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Biomedical subjects

C Evans

Publications and source records attributed to C Evans.

At least 127 records · Page 7Linked to original sources
PubMed1995

Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer.

PURPOSE: Phase II studies have shown that the combination of interferon alfa-2b (IFN) and fluorouracil (5-FU) is active in patients with metastatic colon cancer. This study was designed to investigate whether treatment with the combination of IFN and 5-FU could improve the response rate, duration of response, or survival compared with treatment with 5-FU alone. PATIENTS AND METHODS: Patients with histologically confirmed advanced colorectal cancer were randomized to receive 5-FU 750 mg/m2/d by continuous infusion for 5 consecutive days followed by weekly bolus 5-FU 750 mg/m2 either with or without IFN 10 MU subcutaneously three times weekly. Treatment was continued until disease progression or unacceptable toxicity for up to 12 months. RESULTS: Radiologic response was observed in 26 of 106 assessable patients (25%): 10 of 52 (19%) in the group that received 5-FU plus IFN (all partial responses [PRs]) and 16 of 54 (30%) in the 5-FU-alone group (three complete responses [CRs] and 13 PRs) (P = .21). There was similarly no significant difference between the two groups in progression-free survival (median, 3 months), 1-year survival, or overall survival (median, 8 months). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .013), lymphopenia (P = .01), depression (P = .014), and alopecia (P = .002), and were significantly more likely to be withdrawn due to adverse events (P = .003). There were four toxic deaths, all of which occurred in patients who had received IFN. CONCLUSION: At the doses and schedules used in this study, IFN affords no benefit to 5-FU in terms of response and survival and significantly increases toxicity for patients with advanced colorectal cancer.

Adult↗
PubMed1995

A randomized study comparing visual laser ablation and transurethral evaporation of prostate in the management of benign prostatic hyperplasia.

PURPOSE: We evaluated the safety, efficacy, failure and complications of 2 techniques of laser prostatectomy for benign prostatic hyperplasia (BPH): transurethral evaporation of the prostate (evaporation) versus visual laser ablation of the prostate (coagulation) in a randomized trial. MATERIALS AND METHODS: A total of 64 consecutive patients with symptomatic BPH was randomized to undergo evaporation (32) or coagulation (32). American Urological Association symptom score, peak urinary flow rate and post-void residual urine volume were measured at baseline, and at 1, 3, 6 and 12 months. Other parameters evaluated included prostate volume by transrectal ultrasound, total laser energy per patient and per cc volume of the prostate, number of laser fibers per prostate, duration of catheterization and hospitalization, need for re-catheterization, and failure and complication rates. RESULTS: Our main findings were that patients undergoing laser prostatectomy using the coagulation technique (visual laser ablation of the prostate) had higher reoperation rates (16% versus 0%, p = 0.0199) and were 4 times more likely to have prolonged postoperative urinary retention (25% versus 6.3%, p = 0.0389), evaporation and coagulation were effective at relieving symptoms of prostatism with significant improvement in American Urological Association symptom scores and post-void residual urine volumes compared to baseline, improvement in peak flow rates was significantly greater in patients undergoing evaporation at 1, 3, 6 and 12 months (p < 0.001) compared to coagulation, and a significantly greater amount of laser energy was required to evaporate a unit volume of prostate tissue compared to coagulation (2,251 J./cc versus 1,036 J./cc, p < 0.03). CONCLUSIONS: Between the 2 major techniques of laser prostatectomy, transurethral evaporation is associated with better results at up to 12 months of followup.

Aged↗
PubMed1994

Preparation and kinetic characterization of a fusion protein of yeast mitochondrial citrate synthase and malate dehydrogenase.

We have expressed the DNA of the fusion of CS1 to MDH1 in Escherichia coli gltA-. The fusion protein (CS1/MDH1) is the C-terminus of CS1 linked in-frame to the N-terminus of MDH1 with a short linker of glycyl-seryl-glycyl. The fusion protein produced was isolated and purified. Gel filtration studies indicated that CS1/MDH1 had a M(r) of approximately 170,000. Western blotting analysis with SDS gel indicated a M(r) of approximately 90,000-95,000 (theoretical M(r) = 87,000). This is the expected M(r) for the fusion protein subunit. The kinetics of CS1 and MDH1 activities of the fusion protein were compared to those of the free enzymes. In addition, the effect of AAT reaction, as a competitor for the intermediate OAA of the coupled MDH-CS reaction, was examined. It was observed that AAT was a less effective competitor for OAA when the CS1/MDH1 fusion protein is used than when the separate enzymes are employed. In addition, the transient time for the coupled reaction sequence was less for the fusion protein than for the free enzymes.

Aspartate Aminotransferases↗
PubMed1994

Coronary artery disease and coronary artery bypass grafting in diabetic patients aged > or = 65 years (report from the Coronary Artery Surgery Study [CASS] Registry).

A cohort of 317 diabetic patients, aged > or = 65 years, with angiographically proven coronary artery disease, was analyzed and followed for a mean of 12.8 years. Compared with 1,843 age-matched nondiabetic patients, diabetic patients were more likely to (1) have a higher number of coronary occlusions, (2) not be current smokers, (3) have higher systolic but lower diastolic blood pressures, (4) have evidence of peripheral vascular disease, and (5) be women. They did not differ significantly with respect to total cholesterol, family history of coronary artery disease, history of hypertension, or left ventricular hypertrophy. In the total elderly cohort, diabetes was found to be an independent predictor of mortality, conferring a 57.0% increased risk of death. Survival analysis showed that diabetic subjects consistently had higher mortality than nondiabetics. However, the relative survival benefit of coronary artery bypass graft surgery versus medical therapy was comparable in diabetic and nondiabetic patients. Surgical therapy conferred a reduction in mortality of 44%.

Aged↗
PubMed1994

Nitric oxide mediates suppression of cartilage proteoglycan synthesis by interleukin-1.

Slices of rabbit articular cartilage synthesized large quantities of nitric oxide (NO) following exposure to human recombinant interleukin-1 beta (hrIL-1 beta) or rabbit synovial cytokines (CAF). Each of these stimuli also strongly suppressed the biosynthetic incorporation of 35SO4(2-) into the glycosaminoglycans (GAGs) of cartilage proteoglycans. Treatment of cartilage fragments with L-NG-monomethylarginine (L-NMA), a competitive inhibitor of NO synthase, both inhibited NO synthesis in response to IL-1 and CAF and restored proteoglycan synthesis. D-NMA was inactive in this regard, and L-arginine reversed the effects of L-NMA. S-nitrosylacetylpenicillamine (SNAP), an organic donor of NO, reversibly mimicked the effect of IL-1 and CAF on 35SO4(2-) incorporation. These data suggest that endogenously synthesized NO is the mediator which reduces cartilage proteoglycan synthesis in response to cytokines such as IL-1 and CAF. Antagonists of NO production may promote cartilage matrix synthesis and thus have potential as chondroprotective or chondroreparative agents.

Amino Acid Oxidoreductases↗
PubMed1994

Natural and synthetic CCK-58. Novel reagents for studying cholecystokinin physiology.

CCK-58 is a unique reagent for testing how segments of a peptide far removed from its active site can influence the expression of its biological activity. Indications of tertiary structure have come from studies with natural peptide purified from canine small intestine. These studies gave clear indications that tertiary structure affects CCK-58 bioactivity, but the small quantities of CCK-58 available made it impossible to characterize completely how tertiary structure influenced bioactivity. Canine CCK-58 was synthesized manually using a solid support and was purified by reverse phase high pressure liquid chromatography (HPLC). Synthetic CCK-58 was characterized by isocratic reverse phase and gradient HPLC, amino acid analysis, mass spectral analysis, sequence analysis, and three bioassays. Synthetic and natural canine CCK-58 had the same elution profiles, amino acid composition, sequence, and mass. The two peptides were equipotent for the stimulation of pancreatic secretion. Natural canine CCK-58 was equipotent to CCK-8 for CCK "B" receptor binding, a further indication of the purity of the natural peptide. However, natural CCK-58 was more potent than CCK-8 for CCK "A" receptor binding and less potent than CCK-8 for stimulation of pancreatic secretion. These data support the concept that CCK-58 has a stable tertiary structure. This structure does not affect its binding to CCK "B" receptors, enhances its binding to low affinity CCK "A" receptors, and decreases its activity expressed through binding to high affinity CCK "A" receptors. The concept of a stable tertiary structure is also supported by the fact that many antibodies directed towards the carboxyl terminus of cholecystokinin react better with CCK-8 than CCK-58. The availability of synthetic CCK-58 will allow analysis of its tertiary structure by physical and chemical methods as well as studies on how peptide tertiary structure can affect receptor binding, receptor activation, metabolism in blood, degradation in interstitial fluid, and inactivation at the receptor. Evaluating all of these systems will help investigators understand the regulation of cholecystokinin activity by its major endocrine form, CCK-58.

Amino Acid Sequence↗
PubMed1994

Effect on ligand binding of arginine mutations in recombinant rat liver fatty acid-binding protein.

Rat liver fatty acid-binding protein is able to accommodate a wide range of non-polar anions in addition to long-chain fatty acids. The two arginine residues of rat liver fatty acid-binding protein, Arg122 and Arg126, have been mutated and the effect of mutation on ligand binding investigated. No significant decrease in affinity for the fluorescent fatty acid analogue, 11-(5-dimethylaminonaphthalenesulphonyl amino)undecanoic acid, or oleate was observed. However, the apparent affinity for oleoyl-CoA was slightly increased with the mutations Ala122 and Gln122 such that oleoyl-CoA rather than oleate became the preferred ligand for these mutants. Small changes in protein stability were observed with the Arg122 mutations. The lack of notable ionic involvement of the conserved internal residue Arg122 in ligand binding is consistent with the hypothesis that the mode of ligand binding in liver fatty acid-binding protein is markedly different from that of other members of this lipid-binding protein family.

Acyl Coenzyme A↗
PubMed1994

The prevalence of hepatitis B and C in an antenatal population of various ethnic origins.

A total of 3522 samples of serum, collected anonymously from women attending an antenatal clinic, was tested for hepatitis B surface antigen and antibody to hepatitis C. The prevalence of anti-HCV was low; only five confirmed positives were found (0.14%). The prevalence of hepatitis B overall was 0.56%, but was 1.04% in women from immigrant groups. Hepatitis B carriage is therefore four times more common than hepatitis C carriage in the antenatal population comprised of various ethnic origins. The patterns of infection in the two viruses are reversed, hepatitis B being more common in Asian, S.E. Asian and West Indian mothers and hepatitis C being more common in mothers of white Caucasian origin. Routine antenatal screening for anti-HCV is discussed.

Adolescent↗
PubMed1994

Protracted venous infusion 5-fluorouracil and interferon-alpha in advanced and refractory colorectal cancer.

BACKGROUND: The management of patients with advanced colorectal cancer remains dependent on the optimal use of 5-Fluorouracil (5-FU). Enhanced 5-FU activity can be achieved by either adding a modulator or by altering the administration schedule, in particular using a protracted venous infusion. Based on encouraging phase II data using bolus 5-FU and interferon-alpha, we designed a study to investigate the activity of this modulator in patients with colorectal cancer refractory to protracted venous infusion 5-FU. PATIENTS AND METHODS: Patients with advanced colorectal cancer were treated with 5-FU (300 mg/m2/day) given as a protracted venous infusion via an indwelling central venous catheter and portable battery driven pump. At the time the tumour became refractory to 5-FU, interferon-alpha was added and further outcome evaluated. RESULTS: One hundred twenty-four patients were entered on the study, 118 of whom had measurable disease. Fifty-two patients had previously received chemotherapy. The overall tumour response rate with infusional 5-FU was 33% (38/118), however in previously untreated patients was 42% (29/69) and 18% in those given prior chemotherapy (9/49). At the point of refractory disease 64 patients had interferon-alpha added to the 5-FU. Five patients (8%) showed an objective partial response following interferon-alpha addition. Patient toxicities on infusional 5-FU included hand-foot erythroderma, stomatitis and diarrhoea. There were only 15 episodes of grade 3 or 4 toxicity. The addition of interferon-alpha gave fever, lethargy, myelosuppression and depression, but did not increase the incidence or severity of 5-FU related toxicities. Of 67 patients with tumour related pain, 53 (79%) had an improvement in their symptoms. Median survival of the whole group was 7.5 months. CONCLUSIONS: Protracted venous infusion 5-FU is an active and well tolerated palliative treatment for advanced colorectal cancer. The addition of interferon-alpha at the point of 5-FU refractory disease resulted in further significant response in a small number of patients. Further randomised studies, including quality-of-life end-points, are needed before the use of interferon-alpha can be recommended as a modulator of 5-FU in the clinical setting.

Adult↗
PubMed1994

Contact dermatitis from the old formula E45 cream.

In the past 4 years, a high incidence (118/362) of positive patch test reactions to E45 cream were noted in 2 patch testing clinics. 18/54 of those patch tested to all the ingredients demonstrated allergies to ingredients. The most frequent was triethanolamine; lanolin allergy occurring in only 1 patient. The remaining reactions may be explained as irritant reactions resulting from triethanolamine stearate (TES) formation within the cream. The irritancy of triethanolamine stearate was demonstrated in patients and controls. Conductivity studies showed that TES arises from the combination of the ingredients triethanolamine and stearic acid. The formulation of E45 cream was being changed at the time of writing, with the removal of triethanolamine from the product.

Chemistry, Pharmaceutical↗
PubMed1994

Analysis of delta-opioid receptor activities stably expressed in CHO cell lines: function of receptor density?

The question of whether short- and long-term opioid agonist activities could be affected by receptor density is being addressed with Chinese hamster ovary (CHO) cell lines stably expressing delta-opioid receptors. CHO cells expressing different levels of delta-opioid binding sites were isolated and characterized. The opioid binding sites in these cell lines have stereoselective high affinity for 3H-diprenorphine (0.18 to 0.91 nM), with agonist binding sensitive to both Na+ and GTP gamma S, and are of the delta-2-opioid receptor subtype. This is conclude from observations that the delta-2-opioid receptor-selective agonist naltriben (NTB) has higher affinity than the delta-1-opioid receptor-selective agonist 7-benzylidenenaltrexone (BNTX). It also could be demonstrated that delta-opioid agonists inhibited forskolin-stimulated intracellular 3H-cAMP production and that agonist inhibition could be blocked by pretreating cells with pertussis toxin. Again, NTB is more potent than BNTX or naloxone in reversing DPDPE inhibition of intracellular 3H-cAMP production. When the ability of [D-Ala2,D-Leu5]enkephalin (DADLE) to regulate adenylyl cyclase activity was examined in three separate CHO cell lines: CHODORX1-15, CHODORX1-8 and CHODORX1-4, which express 1.42 +/- 0.08, 0.74 +/- 0.07 and 0.27 +/- 0.04 pmol/mg-protein of receptor, respectively, maximal inhibitory levels in clones X1-15 and X1-8 were similar, whereas maximal inhibitory level for clone X1-4 was 66% of the other two clones. However, when maximal inhibitory levels of other opioid receptor-selective agonists were examined, different levels of inhibition were observed among these three CHO clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1994

Electrical properties of mammalian lens epithelial gap junction channels.

PURPOSE: To establish an "electrical fingerprint" for the gap junction channels between mammalian lens epithelial cells. METHODS: The double whole cell patch clamp technique was applied to isolated cell pairs obtained from mouse lens epithelium and a continuous cell line of lens epithelial cells derived from the sheep lens (SLE 2.1). RESULTS: The junctional conductance in mouse lens epithelial cells and in cultured SLE 2.1 cells was found to be moderately voltage dependent. SLE 2.1 cells were analyzed in more detail. The voltage dependence could be described by a Boltzmann distribution with Vo = +/- 63.1 mV and Gmin = 0.34. In cell pairs that exhibited spontaneously low junctional conductance, single channel events could be distinguished. Single gap junction channel currents had a linear current-voltage relationship. A frequency histogram of single channel conductances from eight cell pairs had three major peaks of 35, 60 and 97 pS. CONCLUSION: The electrical properties of gap junction channels between mammalian lens epithelial cells were virtually identical to those previously reported for transfected cell lines expressing connexin43. The authors' physiological data are therefore in agreement with molecular studies that have identified connexin43 as the major connexin of lens epithelial cells.

Animals↗
PubMed1993

Body Shape Questionnaire: derivation of shortened "alternate forms".

The 34-item Body Shape Questionnaire (BSQ) has demonstrated sound psychometric properties in all samples reported to date (including this study). However, the unidimensional nature of the 34 items suggests that the BSQ may be unnecessarily long for use in studies when body disparagement is not the main focus of investigation. This study of 342 adult women presents two 16-item "alternate forms" of the BSQ which showed equivalent means and excellent internal consistency in both derivation and replication samples. Two 8-item scales were also derived. The 34-, 16-, and 8-item versions showed equivalent convergent and discriminant validation against the Eating Attitudes Test (EAT)-26 and other parameters. We suggest that use of these 16-item versions may be more efficient than the original BSQ where body disparagement is not the sole focus of a study, or where a repeated measures design is employed. Furthermore, the 8-item versions are sufficiently robust to be used as "alternate forms" where speed of completion and economy are of the essence.

Adult↗