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Biomedical subjects

M Hall

Publications and source records attributed to M Hall.

At least 361 records · Page 20Linked to original sources
PubMedDate not supplied

Identification of enzymes involved in phase I metabolism of ciclesonide by human liver microsomes.

Ciclesonide, a novel inhaled corticosteroid, is currently being developed for the treatment of asthma. Here, the enzymes catalysing the human hepatic metabolism of ciclesonide were investigated. When incubated with human liver microsomes (HLM), [14C]ciclesonide was first metabolised to the active metabolite M1 (des-isobutyryl-ciclesonide, des-CIC) and to at least two additional metabolites, M2 and M3. M3 comprises a 'family' of structurally similar metabolites that are inactive. 16-Hydroxyprednisolone was also formed in microsomal incubations of [14C]des-CIC, but at approximately one-tenth the amount of both M2 and M3. bis-p-Nitrophenylphosphate and SKF 525-A respectively inhibited des-CIC formation from [14C]ciclesonide by 82% and 49% and M2/M3 formation by 82-84% and 87-89%. Regression analysis showed significant negative correlations (r = -0.96, -0.79 and -0.71, respectively) of M2 formation with CYP3A4/5, CYP2B6 and CYP2C8 activities; M3 formation significantly correlated with CYP4A9/11 (r = 0.47). Troleandomycin and diethyldithiocarbamate inhibited M2 and M3 formation by 85% and 45%, respectively. Sulphaphenazole and quinidine had no inhibitory effects. CYP3A4 Supersomes catalysed notable formation of both M2 and M3 from [14C]des-CIC; CYP2C8 and CYP2D6, but not CYP4A11 formed smaller amounts. It is concluded that the human hepatic metabolism of ciclesonide is primarily catalysed by one or more esterases and, subsequently, by CYP3A4.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis.

In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis.

Adolescent↗
PubMedDate not supplied

False-positive postmortem EMIT drugs-of-abuse assay due to lactate dehydrogenase and lactate in urine.

Three cases of multiple false-positive drug tests are described. Postmortem urine specimens were screened using the enzyme-multiplied immunoassay technique. All patients had proteinuria and lactic aciduria. These false-positive reactions were due to the presence of lactate dehydrogenase (LDH), lactic acid, and protein. This finding was confirmed by creating a multiple false-positive sample with a solution of LDH and lactate in 5% bovine serum albumin at pH 6.

Adult↗
PubMedDate not supplied

Control and intrusive memories as possible determinants of chronic stress.

Amidst confusion about the nature and usefulness of the stress construct and distinctions between acute and chronic stress, research has begun to identify mechanisms by which stress affects health and by which stress can persist beyond the physical presence of the stressor. In addition, research has begun to identify reasons for selective vulnerability to chronic stress. One of the possible reasons for chronic stress following traumatic events is the disorganizing effect of loss of control and violation of expectations for regulating aspects of one's life normally under control. Data from a longitudinal study of chronic stress at Three Mile Island in the wake of the nuclear accident there suggest that loss of control and frequent experience of intrusive memories about the accident and its aftermath were related to persistent stress responding several years after the accident. The relationships between stress responding and conditioning and consolidation of stressful memories are considered as a basis for persistent intrusive memories and chronic stress.

Adaptation, Psychological↗
PubMedDate not supplied

Sleep as a mediator of the stress-immune relationship.

OBJECTIVE: To evaluate the role of sleep in the relationship of intrusive thoughts/avoidance behaviors to natural killer cell (NKC) number and function. METHOD: Twenty-nine individuals seeking treatment for bereavement-related depression were studied in the sleep laboratory. Background and clinical variables, including the Impact of Event Scale (IES) and the Hamilton Rating Scale for Depression (HRSD), were administered during the week preceding a 3-night sleep study. Blood samples were collected upon awakening after the second or third night of sleep. RESULTS: Greater frequency of intrusive thoughts and avoidance behaviors was associated with more time spent awake during the first non-rapid eye movement period (NREM-1) and lower NKC number (p values < .01). Greater time spent awake during NREM-1 was associated with lower NKC numbers (p < .05). Regression analyses revealed that the significant relationship between symptoms of intrusion/avoidance and NKC number was no longer significant when time spent awake during NREM-1 was entered into the regression equation. Time spent awake during NREM-1 accounted for 12% of the variance in NKC number (p < .05), whereas intrusion/avoidance accounted for 7% of the variance in NKC number (NS). CONCLUSIONS: These results suggest that EEG-assessed sleep may be a significant correlate of the stress-immune relationship.

Adult↗
PubMedDate not supplied

Symptoms of stress and depression as correlates of sleep in primary insomnia.

OBJECTIVE: Previous studies have not evaluated the clinical correlates of the electroencephalographic spectral profile in patients with insomnia. In the preliminary study described here, we evaluated the extent to which symptoms of stress and depression are associated with subjective sleep complaints and quantitative measures of sleep in individuals with chronic insomnia. METHODS: Subjects were 14 healthy adults who met criteria for primary insomnia as specified in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Measures of stress, depression, and subjective sleep quality were collected before subjects participated in a two-night laboratory sleep series. We hypothesized that elevated symptoms of stress and depression would be associated with subjective sleep complaints and electroencephalographic evidence of hyperarousal during sleep. Hyperarousal during sleep was defined as decreases in delta power and elevations in alpha and beta power throughout non-rapid eye movement sleep, and symptoms of stress were defined as the tendency to experience stress-related intrusive thoughts and the interaction between intrusion tendency and the number of recent stressful events (subjective stress burden). RESULTS: A stronger tendency to experience stress-related intrusive thoughts was associated with greater sleep complaints and a trend toward higher beta power, whereas increases in subjective stress burden were associated with decreases in delta power. In addition, elevations in subclinical symptoms of depression were associated with greater sleep complaints and elevations in alpha power. CONCLUSIONS: Observed relationships among symptoms of stress, depression, subjective sleep complaints, and electroencephalographic power may be relevant to the discrepancy between subjective and objective measures of sleep in patients with insomnia and may be more broadly applicable to sleep complaints in association with stressful life events and major depression.

Adult↗
PubMedDate not supplied

Acute ketotifen overdosage. A review of present clinical experience.

Ketotifen (Zaditen) is a widely used prophylactic antiasthmatic drug with pronounced antianaphylactic properties and a specific H1-antihistaminic effect. This article summarises the available information on acute overdosage of this drug, which was reported in 13 adults and 8 children. The symptoms of acute overdosage observed with ketotifen are similar to those described for antihistaminic agents. However, it would appear that the acute toxicity of ketotifen is rather low, since no serious effects have been reported either in children or in adults after the intake of up to 20mg of ketotifen, which is 10 times the recommended dose. No lethal outcome of acute overdosage has been described in association with this drug. Ketotifen seems to be better tolerated in children than in adults. Based on present clinical experience, management of acute overdosage includes gastric lavage within 2 to 4h after ingestion or activated charcoal after this period. Symptomatic treatment is indicated if arrhythmias, hypotension or seizures develop, and the patient should be kept under surveillance for at least 6 to 8h.

Adult↗
PubMedDate not supplied

Sensitivity of cortical transit and furosemide response in the diagnosis of renal obstruction. An experimental model.

Several radionuclide parameters are routinely used for the diagnosis of renal obstruction. In order to evaluate the sensitivity of those parameters, an experimental model of partial ureteral obstruction in rats was used. Neither the cortical transit time, nor the response to furosemide could serve to discriminate between obstructive and nonobstructive kidneys. These parameters were, however, more or less related to the degree of impairment of the single kidney glomerular filtration rate and should probably be considered as functional parameters reflecting the grade of the obstructive phenomenon.

Animals↗