractures involving long bones, show that teicoplanin is effective in lowering the incidence of infection following open fractures.

Adolescent

Infections due to gram-positive organisms in children: possible role for teicoplanin.

The disruptive effect on, and potentially hazardous exposure to nosocomial infection, together with the relative cost of hospitalization, of children favours the need for ambulatory care. An increasing proportion of infections in children are due to beta-lactam resistant Gram-positive organisms. Teicoplanin is proposed as a suitable candidate for treating paediatric patients with serious Gram-positive infections in hospital or ambulatory care. The experience acquired in children is still limited. However, over 200 paediatric patients have been treated with once or twice daily im or iv teicoplanin in daily doses of 3-10 mg/kg. The main clinical diagnoses were skin and soft tissue infections, skeletal infections and septicaemia. The drug was safe and clinical efficacy was greater than 90%. Comparative studies with defined uniform protocols are now required to assess the potential of this drug.

Anti-Bacterial Agents

Teicoplanin monotherapy of serious infections caused by gram-positive bacteria: a re-evaluation of patients with endocarditis or Staphylococcus aureus bacteraemia from a European open trial.

We have examined case records for patients who received teicoplanin alone for endocarditis or Staphylococcus aureus bacteraemia. All patients with streptococcal endocarditis were cured (viridans group 14/14; Group D 4/4). Cure rates for other organisms were: Enterococcus faecalis 3/5; S. aureus 5/10 and coagulase negative staphylococci 2/3. Doses for six patients who failed because of poor response were 3.3-4.2 mg/kg. Teicoplanin treatment cured 41/48 patients with S. aureus bacteraemia; treatment failed in two patients because of adverse events. Doses in the remaining treatment failures were 2.1-5.0 mg/kg. In comparison, 48 patients in Dundee hospitals received ten different drugs in 20 combinations for S. aureus bacteraemia; 29 patients received cloxacillin or flucloxacillin but initial doses varied from 0.25-2.0 g. We conclude that the European database does provide evidence that teicoplanin monotherapy is effective for serious infection with Gram-positive bacteria. Doses for staphylococcal infection should probably be at least 6 mg/kg. The upper limit of the teicoplanin dosage range remains to be determined but there is evidently considerable confusion about appropriate regimens for 'standard' therapy.

Anti-Bacterial Agents

A review of the safety profile of teicoplanin.

Safety of teicoplanin has been assessed in 3377 patients treated in Europe up to the end of June 1990. One or more adverse events were experienced by 10% of patients. Age and teicoplanin dose had no significant effect on the incidence or type of adverse event. In comparative trials the incidence and profile of adverse events to teicoplanin have been similar to those seen with beta-lactam therapy. Impaired renal function occurred consistently more frequently with vancomycin therapy than with teicoplanin therapy, particularly when these drugs were co-administered with aminoglycosides. Severe skin reactions have not been reported with teicoplanin, which, unlike vancomycin, does not cause infusion rate-related release of histamine. These data provide further evidence that teicoplanin is safer than vancomycin and does not have dose-related adverse effects in the dose range 3-10 mg/kg.

Animals

Do patients presenting to accident and emergency departments have low serum anticonvulsant concentrations?

It is often felt that poorly controlled epileptic patients, who are taking anticonvulsant medication, are over represented in A&E departments compared to the general population. This A&E based study set out to determine whether such patients do have inadequate serum anticonvulsant levels, when they present following a seizure, to A&E departments. All epileptic patients, taking medication, who presented to the A&E departments of St. Bartholomew's and Hackney Hospitals, London, over a 4-month period were studied. Serum anticonvulsant concentrations were measured on their arrival in the departments. Forty-six patients were studied. Only 21% of anticonvulsant drug concentrations were within 'therapeutic' ranges. A total of 66% were below 'therapeutic' ranges and 13% were potentially toxic. The implication of these findings is discussed.

Adolescent

Modulation of expression of MHC antigens in the kidneys of mice by murine interferon-alpha/beta.

We have analyzed the effects of interferon-alpha/beta on MHC expression in the murine kidney, and compared these results with the MHC modulating effects of interferon-gamma. Natural murine interferon-alpha/beta was administered to B10.BR mice (H-2k), i.p., twice daily for 3 days. Expression of MHC antigens was assessed on day 4 by immunoperoxidase staining with biotinylated monoclonal antibodies to class I (KkDk) and class II (I-Ak) antigens. Interferon-alpha/beta significantly decreased the number of class II-positive renal cortical dendritic cells from 62.0/mm2 to 12.6/mm2 (P less than 0.001). A similar but less dramatic decrease was seen in cardiac dendritic cells. Little or no change in class II expression was observed in proximal tubules or glomeruli. Interferon-alpha/beta induced marked class I staining in the glomerulus, arterial endothelium, and Bowman's capsule. Proximal tubule cells also showed increased class I expression, but were less responsive than glomeruli. Thus, the effects of interferon-alpha/beta contrast with those of interferon-gamma, which increases class II expression on proximal tubules, induces relatively more class I expression in proximal tubules than glomeruli, and increases class II-positive dendritic cells. Furthermore, these results suggest that treatment with interferon-alpha/beta may have a complex effect on the immune response to a renal allograft due to its differential effects on class I and class II cell surface expression.

Animals

Direct single-reagent fluorescence polarisation immunoassay for valproic acid in serum.

A fluorescence polarisation immunoassay for quantitating serum concentrations of valproic acid was developed and validated. Its low molecular weight and lack of structural features caused difficulties in producing suitable antibodies. However, success was achieved using 2-propyl-6-aminohexanoic acid to make the fluorescein-labelled drug and two immunogens, the first using glutaraldehyde to link the drug derivative to keyhole limpet haemocyanin, and the second by carbodiimide activation of cellulose hydroxyl groups and coupling them to the drug derivative and killed Mycobacteria. It was found that both immunogens produced a good antibody response in sheep. The antibodies were highly specific and the assay results correlated well with an in-house gas-liquid chromatographic method.

Chromatography, Gas

The use of a new glycopeptide antibiotic, teicoplanin, in the treatment of bacterial endocarditis.

Teicoplanin, a new glycopeptide antibiotic, has been used to treat twelve patients with bacterial endocarditis due to Gram-positive organisms. Teicoplanin has activity against Gram-positive bacteria similar to vancomycin but therapeutic levels are maintained by a single daily dose, given as an intravenous bolus. Of six patients with native valve infections, two cases, due to viridans streptococci, were successfully treated with teicoplanin alone and two others, caused by Streptococcus faecalis, were cured by combinations including teicoplanin. One of these patients sustained high tone hearing loss during treatment. The remaining two patients were drug addicts with endocarditis due to Staphylococcus aureus which recurred despite repeated multiple therapy. Of six prosthetic valve infections, antibiotic combinations including teicoplanin cured three cases, caused by streptococci. Infection persisted or treatment was curtailed in three cases of Staphylococcus epidermidis endocarditis. In this small open study, teicoplanin appeared as effective as vancomycin in the treatment of endocarditis but had the considerable advantage of ease of administration.

Anti-Bacterial Agents

Teicoplanin in the treatment of infection caused by gram-positive organisms.

Teicoplanin was used to treat 94 hospital in-patients of confirmed or presumed Gram-positive infections over a period of 12 months. Eighty-five patients were subsequently found to be evaluable; 31 had soft tissue infections, 10 endocarditis, 8 urinary tract infections, 12 septicaemias, 2 chest infections, 7 osteomyelitis or septic arthritis, and 15 were immunosuppressed patients with infected Hickman line site infections. The cure rate of the 85 evaluable episodes was 90% (76 cured). Teicoplanin was well tolerated intravenously and intramuscularly. Adverse reactions occurred in five patients. One patient suffered high tone hearing loss, two patients suffered transient rash, one developed a drug fever and one patient who had concomitant gentamicin developed vestibular damage. It is concluded that teicoplanin is a relatively safe and effacacious treatment for Gram-positive infection.

Anti-Bacterial Agents

Ciprofloxacin and co-trimoxazole in urinary tract infection.

Seventy-five hospital inpatients with bacteriologically confirmed urinary tract infections were allocated to treatment with ciprofloxacin 100 mg, ciprofloxacin 250 mg or co-trimoxazole 960 mg, all given orally twice a day for five days. The patients were generally elderly, with many complicating factors including indwelling catheters; 24% of the infections were caused by Pseudomonas aeruginosa. The cure rates at 28 days were 94%, 88% and 87%, respectively. Side effects were few and minor. Ciprofloxacin appears to be an effective and safe orally-administrable treatment even for complicated urinary tract infection.

Adult

Course organizers in general practice.

In August/September 1984 a survey of the 267 course organizers in post in England and Wales was carried out. Eighty-two per cent replied to a questionnaire asking for details about their work and personal status. All 16 regions in England and Wales completed a questionnaire about levels of staffing and remuneration of those involved in general practice postgraduate education. The results show that there are considerable variations between regions in the role and responsibilities of course organizers, in their training, and in the facilities that are provided for them. The majority of course organizers reported a workload greater than the number of sessions for which they were remunerated. The effects of these factors on recruitment, tenure of post, and job satisfaction are discussed. Recommendations are made for improving the situation, including the removal of course organizer pay from the scale of trainers' pay, so that there can be flexibility in the number of sessions which can be held, improvement in training and certain facilities, and the implementation of national and local job descriptions.

Adult

Comparative in vitro studies with 4-quinolone antimicrobials.

The minimal inhibitory concentrations (MICs) of nalidixic acid, pipemidic acid, cinoxacin, oxolinic acid, flumequine, pefloxacin, acrosoxacin, amifloxacin, norfloxacin, enoxacin, ofloxacin and ciprofloxacin were determined for a range of clinical isolates. MICs were determined using an agar dilution technique in Mueller-Hinton agar supplemented with 10% lysed horse blood. The inoculum used was approximately 10(4) colony forming units, contained in 10 microliters Mueller-Hinton broth, which was applied to the agar plates using a multipoint inoculator. Following inoculation, plates were incubated in conditions appropriate for the organisms under investigation. The MIC of each antimicrobial for each isolate examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentrations required to inhibit the growth of 50% (MIC50) and 90% (MIC90) of the organisms examined were also determined. All of the more recently synthesised 4-quinolones showed considerably greater activity than the parent compounds, nalidixic acid, pipemidic acid and cinoxacin, against the range of organisms used in this study. Ciprofloxacin and ofloxacin were the two most active of the 4-quinolones examined.

4-Quinolones

Glaucoma assessment by microcomputer.

An automated system for comprehensively monitoring glaucoma patients is described. This economic and practical microcomputer data system has been designed to be thoroughly 'clinician oriented' through the collaborative efforts of ophthalmological and computer specialists. It incorporates novel and efficient methods for transferring both automated and manually recorded perimetry data into analysable digital form. The system is inexpensive, simple to use, maintains safe records, allows thorough analysis of patient data, and can considerably reduce the administrative load on ophthalmological clinics.

Computers