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Biomedical subjects

J Adams

Publications and source records attributed to J Adams.

At least 271 records · Page 15Linked to original sources

BIRM 270: a novel inhibitor of arachidonate release that blocks leukotriene B4 and platelet-activating factor biosynthesis in human neutrophils.

(S)-N-[2-Cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (BIRM 270) was identified as a potent and enantiomerically selective inhibitor of calcium ionophore A23187-stimulated leukotriene B4 biosynthesis in human neutrophils. The (S)- and (R)-enantiomers exhibited IC50 values of 1 nM and 40 nM, respectively. BIRM 270 did not inhibit 5-lipoxygenase activity in a cell-free assay. In addition, the compound did not interfere with the conversion of exogenous 5-lipoxygenase substrate (15S)-hydroperoxyeicosatetraenoic acid to (5S, 15S)-dihydroxyeicosatetraenoic acid in intact, ionophore-stimulated neutrophils. Under the same experimental conditions, BIRM 270 inhibited the production of 5-lipoxygenase products from endogenous substrate, suggesting that the compound affected arachidonate availability rather than metabolism. Consistent with this concept, the inhibition of leukotriene B4 biosynthesis by BIRM 270 was overcome by the addition of exogenous arachidonic acid to the leukocyte preparation. Direct measurement of free arachidonate by gas chromatography-mass spectrometry confirmed that BIRM 270 inhibited arachidonate release from ionophore-stimulated neutrophils. The compound did not affect arachidonate reacylation. The blockage of arachidonate release coincided with inhibition of leukotriene B4 biosynthesis in these cells. BIRM 270 also inhibited ionophore-stimulated platelet-activating factor biosynthesis by human neutrophils. Although these results suggest that BIRM 270 inhibited phospholipase A2-mediated deacylation of membrane phospholipids, the compound did not directly inhibit the high molecular weight, cytosolic phospholipase A2 derived from human neutrophils or U937 cells. Thus, suppression of arachidonate mobilization by BIRM 270 may be due to indirect inhibition of intracellular phospholipase A2 or to inhibition of another acylhydrolase activity.

Arachidonic Acid↗

Renal stents.

Ureteral stents are used to promote drainage of the upper urinary tract. Although stents are used to relieve ureteral obstruction from any cause, they are most often placed due to obstruction by renal calculi. Ureteral stents may be placed emergently if obstruction is complicated by azotemia, infection, obstruction of a solitary kidney, or pain refractory to analgesia. Complications of renal stents include encrustation, migration, infection, pain and discomfort, urinary reflux, failure to properly drain, and hematuria. Serious complications are rare but include upward migration and infection leading to septic shock. Frequent complications include pain and discomfort and microscopic hematuria. Gross hematuria may occur as a result of erosion of a segment of the urinary tract. Emergency physicians can be expected to encounter patients with these complications of ureteral stents because of the widespread use of this prosthetic device.

Emergencies↗

Botulinum toxin therapy for blepharospasm in the otolaryngology clinic.

The use of botulinum toxin (Botox, Allergan, Inc.) is a treatment for spasmodic conditions involving many structures in the head and neck. Proper reconstitution, storage, preparation and administration of Botox are important aspects of its use. This article focuses on the actual preparation and sites of injection of Botox as well as the authors' clinical experiences in using it.

Anti-Dyskinesia Agents↗

Comprehensive geriatric assessment: a meta-analysis of controlled trials.

There is disagreement on the usefulness of comprehensive geriatric assessment (CGA) due to conflicting results from individual trials. We did a meta-analysis on 28 controlled trials comprising 4959 subjects allocated to one of five CGA types and 4912 controls. Published data were supplemented with reanalysed data provided by the original investigators. We calculated combined odds ratios of important outcomes by pooling data from individual trials with multivariate logistic regression. Combined odds ratio (95% confidence interval) of living at home at follow-up was 1.68 (1.17-2.41) for geriatric evaluation and management units, 1.49 (1.12-1.98) for hospital-home assessment services, and 1.20 (1.05-1.37) for home assessment services. Covariate analysis showed that programmes with control over medical recommendations and extended ambulatory follow-up were more likely to be effective. Our analysis suggests that CGA programmes linking geriatric evaluation with strong long-term management are effective for improving survival and function in older persons.

Activities of Daily Living↗

Inhibition of herpes simplex virus type 1 ribonucleotide reductase by substituted tetrapeptide derivatives.

It is known that peptides corresponding to the C-terminus of the small subunit of herpes simplex virus type 1 and 2 ribonucleotide reductase can inhibit enzymatic activity by preventing the association of the enzyme's two subunits. In a quest for smaller, more potent inhibitors, we have conducted a structure activity investigation based on the pentapeptide H-Val-Val-Asn-Asp-Leu-OH. Potency increases of up to 4000 times (IC50 0.18 microM) have been achieved in an enzymatic assay by a combination of modifying the N-terminal valine to a diethylacetyl group, adding a methyl group to the beta-carbon of the adjacent valine, dialkylating the asparagine side-chain nitrogen and dimethylating the beta-carbon of the aspartic acid residue. In addition the relative contribution of various inhibitor functionalities to inhibitor potency has been investigated.

Amino Acid Sequence↗

Earliest electrocardiographic evidence of myocardial infarction: implications for thrombolytic treatment. The GREAT Group.

OBJECTIVES: To determine the incidence of the earliest electrocardiographic changes in patients with suspected myocardial infarction and their sensitivity and specificity for predicting the final diagnosis of acute myocardial infarction. DESIGN: Retrospective study of paired electrocardiograms recorded at home and on admission to hospital. SETTING: 29 rural practices in Grampian and teaching hospitals in Aberdeen. PATIENTS: 137 patients participating in the early anistreplase trial in the Grampian region, who received placebo at home and for whom paired electrocardiograms were available. MAIN OUTCOME MEASURES: Classified electrocardiographic abnormalities and diagnosis at discharge. RESULTS: Electrocardiograms were recorded immediately before injection of placebo at home and anistreplase in hospital at median times of 110 and 240 minutes after the onset of symptoms. Definite or probable myocardial infarction was later confirmed in 93 (68%) patients. Of these, 66 (71%) had the same findings on both electrocardiograms of either ST elevation, bundle branch block, or a non-specific abnormality, while 27 (29%) showed a major change of classification between home and hospital recordings; 21 (23%) had ST elevation or bundle branch block on only one of the paired recordings. Although ST elevation was the commonest abnormality in the 93 patients with myocardial infarction, in only 51 was it recorded at home (sensitivity 55%) and in 49 on admission (sensitivity 53%). Of 57 patients with ST elevation at home, six did not have infarction (specificity 86%), while of 51 with ST elevation on admission, two did not have infarction (specificity 95%). CONCLUSIONS: Elevation of the ST segment is a transient electrocardiographic abnormality that has high specificity but low sensitivity for predicting the diagnosis of acute myocardial infarction; it is an unsatisfactory precondition for giving thrombolytic treatment to patients with suspected acute myocardial infarction.

Anistreplase↗

An overview of the diagnostic considerations in polycystic ovarian syndrome.

The past ten years have been particularly exciting with regard to the elucidation of the pathophysiology of PCOS. It appears that PCOS is about to yield some of its mysteries and to have some of its discrete subsets defined, as Cushing syndrome did 50 years ago. However, future studies of PCOS will require a complex interplay of clinical investigation, molecular and genetic probes, increasingly refined anatomic observations, and fundamental neuroendocrine studies. Each observer has a bias, which must be acknowledged in his/her studies. However, a true synthesis of the abnormalities characteristic of PCOS must continually be sought, for only through a comprehensive view of this syndrome will we come to understand its true pathophysiology; and only then can rational therapies be designed.

Androgens↗

Prostatic thermoluminescent dosimeter analysis in a patient treated with 18 MV X rays through a prosthetic hip.

External beam radiation therapy with high energy photon beams through hip prostheses has been shown to cause dose inhomogeneities for target volumes in the pelvis. In this work, measurements of dose using thermoluminescent dosimetry were compared with dose calculations from a computerized treatment planning system in a patient with prostatic carcinoma and a cobalt-chromium-molybdenum hip prosthesis. A 39% decrement in dose at isocenter was demonstrated for an 18 MV photon beam passing through the prosthesis. A discrepancy of only 3.1% was shown between measured and calculated dose when the tissue-maximum ratio (TMR) method of heterogeneity correction was used. However, it is recognized that several sources of error are possible when heterogeneity corrections are performed for high density prostheses and these are discussed below. The results of this work stress the importance of accurate data for use with the "ratio of TMR's" algorithm in order that accurate treatment planning can be performed.

Chromium↗

Effects of administration of anti-CD4 and anti-CD8 monoclonal antibodies on Mycobacterium paratuberculosis infection in intragastrically challenged mice.

In this study, we examined the roles of CD4+ and CD8+ cells in resistance to experimental paratuberculosis. Mice received purified anti-CD4 or anti-CD8 monoclonal antibodies before intragastric challenge with Mycobacterium paratuberculosis and on a biweekly basis for six months. This resulted in sustained depletion of CD4+ and CD8+ cells as verified by flow cytometry analysis of spleen cells from M. paratuberculosis infected mice. Depletion of CD4+ or CD8+ cells did not enhance fecal shedding of M. paratuberculosis, bacillary multiplication in the liver and ceca, nor histopathologic damage to the intestinal tract, mesenteric lymph nodes, spleen and liver. These data suggest that cells other than CD4+ or CD8+ cells are important for host defense in experimental paratuberculosis.

Animals↗

ERP abnormalities during semantic processing in schizophrenia.

To examine the neurophysiological and cognitive characteristics of thought disturbance in schizophrenic patients, we examined the amplitude, latency, and topography of a specific event-related brain potential (ERP), the N400, which is elicited by semantically incongruent words and phrases. Twelve chronic schizophrenic patients and twelve age-matched control subjects read sentences presented visually that had either semantically correct (e.g., 'People pray in their local church') or incorrect endings (e.g., 'Every Sunday morning people pray in their local nest'). Relative to normal controls, schizophrenic patients had significantly reduced N400 amplitude and increased latency to semantically anomalous endings. Additionally, a late positive component which follows the N400 was significantly reduced in amplitude in schizophrenic patients. However, patients and controls did not differ significantly in terms of the topographical distribution of either the N400 or its late positive potential, examined at 28 electrode sites. Thus, N400 topography in schizophrenic patients was not accompanied by the asymmetry which frequently characterizes the well known auditory P300 disturbance in schizophrenic patients. We concluded that these findings may reflect a profound disturbance in attentional processes in chronic schizophrenia.

Adult↗

Necrobiosis lipoidica diabeticorum: association with background retinopathy, smoking, and proteinuria. A case controlled study.

In order to evaluate patients with necrobiosis lipoidica diabeticorum and to compare them with age, sex, and duration of diabetes matched controls, 15 patients with necrobiosis were each matched with 5 control subjects with diabetes mellitus. Complications of diabetes, glycaemic control, and proteinuria were measured. Patients with necrobiosis (mean age 40, range 18-74 years) had a mean duration of diabetes of 14 (range 3-36) years; 8 patients were male, and 7 were female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p = 0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003) were all more common with necrobiosis. There were no significant differences between patients with necrobiosis and control patients in the prevalence of vascular disease and neuropathy. Glycosylated haemoglobin concentrations were higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were similar in both groups. We conclude that smoking, proteinuria, and retinopathy were more prevalent in diabetic patients with necrobiosis; the skin lesion may therefore share common aetiological factors which affect the microvascular circulation, leading to damage to basement membranes and vascular endothelial cells.

Adult↗