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Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 289 records · Page 16Linked to original sources

Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation.

Using limiting dilution analysis, we investigated proliferative responses of UCHL1+ and UCHL1- T cell populations to compare the precursor cell frequencies following recall and alloantigen stimulation, and the complexity of cellular interactions within UCHL1+ and UCHL1- populations. We find high frequencies of recall antigen responses among UCHL1+, but not UCHL1- T cells. In contrast, both populations contain similar frequencies of alloantigen responsive cells. Our results are consistent with single-hit kinetics in recall as well as alloantigen responses and show no complex cellular interactions within the responding populations. In conclusion, the difference between the recall antigen response of UCHL1+ and UCHL1- cells observed in conventional proliferation assays is most probably due to a high frequency of recall antigen-responsive UCHL1+ cells and not to suppressive phenomena in the UCHL1- population. These data suggest that memory T cells are largely of the UCHL1+ phenotype. The relation of post-thymic T cell maturation and differential CD45 expression is briefly discussed.

Antibodies, Monoclonal↗

High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas.

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.

Adenocarcinoma↗

The in-vitro degradation at 37 degrees C of vancomycin in serum, CAPD fluid and phosphate-buffered saline.

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.

Bacteriological Techniques↗

Laboratory assessment of lomefloxacin (SC-47111) in comparison with norfloxacin.

The activity of lomefloxacin and norfloxacin against 681 bacterial strains, including 520 strains isolated from infected urine was assessed in vitro. All strains were tested in two inocula and the susceptibility of urinary isolates was evaluated at three pH levels. Lomefloxacin displayed a broad spectrum of antibacterial activity which was similar to that of norfloxacin and which was independent of inoculum size. Good activity was shown for lomefloxacin against all Gram-negative urinary pathogens: strains of Pseudomonas spp and nalidixic acid-resistant enterobacteria were the least susceptible, indicating a degree of cross resistance between newer quinolones and nalidixic acid. Lomefloxacin generally showed more modest activity against Gram-positive cocci and bacteroides than against enterobacteria. Under the acidic conditions that commonly prevail in urine the activity of both compounds against Gram-negative urinary pathogens was markedly reduced, whereas strains of Gram-positive cocci were only minimally affected.

Anti-Bacterial Agents↗

Surgical treatment of burns in elderly patients.

This study evaluates our experience with surgical treatment of burns in the elderly. Forty-two patients more than 59 years old were treated from 1982 to 1986. The mean age was 73, and the mean TBSA burned was 29%. The patients were divided into three groups. Group I had 22 patients with less than 20% TBSA burn (mean of 11%, with a mean of 6% full-thickness burns). Their survival rate was 91%. Group II had 11 patients with 21-40% TBSA burns (mean of 32%, with a mean of 17% full-thickness burns). Their survival rate was 82%. Group III had nine patients with burns greater than 40% TBSA (mean, 71%). None of these patients survived. Twenty of 29 (68%) survivors required a total of 36 operations. The mean area grafted per procedure was 8%. Each procedure required a mean of 2U packed red blood cells, and a mean of 2 1/4 hours. The complication rate was 33%, with partial graft loss (14%) being the most frequent. The average hospital stay was 27 days in Group I and 45 days in Group II. Only 25% of the patients required nursing home assistance at discharge.

Aged↗

Psychosexual trauma of an abnormal cervical smear.

The psychosexual sequelae of diagnosis and treatment of pre-invasive cervical atypia were assessed in three groups of women. The first group included 30 women referred to a colposcopy clinic with an abnormal cervical smear indicating cervical intraepithelial neoplasia (CIN), the second comprised 50 women who were traced as sexual partners of men with penile human papillomavirus (HPV) infection; 26 of them had histologically proven cervical atypia and 24 had no such evidence. The third group included 25 women traced as partners of men with non-specific urethritis and who did not have cervical disease. Before and after questionnaires assessed six aspects of sexual behaviour and responses before diagnosis and 6 months after treatment in women with cervical atypia. These were compared with answers given by women investigated and treated, if necessary, as partners of men with sexually transmitted disease (control group). There were statistically significant adverse psychosexual sequelae associated with diagnosis and treatment of pre-invasive cervical epithelial disease.

Adult↗

The organization of cervical screening in general practice.

Well organized cervical screening in general practice can have considerable clinical and financial rewards. Yet in a randomized survey of general practitioners in the United Kingdom only 43% operated a system for cervical screening which allows previously untested women to be identified and invited for testing.A younger age of general practitioner, a more rural practice, a larger practice size, employment of a practice nurse, a belief in the effectiveness of cervical screening and a positive view of the time spent on screening were all strong predictors of an organized approach to cervical screening within a practice. Being female or having a female partner was not statistically associated with systematic screening. The results demonstrate a need for education within general practice which emphasizes the relevance and significance of cervical screening and the essential contribution that can be made by each individual general practitioner to the success of the whole cervical screening programme.

Adult↗

Studies of lipoproteins and fatty acids in maternal and cord blood of two racial groups in Trinidad.

The high mortality rate from coronary heart disease (CHD) among Indians compared to Negroes in Trinidad led us to test plasma lipid profiles to see whether dietary or genetic factors might be involved. There were no interracial differences in the composition of plasma cholesterol ester fatty acids of the tested women and neonates. This finding suggests that dietary fat does not account for the interracial difference in CHD, nor does the cause appear to be due to genetic differences in lipid profiles, as there was no significant difference between values for plasma triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, apo-I, apo-II, apo B or cholesterol ester fatty acids in the cord blood of each racial group. Blood samples were collected from 69 nonpregnant and 71 postpartum, fasted Negro and Indian women. Also taken were 71 umbilical cord blood samples. The mean triglyceride level was significantly lower in the Negro nonpregnant and postpartum women than in the Indians. HDL cholesterol and apo-I values were lower in the Indian women. There were no significant differences in the total cholesterol and apo B measurements. The triglyceride values for postpartum women were higher than those of the nonpregnant Negroes and Indians (75% and 47%, respectively), whereas the total cholesterol and HDL cholesterol, apo A-I and apo A-II ranged from 9% to 29% higher in the postpartum women. Apo B was about 40% higher postpartum in both ethnic groups. The high CHD rate of Indians in Trinidad cannot be explained by dietary factors, plasma total cholesterol or fatty acid composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pseudomonas peritonitis in continuous ambulatory peritoneal dialysis: laboratory predictors of treatment failure.

Five episodes of pseudomonas peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) which were not cured by intraperitoneal antibiotics were studied to assess causes for treatment failure. The activity of gentamicin and ceftazidime against these strains was decreased in the presence of sterile used dialysate compared with nutrient broth. Likewise, kinetic studies showed that in dialysate therapeutically used concentrations of antibiotics failed to kill the isolates over 24 h. All five pseudomonas strains were adherent to silicone rubber Tenckoff catheter segments. An in vitro model of CAPD peritonitis demonstrated that persistence of viable adherent bacteria, after exposure to therapeutic concentrations of gentamicin and ceftazidime, contributes to the failure of antibiotics to cure pseudomonas CAPD peritonitis.

Adult↗

Potent vasopressin antagonists modified at the carboxy-terminal tripeptide tail.

In a continuing effort to design more potent renal vasopressin (V2 receptor) antagonists, we have focused our attention on the carboxy-terminal tripeptide tail (Pro-Arg-Gly-NH2), a fragment common to both agonists and antagonists. Vasopressin antagonist analogues having a dibasic dipeptide tail, e.g., Arg-Arg-NH2 or Arg-Lys-NH2, attached directly to the cyclic hexapeptide ring are potent V2-receptor antagonists. Similar modification of a representative agonist drastically reduces its potency. We report the synthesis and pharmacological properties of a series of potent V2-receptor antagonists 3-9 where a combination of D or L dibasic dipeptide has been utilized to replace the common tripeptide fragment. Our results suggest a difference in the way agonists and antagonists bind to vasopressin receptor and further support the difference in the structure-activity relationships of agonists and antagonists. These results provide potentially useful insights for the design of novel V2-receptor antagonists.

Animals↗

Pharmacokinetics of single dose intravenous vancomycin in CAPD peritonitis.

The pharmacokinetics of single dose intravenous vancomycin (25 mg/kg) were studied in six patients with peritonitis complicating continuous ambulatory peritoneal dialysis. The volume of distribution after equilibration was 1.1 +/- 0.1 l/kg (mean +/- standard error) with a serum elimination half-life of 115 +/- 6 h. The peritoneal clearance was 1.4 +/- 0.5 ml/min and the serum clearance was 7.2 +/- 0.3 ml/min. Mean peak serum levels of 56.8 +/- 4.7 mg/l were detected. Initial mean overnight dialysate level was 12.3 +/- 0.8 mg/l. Vancomycin dialysate levels of 8 mg/l were achieved for a mean of 3.0 days and levels of 4 mg/l for a mean of 6.2 days. Single dose intravenous vancomycin may, therefore, have therapeutic value in selected patients.

Aged↗

Mouse nerve growth factor gene: structure and expression.

The organization and biologically significant sequences of the entire mouse nerve growth factor (NGF) gene have been determined. The gene spans 45 kilobases and contains several small 5' exons. Transcription of the gene results in four different mRNA species, which can be accounted for by alternative splicing and independent initiation from two promoters. These transcripts encode proteins which have divergent N termini and the NGF moiety at their C termini. The levels of the various NGF transcripts have been determined in different tissues and throughout postnatal development. We have also examined the expression of these transcripts in the brain in response to specific early sensory deprivation. The results suggest that the expression of NGF mRNA during postnatal development is regulated independently of the formation of complex neural networks.

Age Factors↗

The toxicity and metabolism of the pyrethroids cis- and trans-cypermethrin in rainbow trout, Salmo gairdneri.

1. The toxicity of cis- and trans-cypermethrin to rainbow trout was investigated and the concentrations of the two isomers in brain associated with toxic signs (excitability and loss of equilibrium) were determined. cis-Cypermethrin and trans-cypermethrin were equally toxic and showed similar brain levels associated with toxic signs (cis:0.25 micrograms/g, mean (range 0.07-0.53); trans:0.17 micrograms/g (0.07-0.31]. 2. Orally administered cypermethrin was less toxic than predicted, probably due to poor intestinal uptake. Toxicity was due to absorption via the gills of unchanged pyrethroid excreted from the intestine into the water. 3. The metabolism of the radiolabelled insecticides, [14C-cyclopropyl]- and [14C-benzyl]-cis- and trans-cypermethrin has been investigated in vivo and in vitro. 4. The principal route of elimination in vivo was the bile, with 20-28% dose excreted as biliary metabolites in 24 h. No difference in the rates of elimination of the cis and trans isomers was observed. 5. cis-Cypermethrin was metabolized primarily to the glucuronide of 4'-hydroxy-cypermethrin (80% total bile radioactivity), together with dichlorovinyldimethylcyclopropanecarboxylic acid and its glucuronide, 3-(4-hydroxyphenoxy)benzoic acid (4'-hydroxy-3BPA) and its ester and ether glucuronides, 3-phenoxybenzoyl glucuronide and 4'-hydroxy-3BPA sulphate were detected. trans-Cypermethrin was metabolized to the same products, but with only 36% as 4'-hydroxy-cypermethrin glucuronide.

Animals↗

In-vitro evaluation of antifungal agents in the treatment of yeast peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).

This study compared the static and kinetic activities of six antifungal agents, in broth and used dialysate, against six yeast strains known to have caused peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). Minimum inhibitory concentrations (MIC) and IC50 results show a trend towards greater activity by amphotericin B, 5-fluorocytosine, tioconazole and itraconazole in comparison to miconazole and ketoconazole although there was some strain variability. Minimum fungicidal concentrations (MFCs) of amphotericin B were less than or equal to 1mg/l, while 5-fluorocytosine and the azoles showed large discrepancies between MIC and MFC values. In kinetic studies amphotericin B was the most potent fungicidal agent. 5-fluorocytosine showed modest activity and failed to achieve total killing. The azoles demonstrated variable degrees of inhibition of C. glabrata and showed minimal activity with C. albicans. Itraconazole showed good activity against C. parapsilosis in broth. All agents, with the exception of 5-fluorocytosine, showed reduced activity in used dialysate in comparison to broth.

Amphotericin B↗