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Biomedical subjects

A Cooper

Publications and source records attributed to A Cooper.

At least 109 records · Page 6Linked to original sources
PubMed1999

A randomised comparison of the effects of oral versus transdermal 17beta-oestradiol, each combined with sequential oral norethisterone acetate, on serum lipoprotein levels.

OBJECTIVE: To investigate the effects of oral versus transdermal 17beta-oestradiol, given in both cases with sequential addition of oral norethisterone acetate, on serum lipid and lipoprotein levels in postmenopausal women. DESIGN: Open, randomised, parallel groups study. SETTING: University Clinical Research Group. POPULATION: Sixty-four postmenopausal women with climacteric complaints who were otherwise healthy were screened. Of these, 58 fulfilled the entry criteria. METHODS: Fifty-eight postmenopausal women were randomised to receive either oral 17beta-oestradiol/oestriol (Trisequens) or transdermal 17beta-oestradiol (Estrapak) together with cyclical addition of norethisterone acetate for 48 weeks. MAIN OUTCOME MEASURES: Serum levels of total cholesterol, triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL), very low density lipoproteins (VLDL), apolipoproteins, and lipoprotein(a) at baseline, and after 46 weeks (oestrogen-alone phase), and 48 weeks (oestrogen-progestogen phase) of treatment. RESULTS: Oral oestradiol therapy did not affect serum total cholesterol levels during the oestrogen-alone phase, but during the combined phase there was a 5% fall (P < 0.05) due to a 7% decrease in LDL cholesterol levels (P < 0.01). Oral therapy also increased serum triglyceride levels by 9.4% during the oestrogen-alone phase (P < 0.05). During the combined phase of transdermal therapy, there was a 19% fall in serum triglyceride levels (P < 0.05) and a 6% fall in HDL levels (P < 0.05). Oral oestradiol reduced lipoprotein(a) levels by 31% during the oestrogen-alone phase and by 37% with norethisterone acetate addition (P < 0.05). Transdermal therapy had no significant effect on lipoprotein(a). CONCLUSIONS: Other than a minor fall in HDL3 in women receiving transdermal 17beta-oestradiol, coadministration of oral progestogen in general improved, rather than worsened, this serum lipoprotein profile.

Administration, Cutaneous↗
PubMed1999

Why patients do not attend cardiac rehabilitation: role of intentions and illness beliefs.

OBJECTIVE: Many patients fail to attend cardiac rehabilitation. Attempts to identify sociodemographic or clinical predictors of non-attendance have not been very successful; therfore, this study aimed to determine whether the illness beliefs held during hospitalisation by patients who had suffered acute myocardial infarction or who had undergone coronary artery bypass graft surgery could predict cardiac rehabilitation attendance. SUBJECTS AND METHODS: 152 patients were prospectively studied of whom 41% had attended cardiac rehabilitation at six months. RESULTS: In addition to being older, less aware of their cholesterol values, and less likely to be employed, non-attenders were less likely to believe their condition was controllable and that their lifestyle may have contributed to their illness. CONCLUSION: It should now be determined whether interventions aimed at optimising certain perceptions could promote cardiac rehabilitation uptake among those patients who could benefit the most.

Age Factors↗
PubMed1999

Effect of a microwave coagulator on implanted liver neoplasms in rats.

An experimental study was conducted to determine the applicability of a microwave (MW) source for coagulation and dissection of metastatic tumour and liver parenchyma. Twenty PVG rats were studied after implantation of MC28 tumour cells into the liver. Eleven days later they underwent sham laparotomy (control) MW coagulation of the tumour deposit, local resection of the tumour deposit with 2 mm clearance or resection of the tumour with MW coagulation of the resection zone. The control animals all died with blood-stained ascites and heavy tumour burden in the liver. After MW coagulation, tumours disappeared in all but one rat. Local resection also led to tumour clearance in 4 of 5 rats. MW coagulation of the resection zone allowed rapid bloodless resection, and no tumour recurrence was observed after 40-89 days. We conclude that MW coagulation is a potentially useful tool for ablation of hepatic metastasis and as an adjunct to hepatic resection.

Animals↗
PubMed1999

Novel classes of fatty acid and retinol binding protein from nematodes.

Parasitic nematodes have recently been found to produce proteins which represent two new classes of fatty acid and retinoid binding protein. The first is the nematode polyprotein allergens/antigens (NPAs) which, as their name suggests, are synthesised as large polyproteins which are subsequently cleaved at regularly spaced sites to form multiple copies of a fatty acid binding protein of approximately 14.5 kDa. Binding studies using molecular environment-sensitive fluorescent ligands have shown that the binding site is highly unusual, producing blue-shifting in fluorescence to an unprecedented degree, suggesting a remarkably non-polar environment and isolation from solvent water. Computer-based structural predictions and biophysical observations have identified the NPAs as highly helical proteins which might form a four helix bundle, so constitute a new class of lipid binding protein from animals. The second class, like the NPAs, binds both fatty acids and retinol, but with a higher affinity for the latter. These are also highly helical but are structurally distinct from the NPAs. The biological function of these new classes of protein are discussed in the context of both the metabolic requirements of the parasites and the possible role of the proteins in control of the immune and inflammatory environment of the tissue sites parasitised.

Animals↗
PubMed1999

Prolactin response to the severity of surgical insult.

Prolactin levels are elevated significantly during the recovery process from surgical insult, implying a role for prolactin in the neuroendocrine immune network. This study examined the importance of severity of surgical insult to the prolactin response. Two groups of surgical patients were chosen consecutively and studied prospectively. Seven patients scheduled for "clean" elective surgery, i.e., herniorrhaphy and laparoscopic cholecystectomy, were compared with seven patients scheduled for prolonged abdominal exploration. Blood was drawn for prolactin and cortisol at 8:00 AM on the day of surgery and on postoperative days one, three, and five. Using a two-tailed test, preoperative prolactin levels and levels on postoperative days three and five were significantly different in the prolonged surgery group (.012 and .002, respectively). There were no statistically significant differences in preoperative and postoperative prolactin levels in the clean surgery group. Cortisol levels were not significantly elevated in either group. These results indicate that the prolactin response to surgery is related to the severity of the surgical insult.

Case-Control Studies↗
PubMed1998

Testing the Cambrian explosion hypothesis by using a molecular dating technique.

Molecular studies have the potential to shed light on the origin of the animal phyla by providing independent estimates of the divergence times, but have been criticized for failing to account adequately for variation in rate of evolution. A method of dating divergence times from molecular data addresses the criticisms of earlier studies and provides more realistic, but wider, confidence intervals. The data are not compatible with the Cambrian explosion hypothesis as an explanation for the origin of metazoan phyla, and provide additional support for an extended period of Precambrian metazoan diversification.

Animals↗
PubMed1998

A common mitochondrial DNA variant is associated with insulin resistance in adult life.

Mitochondrial DNA is maternally inherited. Mitochondrial DNA mutations could contribute to the excess of maternal over paternal inheritance of non-insulin-dependent diabetes mellitus (NIDDM). We therefore investigated the relationship between this variant, insulin resistance and other risk factors in a cohort which had been well characterised with respect to diabetes. Blood DNA was screened from 251 men born in Hertfordshire 1920-1930 in whom an earlier cohort study had shown that glucose tolerance was inversely related to birthweight. The 16189 variant (T--> C transition) in the first hypervariable region of mitochondrial DNA was detected using the polymerase chain reaction and restriction digestion. DNA analysis showed that 28 of the 251 men (11%) had the 16189 variant. The prevalence of the 16189 variant increased progressively with fasting insulin concentration (p < 0.01). The association was independent of age and body mass index and was present after exclusion of the patients with NIDDM or impaired glucose tolerance. We found that insulin resistance in adult life was associated with the 16189 variant. This study provides the first evidence that a frequent mitochondrial variant may contribute to the phenotype in patients with a common multifactorial disorder.

Adult↗
PubMed1998

Preventing hypothermia: convective and intravenous fluid warming versus convective warming alone.

STUDY OBJECTIVE: To test the hypothesis that warming intravenous (i.v.) fluids in conjunction with convective warming results in less intraoperative hypothermia (core temperature < 36.0 degrees C) than that seen with convective warming alone. DESIGN: Prospective, randomized study. SETTING: University affiliated tertiary care teaching hospital. PATIENTS: 61 ASA physical status, I, II, and III adults undergoing major surgery and general anesthesia with isoflurane. INTERVENTIONS: All patients received convective warming. Group 1 patients received warmed fluids (setpoint 42 degrees C). Group 2 patients received room temperature fluids (approximately 21 degrees C). MEASUREMENTS AND MAIN RESULTS: Lowest and final intraoperative distal esophageal temperatures were higher (p < 0.05) in Group 1 (mean +/- SEM: 35.8 +/- 0.1 degrees C and 36.6 +/- 0.1 degrees C) versus Group 2 (35.4 +/- 0.1 degrees C and 36.1 +/- 0.1 degrees C, respectively). Compared with Group 1, more Group 2 patients were hypothermic at the end of anesthesia (10 of 26 patients, or 38.5% vs. 4 of 30 patients, or 13%; p < 0.05). After 30 minutes in the recovery room, there were no differences in temperature between groups (36.7 +/- 0.1 degrees C and 36.5 +/- 0.1 degrees C in Groups 1 and 2, respectively). Intraoperative cessation of convective warming because of core temperature greater than 37 degrees C was required in 33% of Group 1 patients (vs. 11.5% in Group 2; p = 0.052). CONCLUSIONS: The combination of convective and fluid warming was associated with a decreased likelihood of patients leaving the operating room hypothermic. However, average final temperatures were greater than 36 degrees C in both groups, and intergroup differences were small. Care must be taken to avoid overheating the patient when both warming modalities are employed together.

Adult↗
PubMed1998

New uses for old DNA.

Several years have elapsed since the last report of million-year-old DNA, coinciding with increased standards for experimental procedures in ancient DNA research. Whereas many earlier studies are now regarded as erroneous, the recent successful characterisation of Neanderthal DNA has set new standards for the field. Researchers continue to find new ways to exploit preserved genetic information in studies of more recent remains, widening the utility of ancient DNA.

Animals↗
PubMed1998

Growth inhibitory effect of lithium gammalinolenate on pancreatic cancer cell lines: the influence of albumin and iron.

Essential fatty acids, especially gamma linolenic (GLA) and eicosapentaenoic acids, have been proposed as potential anticancer drugs. Our aim was to study the effect of the lithium salt of gamma linolenic acid (LiGLA) on the growth of two human pancreatic cancer cell lines (MIA PaCa2 and Panc 1) and primary human fibroblasts (HFF 5) in vitro. Cell growth was assessed by a microculture tetrazolium (MTT) assay. LiGLA had a selective growth inhibitory effect on pancreatic cancer cell lines with 50% growth inhibition (IC50) at approximately 6-16 mumol/l compared with approximately 111 mumol/l for the fibroblasts. The degree of growth inhibition increased with the time of exposure to LiGLA. Special attention was paid to the influence of albumin and iron on LiGLA-mediated growth inhibition. Albumin incorporated into essentially serum-free culture medium inhibited the effect of LiGLA in a dose-dependent manner, associated with reduced GLA uptake by cancer cells. Ferric ions were confirmed as potentiators of the growth inhibitory effect of LiGLA but more physiologically relevant transferrin-bound iron was ineffective. With further improvements in the fatty acid delivery mechanism, LiGLA may become a useful adjunct in the management of pancreatic cancer patients.

Albumins↗
PubMed1998

Effect of lithium gamma-linolenate on the growth of experimental human pancreatic carcinoma.

BACKGROUND: The lithium salt of gamma-linolenic acid (Li-GLA) is growth inhibitory to pancreatic cancer cells in vitro and is reported to prolong the survival of patients with pancreatic cancer. The effect of Li-GLA on the growth of human pancreatic carcinoma in vivo is not known. In this study the effect of parenterally administered Li-GLA on the growth of human pancreatic carcinoma in nude mice was tested. METHODS: Pancreatic tumours were produced in nude mice by subcutaneous implantation of MIA PaCa-2 cells. This cell line is sensitive to Li-GLA in vitro. Mice were randomly treated with intraperitoneal, intravenous or intratumoral Li-GLA. Each group also had controls. RESULTS: Both intravenous and intraperitoneal administration of Li-GLA had no significant effect on tumour growth or tumour phospholipid fatty acid composition. Intratumoral administration of Li-GLA was, however, associated with a significant antitumour effect. CONCLUSION: Within the limitations of this tumour model, the benefit seen with intravenous Li-GLA in patients with pancreatic carcinoma cannot be explained by tumour growth inhibition. Local administration appears to be more effective than intravenous or intraperitoneal therapy.

Animals↗
PubMed1998

Discovery of critical Tol A-binding residues in the bactericidal toxin colicin N: a biophysical approach.

Colicins translocate across the Escherichia coli outer membrane and periplasm by interacting with several receptors. After first binding to outer membrane surface receptors via their central region, they interact with TolA or TonB proteins via their N-terminal regions. Finally, the toxic C-terminal region is inserted into or across the cytoplasmic membrane. We have measured the binding of colicin N to TolA by isothermal titration microcalorimetry (ITC) and tryptophan fluorescence. The isolated N-terminal domain exhibits a higher affinity for TolA (Kd = 1 microM) than does the whole colicin (18 microM), and similar behaviour has been observed when the N-terminal domain of the g3p protein of the bacteriophage fd, which also binds TolA, is examined in isolation and in situ. This may indicate a similar mechanism in which a cryptic TolA binding site is revealed after primary receptor binding. The isolated colicin N N-terminal domain appears to be unstructured in circular dichroism and fluorescence studies. We have used mutagenesis and ITC to characterize the TolA binding site and have shown it to be of a different sequence and much further from the N-terminus than previously thought.

Amino Acid Sequence↗
PubMed1998

Differential effects of cryopreservation on nuclear or cytoplasmic maturation in vitro in immature mouse oocytes from stimulated ovaries.

The aim of this study was to develop a maturation protocol for immature oocytes and assess the protocol with cryopreserved oocytes. Nuclear maturation (mature spindle and aligned chromosomes) occurred irrespective of the treatment regime: 71-89% of oocytes matured in vitro had a normal spindle and chromosomes compared with 87% matured in vivo. Fertilization rates were not significantly different from those of in-vivo matured oocytes. Of the maturation treatment regimes investigated, the initial treatment producing best development to blastocyst (cytoplasmic maturation) involved a 2 h incubation in standard maturation medium (SMM) containing 7.5 IU follicle stimulating hormone (FSH) followed by 14 h in SMM plus 7.5 IU FSH:luteinizing hormone with follicular cells [62% (range 49-69)]. The addition of 1 ng/ml epidermal growth factor (EGF) in this protocol resulted in development [75% (range 71-81)] that was not significantly different from in-vivo matured oocytes [82% (range 73-90)]. Exposure of the oocytes to 1.5 M dimethylsulphoxide (DMSO) did not affect fertilization or development rates. Following a slow-cool/thaw freezing regime, 81% (range 74-89) of the oocytes were morphologically normal, i.e. had a spherical shape with an intact zona and oolemma; they had, however, lost their previously attached cumulus and corona cells. Maturation of frozen-thawed oocytes in the presence of EGF gave good fertilization rates but poor development rates [80% (range 77-86) and 37% (range 33-40) respectively]. In conclusion, the best maturation, both nuclear and cytoplasmic, occurred in the presence of a combination of gonadotrophins, EGF and follicular cells. Oocytes cryopreserved using a slow-cool/thaw regime can be matured to produce blastocysts after in-vitro fertilization.

Animals↗