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Biomedical subjects

A Geddes

Publications and source records attributed to A Geddes.

15 recordsLinked to original sources

Transcription of essential cell division genes is linked to chromosome replication in Escherichia coli.

Cell division normally follows the completion of each round of chromosome replication in Escherichia coli. Transcription of the essential cell division genes clustered at the mra region is shown here to depend on continuing chromosomal DNA replication. After chromosome replication was blocked by either nalidixic acid treatment or thymine starvation, the transcription of these cell division genes was repressed significantly. This suggests a way in which cell division is controlled by chromosome replication.

Bacterial Proteins↗

Infection in the twenty-first century: predictions and postulates.

The late Paul Garrod, in whose honour this lecture is named, was 'the right man at the right time'. He seized the opportunities offered by the dawning of the chemotherapeutic era with vigour and enthusiasm and was a formidable link between the traditional laboratory-based bacteriologist and the more clinically orientated 'modern' medical microbiologist. Professor Garrod was a founder member of the British Society for Antimicrobial Chemotherapy and I had the privilege of meeting him on many occasions. He would have relished the many challenges facing today's microbiologists, infectious disease physicians and public health experts. These will have major implications for antimicrobial chemotherapy in the twenty-first century. The emergence and prevalence of infectious diseases, and the necessity for discovering therapies to treat them, are influenced by many factors. In this lecture I will discuss four which could have a major influence on infectious diseases in the twenty-first century-global warming, biological warfare/terrorism, the dissemination of infections, including those caused by resistant pathogens, by travellers and certain untreatable zoonotic diseases.

Animals↗

Levofloxacin in the empirical treatment of patients with suspected bacteraemia/sepsis: comparison with imipenem/cilastatin in an open, randomized trial.

An open, randomized, multinational, multicentre study was conducted to compare the efficacy, safety and tolerability of levofloxacin 500 mg twice daily with imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized adult patients with clinically suspected bacteraemia/ sepsis. Levofloxacin patients could change from iv to oral administration after a minimum of 48 h iv treatment if clinical signs and symptoms of sepsis had improved. The primary efficacy analysis was based on the clinical and bacteriological response at clinical endpoint. A total of 503 patients were randomized and 499 included in the intent-to-treat population. The per-protocol population comprised 287 patients with bacteriologically proven infection. Clinical cure rates at clinical endpoint in the intent-to-treat population and per-protocol population were 77% (184/239) and 89% (125/140), respectively, for levofloxacin and 68% (178/260) and 85% (125/147), respectively, for imipenem/cilastatin. At follow-up, the cure rates in the per-protocol population were 84% for levofloxacin and 69% for imipenem/cilastatin. The 95% confidence interval for both populations showed that levofloxacin was as effective as imipenem/cilastatin. A satisfactory bacteriological response was obtained in 87% (96/110) of levofloxacin patients and 84% (97/116) of imipenem/cilastatin patients at clinical endpoint. Adverse events possibly related to the study drug were reported in 74 (31%) levofloxacin patients and 79 (30%) imipenem/cilastatin patients. There were no clinically appreciable differences between the treatment groups. Levofloxacin 500 mg twice daily, either iv or as sequential iv/oral therapy, was as effective and well tolerated as imipenem/cilastatin 1 g iv three-times daily in the treatment of hospitalized patients with suspected bacteraemia/sepsis.

Adolescent↗

Immune responses of IL-5 transgenic mice to parasites and aeroallergens.

Eosinophils have long been thought to be effectors of immunity to helminths but have also been implicated in the pathogenesis of asthma. Patterns of cytokine production in the host may influence the pathogenesis of these diseases by regulating the activities of eosinophils and other components of the immune response. Mice which constitutively over-express IL-5 have profound and life-long eosinophilia in a restricted number of tissues. Although eosinophils from IL-5 transgenics are functionally competent for a number of parameters considered to be important in inflammation, untreated animals are overtly normal and free of disease. In addition, the responses of these animals when exposed to aeroallergens and helminths present a number of apparent paradoxes. Eosinophil accumulation in tissues adjacent to major airways is rapid and extensive in transgenics exposed to the aeroallergen, but even after treatment with antigen over many months these mice show no evidence of respiratory distress or pathology. Helminth-infected IL-5 transgenics and their non-transgenic littermates develop similar inflammatory responses at mucosal sites and are comparable for a number of T cell and antibody responses, but they differ considerably in their ability to clear some parasite species. The life-cycle of Nippostrongylus brasiliensis is significantly inhibited in IL-5 transgenics, but that of Toxocara canis is not. Our results also suggest that eosinophilia and/or over-expression of IL-5 may actually impair host resistance to Schistosoma mansoni and Trichinella spiralis. The pathogenesis of diseases in which eosinophils are involved may therefore be more complex than previously thought.

Allergens↗

Comparative efficacy of sparfloxacin versus ciprofloxacin in the treatment of complicated urinary tract infection.

A total of 686 adult patients with complicated urinary tract infections were enrolled in a double-blind, randomised, multicentre study to compare sparfloxacin (200 mg loading dose on day 1 followed by 100 mg daily) with ciprofloxacin (500 mg orally twice daily) for 10 to 14 days. Urinary tract infection was defined as pyuria and bacteriuria (cfu > or = 10(5)/mL). Evaluations were performed at four time-points. The clinical efficacy of the two antibacterial agents was equivalent at the end of treatment: clinical cure in 88.6% of the intent-to-treat population and 87.3% in the evaluable population treated with sparfloxacin compared to 85.4% and 84.8% of the intent-to-treat and evaluable populations, respectively, treated with ciprofloxacin. The clinical results were also equivalent at follow-up. The bacteriological efficacy of the two agents was not equivalent. At the end of treatment, bacteriological cure was observed in 72.6% of the intent-to-treat and 72.1% of the evaluable populations treated with sparfloxacin and in 81.4% and 80.8% of the intent-to-treat and evaluable populations, respectively, treated with ciprofloxacin. The difference was primarily because of a higher number of persisting pathogens, which included Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and enterococci, which exhibited moderate susceptibility to sparfloxacin. Tolerability was similar in the two treatment groups.

Adolescent↗

Percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is now the technique of choice for patients requiring long-term enteral feeding. It is a good method for feeding patients with neurological dysphagia and can safely be kept in situ for long periods. PEG feeding requires a multidisciplinary approach, involving doctors, nurses, pharmacists, speech therapists, dieticians and carers. The insertion of a PEG, which requires two operators and two endoscopy nurses, is described in full. Feeding can commence after a few hours. Various types of feed and feed-ing patterns are described and their relative merits discussed. Although psychological problems may occur following PEG insertion, the procedure is usually well accepted by patients.

Contraindications↗

Cytotoxicity of ketoconazole in malignant cell lines.

The cytotoxic effects of ketoconazole, an antifungal agent known to have some activity against human prostate cancer, adrenal cancer, and male metastatic breast cancer, were evaluated using colony-growth and clonogenic assays in eight malignant cell lines. The cytotoxicity of ketoconazole showed a dose- and time-dependent pattern, with the following concentrations inhibiting 90% of the growing colonies (IC90): MCF 7 (human breast cancer) 7.25 micrograms/ml, T 47 D (human breast cancer) 9.0 micrograms/ml, MiaPaCa (human pancreatic carcinoma) 10.0 micrograms/ml, COLO 357 (human pancreatic carcinoma), 9.5 micrograms/ml, HCT 8 (human colonic adenocarcinoma) 27.1 micrograms/ml, DU 145 (human prostatic cancer) 40.0 micrograms/ml, AR 42 J (rat pancreatic carcinoma) 9.0 micrograms/ml, and L1210 (murine leukemia) 8.6 micrograms/ml. Since a concentration of 10 micrograms/ml can be achieved in humans, the use of ketoconazole in human malignancies might be worthy of clinical evaluation.

Animals↗

Induction of intracisternal type A particles by 5-bromo-2'-deoxyuridine in rat hepatoma cells.

Electron microscopic examination of hepatoma tissue culture (HTC) cells revealed low numbers of intracisternal type A particles (IAP) and type C viruses. Exposure of HTC cells to either 10(-4) or 10(-5) M5-bromo-2'-deoxyuridine (BUdR) caused a more than 50-fold increase in the number of IAP observed with the electron microscope. The number of IAP increased after only 2 days of growth in 10(-5) M BUdR, whereas 3 days of growth in 10(-4) m BUdR were necessary to observe an increase. A 2-day pulse of 10(-4) M BUdR was also sufficient to cause the increase in type A particles, provided the cells were continued in culture for another 2 days. Unlike many other cell lines, HTC cells treated with BUdR did not show an increase in type C viruses. This conclusion was based on the observations that BUdR treatment caused no detectable increase in extracellular particulate viral reverse transcriptase or in viral RNA complementary to a DNA probe made to a rat endogenous type C virus (RaLV).

Animals↗

The team approach to percutaneous endoscopic gastrostomy feeding.

The importance of early recognition and treatment of patients who are at risk of developing malnutrition is becoming increasingly recognised. Percutaneous endoscopic gastrostomy has become increasingly popular as a method of feeding, since its description in 1980, because of its ease of insertion and low morbidity and mortality. Its success, however, depends upon the use of a multidisciplinary approach.

Administration, Cutaneous↗