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Biomedical subjects

N M Brown

Publications and source records attributed to N M Brown.

At least 55 records · Page 3Linked to original sources

Absorption of oral ofloxacin after cytotoxic chemotherapy for haematological malignancy.

Ten patients with newly diagnosed haematological malignancy were given ofloxacin, 400 mg daily orally, for antibacterial prophylaxis during neutropenia. Before cytotoxic chemotherapy was given, and on three occasions between days 2-3, 5-7 and 8-10 afterwards, blood samples were taken before and 1, 2, 3, 4, 6 and 10 h after administration of ofloxacin. Serum ofloxacin concentrations were measured by HPLC. Mean (range) pharmacokinetic parameters before chemotherapy were: Cmax, 6.1 (2.7-9.1) mg/L; AUC0-2, 7.5 (1.9-11.6) mg.h/L. On days 2-3 post-chemotherapy the values were reduced to: Cmax, 5.0 (3.6-7.3) mg/L; AUC0-2, 5.8 (1.9-7.8) mg.h/L. On days 5-7 the values were: Cmax, 6.1 (4.0-10.4) mg/L; AUC0-2, 8.5 (0.8-16.8) mg.h/L, and by days 8-10 the values were: Cmax, 6.4 (3.3-12.5) mg/L; AUC0-2, 8.6 (0.8-23.1) mg.h/L. There was a statistically significant difference between Cmax pre- and Cmax two to three days post-chemotherapy (paired t-test, P = 0.05). These changes are similar to those previously reported with ciprofloxacin but less marked.

Adolescent↗

Mycobacterial contamination of fibreoptic bronchoscopes.

Contamination of bronchoalveolar lavage specimens by environmental mycobacteria in hospital water supplies may lead to diagnostic confusion, particularly in immunocompromised patients. Mycobacteria may become concentrated in the tubing of bronchoscope disinfecting machines. It is very difficult to eradicate these organisms once contamination has occurred.

Adult↗

Clonal expansion of cells with trisomy of chromosomes 12 and X in an EBV-transformed lymphoblastoid cell line and establishment of a tumorigenic monoclonal cell line (48,XX,+X,+12).

Clonal expansion of cells with a certain abnormal chromosome constitution has been demonstrated in EBV-transformed lymphoblastoid cell lines, and a new monoclonal tumorigenic cell line (48,XX,+X,+12) has been established. Based on these data and our previous hypothesis that predisposition to tumor development could be associated with inherited susceptibility of certain chromosomes and chromosome regions to breakage, we emphasize that cytogenetic analysis of immortalized cell populations established from normal individuals and cancer patients might be of great importance for predicting development of different primary and secondary malignancies.

Animals↗

Acremonium infection in a neutropenic patient.

Acremonium species (previously Cephalosporium) are saprophytic moulds of low pathogenicity commonly found in the environment. We report a case of repeated acremonium fungaemia in a neutropenic patient, probably associated with a Hickman line. Fungaemia was accompanied by fever and a papular skin rash, both of which appeared to resolve when the neutrophil count recovered without antifungal chemotherapy, only to return when the patient next became neutropenic.

Acremonium↗

A preliminary scanning tunnelling microscopy study of the surface-organised structures of gramicidin S hydrochloride on highly oriented pyrolytic graphite.

For an initial study of potentially surface-structural self-organising systems of biological significance by scanning tunnelling microscopy (STM), gramicidin S, a pseudocentrosymmetric cyclodecapeptide with antibiotic properties, was chosen as prototype, recognising its structure as having both intramolecular and intermolecular hydrogen-bond forming propensity. The surface-organised structures, based on gramicidin S hydrochloride deposited on a highly oriented pyrolytic graphite (HOPG) substrate, have been observed by STM in air under ambient conditions. These are characterised in the main by rectangular or rectangle-like structural elements identified with the individual gramicidin S hydrochloride molecules. Two kinds of arrangements of gramicidin S hydrochloride in a two-dimensional array are found, i.e., as a centred rectangular lattice and a primitive rectangular lattice. The STM topographical arrays and the molecular dimensions obtained are in good quantitative agreement with the corresponding X-ray crystallographic data. The differences between the STM results, the theoretical models, and the X-ray crystallographic data are attributed to the intermolecular interactions present in the three-dimensional gramicidin S crystal but absent in the lower dimensional arrays and to the environments in which a gramicidin S hydrochloride molecule finds itself during deposition and drying on the HOPG substrate.

Amino Acid Sequence↗

The value of C-reactive protein in the diagnosis of intestinal perforation in typhoid fever.

Serum C-reactive protein concentrations were measured in 28 Nigerian patients with typhoid fever on presentation at hospital and at intervals thereafter. Five of the 28 (18%) were subsequently diagnosed as suffering from ileal perforation. These patients had concentrations of C-reactive protein during the first 24 h of admission which were significantly higher (mean = 229 mg/L) than those without perforation (mean = 91 mg/L). C-reactive protein may have a role in the prediction of early diagnosis of perforation in patients with typhoid fever.

C-Reactive Protein↗

Septicaemia due to Neisseria lactamica--initial confusion with Neisseria meningitidis.

Neisseria lactamica, isolated from a baby with septicaemia, was at first thought to be Neisseria meningitidis, possibly acquired in hospital. Extensive investigation of contacts was made until the O-nitrophenyl-D-galactopyranoside reaction proved positive. Distinction between the two species, easily made in this way, is important both in individual patients and in population surveys.

Bacterial Infections↗

Prototype quantitative assay for fibrinogen/fibrin degradation products. Clinical evaluation.

A new quantitative assay for fibrinogen/fibrin degradation products (FDPs) was clinically evaluated in 123 tertiary-care patients for whom the standard semiquantitative FDP assay had previously been ordered. On the basis of a comprehensive chart review, 24 patients were categorized as having disseminated intravascular coagulation (DIC), 84 were considered not to have had DIC, ten had fibrinolysis (nine of ten streptokinase induced), and five had a complicated coagulopathy whose exact nature could not be determined. The quantitative and semiquantitative FDP values were significantly correlated. However, the FDP level indicative of DIC was lower by the quantitative assay than by the semiquantitative assay, approximately 18 mg/L vs 40 mg/L, respectively. The advantages of the quantitative over the semiquantitative assay included improved precision and ability to closely monitor changes in the severity of the coagulopathy.

Disseminated Intravascular Coagulation↗

Review of investigations of dichloromethane metabolism and subchronic oral toxicity as the basis for the design of chronic oral studies in rats and mice.

In preparation for the design and performance of chronic toxicity and carcinogenicity studies in rats and mice on dichloromethane (methylene chloride; DCM), biochemical, mutagenicity, short-term, metabolic and subchronic feeding studies were carried out. These studies established that it was feasible to present DCM to rodents at adequate levels in drinking-water. Saturation of metabolic pathways was demonstrated in both rats and mice at oral doses of approximately 100 mg/kg. The lowest toxic effect levels after 90 days of treatment were found to be approximately 190 and 580 mg/kg for rats and mice, respectively. Dose, vehicle and the exposure regimen were found to affect DCM challenge to target tissues and its metabolism to CO and CO2.

Absorption↗

A two-year drinking-water study of dichloromethane in rodents. I. Rats.

In order to evaluate its toxicity and carcinogenic potential, dichloromethane (DCM) at levels of 0, 0, 5, 50, 125 and 250 mg/kg body weight/day was administered in deionized water to a total of 500 Fischer 344 rats of each sex for 104 wk. An additional group received a level of 250 mg/kg body weight/day for 78 wk followed by a 26-wk recovery period during which only deionized water was presented. Kills were performed at 26-wk intervals. Statistically significant effects on body weight, water consumption and food consumption were observed at the two highest dose levels. Minimal effects were noted on the haematological and serum chemistry parameters monitored. Treatment-related hepatic changes were observed histomorphologically in both sexes after 78 wk of treatment. These changes consisted of an increased incidence of foci/areas of cellular alteration and of fatty change at all dose levels except the lowest. A decrease in the severity of fatty change was observed in the recovery group, but no difference was noted in the incidence of cellular alteration. An increased incidence of hepatic tumours noted in females treated at 50 and 250 mg/kg/day was within the range of historical control incidences. In view of an unusually low incidence of similar tumours in the concurrent control groups and the absence of an increased incidence of hepatic tumours in the group treated at 125 mg/kg/day, the effect seen at 50 and 250 mg/kg/day was not considered to be attributable to DCM treatment. Under the experimental conditions of this study, there was a no-observable-effect level of 5 mg/kg/day in both males and females.

Administration, Oral↗

A two-year drinking-water study of dichloromethane in rodents. II. Mice.

To investigate its carcinogenic potential, dichloromethane (DCM) was administered at levels of 0, 0, 60, 125, 185 and 250 mg/kg body weight/day to a total of 1000 B6C3F1 mice in deionized drinking-water for 104 wk. The high-dose male and female mice showed a transitory increase in mean leucocyte counts. Treatment-related toxic changes were noted in both male and female livers at the highest dose. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose-related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no-observable-effect level (NOEL) for DCM of 185 mg/kg body weight/day in both sexes.

Administration, Oral↗

Immune response of Lewis rats to peptide C1 (residues 68-88) of guinea pig and rat myelin basic proteins.

Peptide C1 (residues 68-88) from GP and rat BP differ by a single amino acid interchange at residue 79. This residue is serine in GP C1 and threonine in rat C1. GP C1 was encephalitogenic in Le rats at doses as low as 15 ng. Rat C1 was encephalitogenic at doses of 1,500 ng or greater. LNC from rats challenged with 25 X 10(-4) micronmol of GP C1 and 250 X 10(-4) micronmol of rat C1 showed a proliferative response in vitro to both peptides, but in each instance the magnitude of the response was greater to the GP peptide. GP C1 also induced higher levels of circulating antibodies at 25 X 10(-4) micronmol, but the specificity of antibodies produced by the two peptides was the same. These results have been interpreted as indicating that the presence of serine at position 79 in GP C1 results in the stimulation of greater numbers of T cells involved in (a) the induction of EAE, (b) the in vitro proliferative response and (c) helper function in antibody production.

Amino Acid Sequence↗