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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Dose titration during anti-thymocyte globulin therapy: monitoring by CD3 count or total lymphocyte count?

Anti-thymocyte globulin (ATG) is extensively used for both prophylaxis and treatment of rejection episodes in renal transplantation, but it is expensive and potentially hazardous. We report the utility of therapeutic monitoring by the readily available total lymphocyte count, compared with the more complex and expensive assay of CD3 counts by flow cytometry in eight renal transplant patients receiving ATG. Aiming for an absolute CD3 count of 0.2-0.5 x 10(9)/l, it was possible to reduce the mean daily dose of ATG from the recommended 2.5 mg/kg/d to a mean of 1.6 mg/kg/d. Analysis of simultaneously taken total lymphocyte counts showed that the same dose reductions could have been made if the target for therapeutic effect had been a total lymphocyte count of < 0.3 x 10(9)/l. Anti-rejection therapy was successful in all cases, with satisfactory graft function at 6-9 months post-therapy. Lower than recommended doses of ATG proved effective prophylaxis and treatment of renal allograft rejection, with considerable cost savings. A simple protocol may be followed titrating dose against total lymphocyte count, provided it remains below 0.3 x 10(9)/l. CD3 estimation can be reserved for those times when the total lymphocyte count rises to 0.3 x 10(9)/l or above.

Antigens, CD19↗
PubMed1997

Capillary filtration coefficient and urinary albumin leak at altitude.

Rapid ascent to altitude risks the development of acute mountain sickness. This study demonstrates changes in peripheral capillary filtration coefficient and renal protein loss in subjects suffering from various degrees of mountain sickness after passive ascent to 4559 m. Capillary filtration coefficient of the calf capillary bed, measured by computer-based multistep strain gauge plethysmography, increased significantly after 23.5 h at altitude when symptoms were most severe: 4.45 (2.76-6.03) to 6.31 (3.86-11.07) ml min(-1) per 100 g of tissue mmHg(-1), median (range) (P < 0.02). Urinary albumin excretion was increased after one night at altitude from 1.1 (0.6-1.5) to 2.45 (1.0-6-8) mg of albumin per mmol of creatinine (P < 0.05). These results demonstrate simultaneous leakage of a peripheral capillary bed to fluid measured by strain gauge plethysmography, and renal albumin leak, and suggest a systemic process of increased capillary leakage for different-sized molecules caused by rapid exposure to hypobaric hypoxia.

Adult↗
PubMed1997

Report of a gingival "surgical cyst" developing secondarily to a subepithelial connective tissue graft.

The subepithelial connective tissue graft is a valuable technique used to cover exposed root surfaces or to increase the zone of attached gingiva. Cysts, such as the gingival cyst of the adult, are epithelial-lined cysts which may arise from heterotropic glandular tissue, a proliferating rete peg, remnants of the dental lamina, or traumatic implantation of epithelial tissue. In this paper, a case report is described of a "surgical cyst" or cystic morphogenesis of surgically implanted epithelium developing secondarily to a subepithelial connective tissue graft.

Aged↗
PubMed1996

Hypoglycemic activity of a series of alpha-alkylthio and alpha-alkoxy carboxylic acids related to ciglitazone.

The thiazolidinedione moiety of ciglitazone and its analogues can be replaced by an alpha-alkoxy or alpha-thioether carboxylic acid group. The influence of the nature of the R group, the length of the connector to the aromatic backbone of the molecule, and the stereochemistry have been studied. The most potent compounds have glucose-lowering activity at doses as low as 0.01 mg/kg.

3T3 Cells↗
PubMed1996

Interim review of the Transnational Case-control Study of Oral Contraceptives and Health: approved protocol revisions through September 1995.

UNLABELLED: The protocol of the Transnational Study on Oral Contraceptives has been published at the outset of the study in order to ensure the correct performance of the study and to ensure the study's scientific integrity. Potential revisions and additions to this protocol had been announced in the prior publication. This article focuses on those points of protocol which have been resolved as practical experience was gathered as well as additional modifications required by practical and scientific considerations. The major alterations are based on exposure prevalences in controls and on power calculations. The low (1.8%) exposure to gestodene among German controls led to the discontinuation of the German component and to the accelerated accession in additional countries. THE CASE: control ratio was altered to 3:1 for purposes of economy based on power calculations. Numerous minor points, most addressed in the prior protocol, have been resolved. It is found that these modifications of the study protocol do not impair the study's conduct, its scientific integrity, nor its capability of providing answers to the study question.

Journal Article↗
PubMed1996

Disturbance of peripheral microvascular fluid permeability by the onset of atrioventricular asynchrony in patients with programmable pacemakers.

BACKGROUND: In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. OBJECTIVES: To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. PATIENTS: 12 patients with programmable dual chamber permanent pacemakers. METHODS: Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. RESULTS: Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. CONCLUSIONS: The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.

Adult↗
PubMed1996

Validity and reliability issues in published public health and social policy research.

This paper reviews basic measurement concepts associated with objective instruments, argues for the importance of addressing the validity and reliability of instruments in articles reporting the results of empirical research, and discusses common measurement issues through examples observed in public health and social policy journals.

Attitude to Health↗
PubMed1996

Report of a lateral periodontal cyst and gingival cyst occurring in the same patient.

The lateral periodontal cyst and gingival cyst of the adult are both developmental odontogenic cysts located predominantly in the mandibular premolar-canine region. In this paper, a case report is described of a lateral periodontal cyst and gingival cyst occurring in the same patient along with a discussion of clinical, radiographic, and histological features of these lesions.

Gingival Diseases↗
PubMed1995

Effects of age on aneural regeneration of soleus muscle in rat.

1. The ability of autografted soleus muscles to regenerate without innervation was investigated in young (two groups: 17 days or 35 g and 5 weeks or 100 g) and old (10 weeks or 300 g and 19 months or 700 g) rats. 2. Tetanic force and fibre area of the regenerated muscles were followed in 35, 100 and 300 g rats and found to reach a maximum 10-15 days after the operation and then declined. 3. Maximal tetanic force and fibre area were greater in old than in young rats; the largest increase was seen between 100 and 300 g rats. The relaxation phase of the twitch became shorter in the 700 g animals. The force per cross-sectional area appeared to fall with age. The length of the new fibres, inferred from the width of the length-force curve, increased only slightly with age. 4. Ten days after grafting, autophagocytosis of necrotic fibres was completed in young but not in old rats. The new fibres in young rats had one central nucleus per cross-section and fibre size was unimodally distributed; fibres in old rats had multiple internal nuclei and the size distribution was bimodal due to the presence of large fibres. 5. Previous results indicating greater muscle regeneration in young than in old rats may reflect more vigorous reinnervation in young animals rather than a greater myogenic potential. Increased fibre size of regenerated muscles of old compared with young rats may be attributed to the larger amount of necrotic material which is mitogenic for satellite cells, or to age-dependent changes of the expression of cell adhesion molecules. Enhanced lateral fusion of myotubes would give rise to large fibres with multiple internal nuclei.

Aging↗
PubMed1995

Chemotaxis of alveolar macrophages and neutrophils in response to microbial products derived from organic dust.

The inhalation of organic dust has been implicated to cause a large number of occupational lung diseases. A common event in these diseases is an inflammatory reaction affecting airway and alveolar tissue that is characterized by the recruitment of different types of inflammatory cells. Mechanisms of chemotaxis of alveolar macrophages (AMs) and neutrophils (PMNs) in response to microbial products derived from organic dust were studied. Seven agents known to be etiological agents causing respiratory symptoms (extract and endotoxin of Enterobacter agglomerans, extracts from Thermoactinomyces vulgaris and Aspergillus fumigatus, thermophilic protease, and two preparations of glucans) were used for experiments. These agents were evaluated for their ability to directly attract AMs and PMNs and to stimulate alveolar macrophages to release chemotactic factors for other AMs and PMNs. The microbial products were able to attract both AMs and PMNs directly in a dose-dependent manner and the exposure of cultured AMs to most agents were stimulatory for production of chemotactic activity for AMs and PMNs. The generation and release of this activity by AMs may provide a mechanism for the initiation and amplification of inflammatory reactions in the lung after inhalation of organic dust. Results of these in vitro studies may be relevant to the pathogenesis of alveolitis in organic dust-induced lung diseases.

Air Microbiology↗
PubMed1994

A sensitive new bioassay for tumor necrosis factor.

Tumor necrosis factor is an important cytokine involved in inflammation and assay of this cytokine in biological fluids may be important in the understanding of several disease processes. This report describes an improved TNF bioassay employing a newly isolated subclone of the cell line NCTC-clone 929 as well as a novel fluorescence indicator system for detecting viability of the target cells. The limit of detection for the TNF hypersensitive cell line with this fluorescence viability assay was 68 +/- 2.5 fg/ml, which is approximately 3 x more sensitive than the parental clone and approximately 10 x more sensitive than that reported by Branch et al. (1991) using the neutral red indicator system. The hypersensitivity of the clone gradually declined over a 45-day period and at regular intervals new cells were cultivated from frozen stocks. Two different serum sources, bovine fetal serum and horse serum, and four different serum concentrations (5, 10, 15, 20%) were evaluated to optimize sensitivity. No difference was found between serum sources but sensitivity was significantly reduced if < 15% serum was used.

Animals↗
PubMed1994

Oxidative susceptibility of low density lipoprotein subfractions is related to their ubiquinol-10 and alpha-tocopherol content.

The conjugated polyene fatty acid parinaric acid (PnA) undergoes a stoichiometric loss in fluorescence upon oxidation and can be used to directly monitor peroxidative stress within lipid environments. We evaluated the course of potentially atherogenic oxidative changes in low density lipoproteins (LDL) by monitoring the oxidation of PnA following its incorporation into buoyant (p = 1.026-1.032 g/ml) and dense (p = 1.040-1.054 g/ml) LDL subfractions. Copper-induced oxidation of LDL-associated PnA exhibited an initial lag phase followed by an increased rate of loss until depletion. Increased PnA oxidation occurred immediately after the antioxidants ubiquinol-10 and alpha-tocopherol were consumed but before there were marked elevations in conjugated dienes. Despite differences in sensitivity to early oxidation events, PnA oxidation and conjugated diene lag times were correlated (r = 0.582; P = 0.03), and both indicated a greater susceptibility of dense than buoyant LDL in accordance with previous reports. The greater susceptibility of PnA in dense LDL was attributed to reduced levels of ubiquinol-10 and alpha-tocopherol, which were approximately 50% lower than in buoyant LDL (mol of antioxidant/mol of LDL) and together accounted for 80% of the variation in PnA oxidation lag times. These results suggest that PnA is a useful probe of LDL oxidative susceptibility and may be superior to conjugated dienes for monitoring the initial stages of LDL lipid peroxidation. Differences in oxidative susceptibility among LDL density subfractions are detected by the PnA assay and are due in large part to differences in their antioxidant content.

Adult↗
PubMed1994

Superoxide anion production in response to bacterial lipopolysaccharide and fungal spores implicated in organic dust toxic syndrome.

High amounts of fungal spores, bacteria, and bacterial endotoxin have been found in dust associated with the poorly characterized syndrome, organic dust toxic syndrome (ODTS). As part of an ongoing investigation to determine the etiopathogenesis for ODTS, this study has focused on activation of guinea pig bronchial alveolar lavage (BAL) cells as evidenced by the production of superoxide anion in response to fungal spores and lipopolysaccharide (LPS). Fungal spores from Aspergillus candidus, Aspergillus terreus, Aspergillus niger, Aspergillus fumigatus, Eurotima amstelodami, Penicillium spinulosum, and Cladosporium cladosporioides were all shown to increase superoxide anion production, each with different potencies. LPS stimulated little superoxide anion production in BAL cells, but when cells were pretreated with LPS prior to stimulation with fungal spores, superoxide anion production was increased over that induced by either spores or LPS alone. These results suggest that the inhalation of LPS together with fungal spores could possibly provoke abnormal lung pathologies.

Air Microbiology↗
PubMed1994

A comparison of the morphology of denervated with aneurally regenerated soleus muscle of rat.

Soleus muscles of rats were denervated, treated with bupivacaine and autografted in order to induce aneural regeneration or only denervated. After 2-70 days, muscles were fixed and embedded in epoxy resin for light and electron microscopy. Regenerating muscles after 2 and 5 days consisted of a necrotic core and a rim of new fibres; the necrotic core had disappeared by day 10. The fibre size (mean cross-sectional area) was 139 microns2 after 10 days; it decreased to 22 microns2 after 70 days. Denervated muscle fibres measured 26 microns2 after 70 days. The sarcomere pattern was regular in 10-day regenerates but later degenerated. There were signs of fibre breakdown; immature regenerating fibres were still found after 70 days. Denervated muscles already contained a few new myotubes at 10 days; at 40 and 70 days fibre loss and regeneration were distinct. The percentage of satellite cells relative to myonuclei (normal 8%) doubled within the first 10 days after necrosis and then fell to less than one fourth of normal. Denervation for 70 days increased threefold the percentage of satellite cells in some muscles and in others caused a decrease to half of normal. The number of fibre cross-sections in regenerated muscles was about 3000 after 10-70 days; this was roughly the same number as in normal soleus muscles. The true number of fibres, however, may have been smaller because regenerated fibres tend to branch. It is concluded that aneurally regenerating muscle fibres reach a high degree of structural differentiation, but then atrophy, degenerate and vanish; they are replaced by new fibres, which do not reach the size of the first fibres, presumably because the satellite cell pool without innervation eventually becomes exhausted. The slow and non-synchronized breakdown of denervated soleus muscle fibres induces proliferation of satellite cells as in necrotized muscles; those muscles which had fewer satellite cells than normal after 70 days might already be showing exhaustion.

Animals↗
PubMed1994

Contractile properties of aneurally regenerated compared with denervated muscles of rat.

The time course of aneural regeneration in slow-twitch soleus muscles of young adult rats was studied and compared with the changes following denervation in soleus and fast extensor digitorum longus muscles. Regeneration was induced by auto-grafting after treatment with bupivacaine; isometric contractions were recorded from 5 to 70 days later. Force was detected at 5 days; at 12 days force was maximal (at least 20% of original) and thereafter fell exponentially. Force varied normally with total fibre area, except at 5 and 71 days when force generating capacity was low. Contraction and relaxation in the twitch were longer than normal (maximally at 5 days), and were closer to denervated soleus than EDL; in contrast, the maximal rate of rise of force was as high as that of denervated EDL and much higher than in denervated soleus. It is suggested that the muscle was fundamentally fast contracting, but the twitches were probably slow because of greater than normal activation following a single stimulus--a hypothesis supported by twitch:tetanus ratios that were higher than in denervated muscles. Tetanic force was much more sensitive than normal to changes of muscle length from optimum, despite the fact that the lengths of regenerated muscles were similar to those of contralateral muscles. The properties of denervated soleus gradually approached those of regenerated soleus, probably because of replacement of original fibres by regenerated ones.

Animals↗