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Biomedical subjects

E M Scott

Publications and source records attributed to E M Scott.

At least 73 records · Page 4Linked to original sources

Development of resistance to ciprofloxacin in nutrient-rich and nutrient-limited growth conditions in vitro by Pseudomonas aeruginosa isolates from patients with cystic fibrosis.

Five serial exposures of mucoid Pseudomonas aeruginosa from patients with cystic fibrosis to subinhibitory concentrations of ciprofloxacin resulted in stepwise increases in the MIC, with a mean proportional increase of 10. MICs were significantly lower in an iron-limited chemically defined medium than in Iso-Sensitest broth. The mucoid phenotype was maintained in chemically defined medium. Acquired resistance was retained either partially or completely in 85% of the isolates following 10 transfers in drug-free media. In cases in which susceptibility was regained, an increase in the MIC was observed on one further exposure to ciprofloxacin.

Cells, Cultured↗

Genetic polymorphisms in southwest Alaskan Eskimos.

Allele frequencies of 28 genetic loci were determined in subsets (n ranged from 52 to 698) of a sample of Yupik-speaking Eskimos from southwestern Alaska. Five loci were monomorphic (Kell Kp (b+), ADA1, AK1, HBA, and PGDA). At the other loci, the most frequent alleles were AB00 (0.580), Fya (0.960), Jkb (0.513), Ms (0.333), CDe (0.591), ACPA (0.566), ESD1 (0.890), GLO2 (0.736), GPT1 (0.653), Hp2 (0.654), PGM1 (0.836), PGP1 (0.972), and UMPK1 (0.873). The most frequent immunoglobulin allotype Gm(1;21) occurred with a frequency of 0.829. The HLA alleles that occurred with highest frequencies were A24 (0.626), Bw48 (0.184), Cw3 (0.404), and DR4 (0.329). The average heterozygosity at all loci was 0.423. Based on the presence of the European allotype, Gm3;23;5,11,13, the proportion of European admixture in the Eskimo population was estimated to be 2.1%.

Alaska↗

Comparative studies of catalase and superoxide dismutase activity within salmon fish erythrocytes.

1. Superoxide dismutase isolated from erythrocytes of several species of salmon and the rainbow trout exhibited single electrophoretic bands of activity which migrated anodally similar to the human erythrocyte enzyme; two discrete bands were observed for the coho salmon. 2. No polymorphism was observed for 30 samples from sockeye salmon and six samples from king salmon. Only one sample of rainbow trout (one of 12) exhibited an electrophoretic mobility difference. 3. Catalase migration on starch-gel resembled the human enzyme's electrophoretic mobility for all salmon species and rainbow trout. Catalase activity of the sockeye salmon (2929 +/- 895 mumol min-1 gHb-1) was determined to be lower than human catalase activity. 4. All samples differed from the human enzymes in that they required the presence of a detergent, Triton X-100, for solubilization.

Animals↗

The increase in plasma and saliva cortisol levels in pregnancy is not due to the increase in corticosteroid-binding globulin levels.

Total and free cortisol levels are significantly elevated in pregnancy, but the reasons for this are not clear. The relationships between the diurnal variation in saliva (free) cortisol and baseline levels of total cortisol, corticosterone-binding globulin (CBG), progesterone, and estrogens were studied in several groups of women (normal nonpregnant, taking a combined oral contraceptive pill, after superovulation therapy, during early and late pregnancy, and postpartum). Saliva cortisol levels were significantly elevated in late pregnancy throughout the day, with preservation of diurnal variation. Total cortisol and CBG levels were also significantly raised in pregnancy, but total cortisol levels were normal in women taking a combined oral contraceptive pill in spite of significantly elevated CBG. There was no relationship between saliva cortisol and progesterone levels, and it is unlikely that the increase in cortisol is due to displacement of cortisol from CBG by progesterone. Cortisol levels fell slowly postpartum over several days, making it improbable that the increase in cortisol is solely due to elevated CRH levels. It appears that increased free and total cortisol levels in pregnancy are related to resetting of the sensitivity of the hypothalamic-pituitary-adrenal axis and not merely to raised CBG, progesterone, or CRH levels.

Adult↗

Serial adrenal ultrasonography in normal neonates.

Six serial ultrasound scans were performed on each of 12 healthy term babies on days 1, 3, 5, 11, 21, and 42 of extrauterine life in order to determine normal neonatal values for various adrenal parameters. Measurements were made of transverse and anteroposterior diameters, of circumference and area in the transverse plane, and of longitudinal length of the adrenals and kidneys. There was a significant decrease in all adrenal parameters of 22%, 25%, 25%, 44%, and 34%, respectively, between days 1 and 5 (p less than .002) and of 46%, 39%, 46%, 67%, and 55%, respectively, between days 1 and 42 (p less than .00005), whereas the kidneys increased in size over the same period.

Adrenal Glands↗

A phase I clinical trial of recombinant interleukin 2 following high dose chemo-radiotherapy for haematological malignancy: applicability to the elimination of minimal residual disease.

Biological response modifiers such as interleukin 2 (IL2) may be most effective in the setting of minimal residual disease. In a phase I-II clinical trial, IL2 was administered to 10 patients in remission of acute myeloid leukaemia and three with multiple myeloma 1-4 weeks after treatment with ablative chemotherapy or chemotherapy and autologous bone marrow transplantation. The aim was to assess the capacity of these patients to tolerate IL2 after intensive therapy and to determine whether regenerating lymphocytes were capable of responding to IL2 with the generation of anti-leukaemic effector cells. Toxicity was severe in two patients treated with escalating doses of IL2 and 19 subsequent infusions administered to 11 patients on a fixed dose schedule for periods of 3-5 days were well tolerated. Major toxicity was confined to hypotension (two courses) which responded rapidly to treatment cessation. No patients required intensive care unit support. IL2 infusions produced no significant adverse effects on marrow regeneration; while there were transient falls in platelet counts there were no episodes of clinical bleeding and neutrophil counts increased from a mean of 1.1 pre-infusion to 2.5 x 10(9)l-1 during the infusion (P = 0.004). A significant biochemical abnormality was hypokalaemia which responded rapidly to correction. Cells with activity against leukaemic progenitor cells appeared in peripheral blood within 48 h of beginning treatment. We conclude that IL2 may be used in minimal residual haematological malignancy, and by producing anti-neoplastic effector cells has the potential, as yet unproven, to prolong disease-free survival of patients entering remission.

Adolescent↗

Hypnosis: emotions for the tin man (the schizoid personality).

Insight psychotherapy had been ineffective in helping a schizoid patient experience affect. He remained cold, aloof, and without overt expression of affect. When hypnosis was utilized, the patient overtly demonstrated affect. Hence the title for the article--hypnosis was effective in changing the tin man into a person with emotions and feelings. A discussion indicates some possible variables associated with this phenomenon.

Adult↗

Clinical and pharmacokinetic aspects of ciprofloxacin in the treatment of acute exacerbations of pseudomonas infection in cystic fibrosis patients.

Twelve cystic fibrosis patients, aged over 18, who had developed an acute respiratory exacerbation and who had Pseudomonas species isolated from their sputum, were entered into a clinical trial involving ciprofloxacin. The dosage regimen was 100 mg iv followed by 500 mg twice daily orally if less than 40 kg in weight and 200 mg iv followed by 750 mg twice daily orally if greater than 40 kg. Ciprofloxacin was well tolerated with no major side effects, except in one patient who withdrew after onset of headaches and generalized aches and pains. Eleven of the 12 patients showed clinical improvement at the end of the treatment period as determined by weight gain, Shwachman Score, Chrispin Norman Score and pulmonary function tests. MICs of Pseudomonas species isolated from the sputum at the start of the trial were in the range 0.25-4 mg/l. During therapy, sensitivity of isolates decreased and did not return to starting levels at the end of a four week follow-up period. Pharmacokinetic parameters were similar to those reported for fasting healthy volunteers by other workers except for bioavailability which was reduced in the non-fasting patients.

Administration, Oral↗

Effect of ciprofloxacin in an in-vitro pharmacokinetic model against Pseudomonas aeruginosa isolated during cystic fibrosis lung infection.

An in-vitro pharmacokinetic model was used to simulate ciprofloxacin concentrations in serum observed in vivo following oral doses of 250, 500 and 750 mg, in a culture of Pseudomonas aeruginosa isolated from the sputum of a cystic fibrosis patient. In the 12 h interval following each dose, a period of bactericidal activity was observed, succeeded by bacteriostasis and subsequent bacterial regrowth. In all cases bacterial regrowth was first observed when the ciprofloxacin concentration in the culture flask of the dynamic model fell below the MIC. For the three doses investigated, the surviving bacteria at the end of each 12-h dosing interval showed an increase in MIC compared with that of the culture before ciprofloxacin exposure. The post-antibiotic effect of ciprofloxacin against P. aeruginosa was observed for 1-5 h, and was dose related.

Ciprofloxacin↗

Miconazole sorption to intravenous infusion sets.

The sorption of the antifungal drug miconazole onto the plastics of infusion bags and intravenous administration sets has been investigated. HPLC methodology was applied for the determination of miconazole concentrations. The results obtained indicate that the sorption of miconazole is low and is unlikely to result in significant loss of clinical efficacy.

Adsorption↗

The value of routine preoperative investigations.

In a prospective study of 400 patients admitted for elective surgery, the value of preoperative investigations in identifying the group at high risk of complications was assessed. In order to evaluate methods of reducing the number of investigations a preoperative questionnaire was used and patients were also grouped with regard to age and extent of surgery. Sixteen per cent of the results of the preoperative investigations showed some abnormality but only 0.013% caused a change in management. Abnormal results were significantly associated with complications (P less than 0.05). A positive (abnormal) questionnaire and increased age together defined a group more likely to have abnormal results (P less than 0.05) but age was a more specific indicator. The extent of surgery was not associated with abnormal results other than biochemistry results but was associated with complications (P less than 0.01) and with the need to repeat investigations postoperatively. It was concluded that a preoperative questionnaire might be useful in the assessment of day case patients, where a larger fraction would be expected to fall into the low risk group. A policy for routine preoperative investigation was drawn up. Full blood count should be performed in all patients over 40 years, ECG in all patients over 50 years and CXR and urea and electrolytes in patients over 60 years undergoing major surgery. Asymptomatic patients out with these categories do not require routine investigations.

Adolescent↗

Uridine monophosphate kinase and susceptibility to invasive Haemophilus influenzae type B disease.

A polymorphic genetic variant of the pyrimidine pathway enzyme, uridine monophosphate kinase-3 (UMPK-3), was positively associated with invasive Hib disease. All UMPK 3-3 homozygotes in this study were Hib cases, and we found that in cases and controls, there was no difference between UMPK phenotype and serum levels of total Hib antibody as measured by radioimmunoassay. This suggests that UMPK-3 may play a role in mediating the non-humoral immunity to Hib. However, unlike other enzyme variants in the nucleoside synthesis pathways which result in syndromes of severe immunodeficiency, this gene appears to confer a more subtle disease susceptibility. Thus, the UMPK-3 allele, although rare in Caucasians, is associated with an increased risk of invasive Hib infection in Alaskan Eskimos.

Alaska↗

Effect of miconazole and clotrimazole on K+ release and inhibition of ergosterol biosynthesis in Trichophyton mentagrophytes and related ultrastructural observations.

Measurement of K+ ions in extracellular fluids was used to provide evidence of direct membrane damage induced by miconazole and clotrimazole in Trichophyton mentagrophytes mycelium. K+ release from mycelium treated with high concentrations of drug was extensive, although leakage occurred more rapidly and to a greater extent with miconazole than with clotrimazole. Cells treated with fungicidal concentrations of drug were completely necrotic. The effect of miconazole was concentration dependent. A reduction in ergosterol levels was evident after 5 h treatment with miconazole. Further reduction in ergosterol concentration was demonstrated after 24 h with fungistatic concentrations of drug and was a concentration dependent effect. Fungistatic concentrations of miconazole also induced ultrastructural changes in mycelium, which were apparent within 5 h of treatment and became more pronounced after 24 h. Clotrimazole also reduced ergosterol levels and affected ultrastructure of mycelium. The plasma membrane in particular was affected by both these drugs.

Cell Membrane Permeability↗

An assessment of the fungicidal activity of antimicrobial agents used for hard-surface and skin disinfection.

Trichophyton mentagrophytes and Aspergillus niger conidia and Candida albicans blastospores were employed to assess the fungicidal activity of a range of antimicrobial agents used for hard-surface and skin disinfection in hospitals in the U.K. The antimicrobials were tested at in-use concentrations. The time taken to give greater than 99.99% kill was determined by estimating the number of survivors (cfu/ml) at a variety of time intervals after exposure of washed suspensions of spores to the disinfectants. At equivalent times the recovery in the broth was investigated. An alcoholic solution of chlorhexidine gluconate (0.02%) (Hibitane), iodine in Industrial Methylated Spirit (IMS) and a phenolic (0.36% phenols, Stericol) produced a 99.99% kill of all species within 2 min, alcoholic and aqueous solutions (10%) of povidone-iodine (Betadine) and hypochlorite (0.2%) required 10 min to give a 99.99% kill of all species tested. The preparations which contained cetrimide (Cetavlon), aqueous solutions of chlorhexidine gluconate (Hibitane) and combinations of these (Savloclens and Savlodil) were only slowly fungicidal, particularly against T. mentagrophytes spores, which was the most resistant of the three fungal species to disinfection.

Anti-Infective Agents, Local↗

Uridine monophosphate kinase 3: a genetic marker for susceptibility to Haemophilus influenzae type B disease.

Alaskan Eskimos have the highest known prevalence of invasive Haemophilus influenzae type b (Hib) disease, primarily meningitis, affecting 1-5% of all children in the first two years of life. In this population a polymorphic genetic variant of the pyrimidine pathway enzyme, uridine monophosphate kinase-3 (UMPK-3), was found to be positively associated with invasive Hib disease (relative risk 3.3) and a tendency towards a younger age at onset of illness. There was no difference in levels of naturally acquired Hib anticapsular antibody between persons with Hib disease and healthy controls in this population. This suggests that UMPK-3 may have a role in mediating non-humoral immunity to Hib. However, unlike other enzyme variants in the nucleoside synthesis pathways which result in syndromes of severe immunodeficiency, this gene appears to confer a more subtle disease susceptibility.

Age Factors↗