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Biomedical subjects

J Easterbrook

Publications and source records attributed to J Easterbrook.

7 recordsLinked to original sources

The unilateral swollen lower limb: etiology, investigation, and management.

The swollen lower limb, a common finding in routine clinical practice, is clinically challenging. The cause underlying this problem is often multifactorial, and its management may involve different specialties. It is important, though difficult, to avoid unnecessary and expensive investigations. The aim of this article is to provide an overview of the management of this problem by addressing the common causes, methods of assessment, diagnosis, and therapeutic options.

Journal Article↗

A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation.

Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.

Animals↗

Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes.

We studied the effects of acetonitrile, dimethyl sulfoxide (DMSO), and methanol (MeOH) in human hepatocytes on cytochrome P450 (CYP) and phase II conjugation activities: phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), testosterone 6beta-hydroxylation (CYP3A4), and umbelliferone glucuronidation and sulfation. The solvents were evaluated at concentrations (v/v) of 0.1, 1, and 2%. Previously cryopreserved human hepatocytes pooled from multiple donors were used as suspension cultures in this study. DMSO was found to inhibit CYP2C9 and CYP2C19, CYP2E1, and CYP3A4 in a concentration-dependent manner. At 2% DMSO, the activities for the four isoforms were approximately 40% (CYP2C9), 23% (CYP2C19), and 11% (CYP2E1) of that observed for 0.1% acetonitrile and 45% (CYP3A4) of that observed for 1% acetonitrile. No apparent inhibitory effects were observed for the other activities evaluated. Methanol was found to inhibit CYP2C9 and CYP2E1 activities, but to a lesser extent than DMSO. Acetonitrile had no apparent effects on any of the on any of the activities evaluated. These findings should be considered when choosing an organic solvent for metabolism studies with human hepatocytes.

Acetonitriles↗

Melnick-Needles syndrome. Four new cases.

Melnick-Needles syndrome is a rare connective tissue disorder producing somatic abnormalities with characteristic radiographic features. There are less than 35 documented cases reported to date. We present four new cases of Melnick-Needles Syndrome, one of which is the first reported Asian-ancestry patient. Two girls are daughters of one of Needle's original patients from family #2. Two others, from unrelated non-affected families, probably represent new mutations. All have characteristic radiographic features of the disorder.

Adolescent↗

The neuroradiology of visual disturbances.

The neuroradiology of visual deficits has advanced dramatically in recent years. Plain film evaluation of the orbit and face remains useful in the emergency room for the evaluation of trauma. High-resolution coronal CT remains the method of choice in the assessment of serious injury to the orbit and in cases of penetrating metallic foreign body. The contrast-enhanced orbital CT provides useful information in cases of tumor and infection and when the bones of the face or skull are involved. MRI has largely replaced CT in the search for brain infarct, brain tumor, and cerebral inflammatory and demyelinating processes. MRI is the study of choice in all cases of sellar and parasellar disease. It offers high-resolution images in any plane. GTPA enhancement has provided additional information from MRI without significant risk. The final selection of an imaging modality should be based upon the clinical presentation and any physical limitations of the patient.

Brain Neoplasms↗

Disablement and eye contact.

This study investigated the effect of height level and wheelchair presence on eye contact and interaction. Presence of a wheelchair increased eye contact to a standing colleague, possibly due to the wheelchair-confined individuals' perceived dependence on others.

Adult↗