A rapid and inexpensive method for the addition of poly A coding tracts to transcription vectors.
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Genetic Vectors↗
Biomedical subjects
D Sullivan
Publications and source records attributed to D Sullivan.
Tumour evolution in rats monitored by changes to serum and lipoproteins.
The biochemical, physicochemical and magnetic resonance (MR) properties of rat serum allow tumour evolution to be monitored. Serum from female Fischer rats injected with rat mammary adenocarcinoma cells contained a low-density lipoprotein (LDL)-like lipoprotein and decreased high-density lipoprotein levels compared with normal rat serum. Increases in secondary tumour burden coincided with enlarged LDL-like particles, altered MR properties and elevation of serum triglyceride. By fucosidase treating metastatic R13762 cells prior to injection, not only was metastatic capacity retarded, but serum lipoproteins were also altered. These physicochemical alterations suggest an intricate relationship between both primary and secondary tumour burdens and the serum lipoprotein profile.
Adenocarcinoma↗
Combination fixed/removable implant prosthetics using spark erosion technology.
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Denture Design↗
Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.
The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.
Adult↗
Assay of apolipoproteins A-1 and B by immunoturbidimetry: detection of individuals at risk for atherosclerotic artery disease.
Recent evidence has suggested that the levels of Apolipoprotein A-1 and B in plasma are better indicators of the risk of atherosclerotic artery disease than plasma lipids. This study describes the measurement of plasma Apolipoprotein A-1 and B by immunoturbidimetry in patients with atherosclerotic artery disease and in normal controls. Apoprotein B and the ratio of Apoprotein A-1/Apoprotein B were found to be the best discriminators between the two groups.
Adult↗
Determinants of pulmonary function in patients undergoing coronary bypass operations.
Pulmonary function testing was conducted consecutively in 29 healthy men (age range, 42 to 71 years) undergoing elective coronary artery bypass grafting. Lung volumes, expiratory flow rates, diffusing capacity, and blood gases were determined before operation, at discharge (8.7 +/- 1.9 days), and at 3 months postoperatively. In addition, peak expiratory flow rate was measured immediately after extubation (21.4 +/- 2.7 hours). Fifteen patients had smoked within the past year, but none had a history of pulmonary impairment. Twenty-two patients had internal mammary artery (IMA) dissection. Operation and recovery were uneventful in all cases. After extubation, peak expiratory flow rate was decreased by 65%. At discharge, lung volumes were decreased by 19% to 33% below preoperative values and expiratory flow rates were decreased by 33% to 37% below preoperative values. Some minor changes were detected at 3 months. Further analysis of these changes according to smoking history, age, preoperative weight, dissection of IMA, and aortic cross-clamp time showed that only IMA dissection affected the postextubation changes in peak expiratory flow rate (p less than 0.0001), whereas the decreases in functional residual capacity and expiratory reserve volume at discharge were affected by IMA dissection (p less than 0.05) and age (p = 0.01). Thus, median sternotomy is associated with severe but short-term pulmonary dysfunction; IMA dissection has a significant adverse effect on these changes.
Age Factors↗
Acute effects of intravenous cyclosporine on blood pressure, renal hemodynamics, and urine prostaglandin production of healthy humans.
The acute renal failure associated with cyclosporine may result from vasoconstriction of intrarenal arterioles. To evaluate the mechanism of cyclosporine-induced nephrotoxicity, we acutely administered cyclosporine to eight healthy female volunteers with normal blood pressure and renal function. Cyclosporine (4 mg/kg) in 250 ml of 5% dextrose in water (D5W) was administered as a steady intravenous infusion over 6 hr. Glomerular filtration rate and renal plasma flow were measured by serum disappearance of 99m TcDTPA and 131I hippuran, respectively, during the last 3 hr of the infusion. D5W was given to the patients on separate days before the cyclosporine infusion to obtain control data. Systolic and diastolic blood pressure measured every hour during the infusions and renal vascular resistance were slightly higher during cyclosporine administration, but the increases were not statistically significant. Renal plasma flow was not affected by cyclosporine, being 479.6 +/- 24.9 ml/min during the control infusion and 463.3 +/- 12.7 ml/min during the cyclosporine infusion. However, glomerular filtration rate was reduced by cyclosporine in all patients (control, 108.8 +/- 2.5 ml/min, vs. cyclosporine, 91.1 +/- 2.2 ml/min, P less than .01), except one who demonstrated no significant change. Urinary excretion of thromboxane B2 during cyclosporine administration was markedly increased in all patients, being 39.9 +/- 8.2 ng/hr in the control period and 85.8 +/- 22.3 ng/hr during cyclosporine infusion (P less than .05), except for the one patient in whom no decrease in GFR was noted. There was no significant change in the urinary excretion rate for 6-keto-prostaglandin F1a or prostaglandin E during cyclosporine infusion. Serum averaged levels of peripheral renin activity, angiotensin II, and aldosterone did not change during with the cyclosporine administration compared with the control. All patients demonstrated a decrease in 24-h urinary excretion of sodium and potassium on the day of the cyclosporine infusion. Verapamil SR (240 mg daily for 7 days prior to cyclosporine infusion) did not reverse the reduction in glomerular filtration rate induced by cyclosporine; however, a significant reduction in renal vascular resistance and an increase in renal plasma flow (P less than .05) were noted when the volunteers were treated with both verapamil and cyclosporine compared with cyclosporine alone. Intravenous infusion of Cremophor EL, the vehicle to dissolve cyclosporine, demonstrated no significant effects on blood pressure, renal hemodynamics or urinary prostaglandin excretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Cocaine and lidocaine interfere with epinephrine-induced changes in intracellular calcium concentration and glucose efflux from rat hepatocytes.
The mechanism of cocaine-induced hepatotoxicity is not clearly understood. Recent studies show that fluctuations in intracellular Ca2+ ([Ca2+]i) and/or cyclic-AMP ([cAMP]) concentration play a major role in hormone action, and sustained elevations in [Ca2+]i may be involved in the initiation of hepatocellular damage. To evaluate the possible involvement of intracellular Ca2+ and/or cAMP, we investigated effects of cocaine and lidocaine on basal, epinephrine and dibutyryl cyclic-AMP (DBcAMP)-induced changes in [Ca2+]i and glucose efflux from isolated rat hepatocytes. [Ca2+]i was monitored continuously using a Ca2(+)-selective fluorescence indicator, Quin-2, and was calculated after correcting for autofluorescence. Neither cocaine nor lidocaine (0.1-5 mmol/l) affected basal [Ca2+]i, yet both agents decreased epinephrine (10 mumol/l) and DBcAMP (100 mumol/l)-induced increases in [Ca2+]i in a dose-dependent fashion. Half-maximal inhibition occurred at 0.75 mmol/l cocaine and 1.7 mmol/l lidocaine. Cocaine and lidocaine also decreased epinephrine and DBcAMP-induced glucose efflux. The dose-dependent effect on epinephrine-induced glucose efflux was similar to that of both anesthetics on epinephrine-induced increases in [Ca2+]i. However, 5 mmol/l cocaine or lidocaine decreased DBcAMP-induced glucose efflux by less than 50%, and [Ca2+]i by more than 80%. Taken together, these results indicate that cocaine and lidocaine decrease the ability of epinephrine to stimulate glucose efflux by interfering with the Ca2(+)-mediated, and not the cAMP-mediated intracellular pathway. It is therefore speculated that alterations in metabolic endocrine regulation may contribute to cocaine's hepatotoxic effect.
Animals↗
Hepatic fibrosis with the use of methotrexate for juvenile rheumatoid arthritis.
Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. One complication of MTX is hepatotoxicity. Although liver function tests may be abnormal with its use, in this setting they do not correlate well with the development of hepatic fibrosis. Periodic liver biopsy is required to monitor for the hepatotoxic changes secondary to MTX. We describe and discuss the case of a 17-year-old woman who developed evidence of hepatic fibrosis after 3 years of MTX therapy.
Adolescent↗
Efficacy of prophylactic antibiotics in vascular surgery: an arterial wall microbiologic and pharmacokinetic perspective.
This prospective study examined microbiologic features of arterial tissue and pharmacokinetics and bioactivity of cefamandole and cefazolin in patients undergoing elective primary prosthetic aortoiliofemoral/infrainguinal reconstruction. Double-blind, randomized, perioperative prophylaxis (1 gm intravenously every 6 hours for nine doses) with cefamandole or cefazolin was administered to 47 patients. Specimens of blood serum, subcutaneous fat, thrombus, atheroma, and arterial wall were obtained for culture and minimal inhibitory concentration and drug level analysis by high-pressure liquid chromatography. The serum half-life (hr +/- SEM) was 1.43 +/- 0.36 for cefamandole and 2.22 +/- 0.40 for cefazolin. Over the first 2 hours of surgery and for all time intervals combined, the serum concentration of cefazolin was significantly higher (p less than 0.025) than cefamandole. Irrespective of sampling time, the tissue concentration of cefazolin was significantly greater (p less than 0.005) than cefamandole. Positive arterial tissue cultures were obtained in 12 of 29 patients (41.4%) from 23 of 116 (19.8%) arterial tissue specimens. Coagulase-negative Staphylococcus was the predominant isolate, 64 of 93 (68.8%). Twenty-five of the 51 coagulase-negative staphylocci tested (49%) were slime-producers. During surgery, the arterial tissue concentration of cefamandole fell below the geometric mean minimal inhibitory concentration against all organisms combined, and against S. aureus (with the highest minimal inhibitory concentration of the prevalent isolates), significantly more often than the concentration of cefazolin. The data show that a significant number of primary elective aortoiliofemoral/infrainguinal reconstructions are associated with positive arterial tissue cultures, which represent a potential source of graft infection.(ABSTRACT TRUNCATED AT 250 WORDS)
Arteries↗
Effect of thermal injury in the rat on transfer of IgA protein into bile.
Severe thermal injury is associated with bacterial sepsis; the intestine is considered a likely source of invasive organisms. Because IgA antibody in bile accounts for much of the specific immune defense of the upper intestinal tract in the rat, the effect of thermal injury on the quantity of IgA protein in bile was examined. Sprague-Dawley rats received a 20% to 30% body surface area burn under anesthesia. Eighteen hours later the common bile duct was cannulated and bile was collected for three hours. Total IgA protein in bile decreased 90% after thermal injury. The bile volume, the concentration of bile protein, and free secretory component did not change significantly. Although blood flow to the liver 18 hours after thermal injury was not changed, there was a significant reduction in total IgA concentration in the circulation; both monomeric (m-IgA) and polymeric IgA (p-IgA) were decreased. This finding may explain, in part, the reduced concentration of IgA protein in bile. Although not examined in this study, decreased local hepatic synthesis and/or transport of p-IgA across the hepatocyte may also contribute to the reduced IgA levels in bile.
Animals↗
Acute effects of intravenous cyclosporine on renal function in healthy humans.
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Adult↗
Hyperlipidemia as a biochemical basis of magnetic resonance plasma test for cancer.
An increase in the plasma levels of apoprotein B-containing lipoproteins is the basis of the magnetic resonance (MR) test for cancer. The narrow MR line width reported by Fossel and co-workers to be associated with the presence of malignant disease is due to a relative increase of very low density lipoprotein. In contrast, the plasma from healthy controls, which has a much broader spectrum, has a higher proportion of high density lipoprotein. However, plasma from patients with hyperlipidemia unrelated to cancer also show narrow MR line widths and are therefore a confounding variable. We used magnetic resonance spectroscopy (MRS) to assess the plasma from 253 patients with a range of lipid related diseases and cancer, and 28 controls. A significant difference (p less than or equal to 0.0005) of 10 Hz exists between the mean line width of the controls and hyperlipidemics without malignant disease. However, in patients with solid tumours a difference of 7 Hz (p less than or equal to 0.0005) in the mean values is recorded although there is an overlap of 6 Hz compared with the controls. Moreover the MRS method was not found to distinguish patients with lymphomas from the control population. The index was not found to be related to patient age or tumour burden.
Adult↗
Opportunistic health promotion: do patients like it?
In a five doctor general practice 100 adults attending routine surgeries were given questionnaires to assess the influence of discussing health promotion on their satisfaction with the consultation. Health promotion topics were discussed in 74% of the 86 consultations analysed. Of these consultations, blood pressure was mentioned in the largest number (48%) and breast self-examination in the smallest (6%). Patient satisfaction was not significantly influenced by the inclusion or omission of such topics. The highest mean satisfaction score was for those discussing smoking and the lowest for those discussing alcohol. Most patients (84%) found discussion of health promotion helpful and felt comfortable (62%); only two patients felt uncomfortable doing so.
Adolescent↗
The Nucleic Acid Blot Analyzer II. ANALYZE, an image analysis software package for molecular biology.
The Nucleic Acid Blot Analyzer, a new instrument providing high-speed imaging of 32P labeled nucleic acids, captures, stores and presents images in digital form, thus lending itself to rapid data handling and analysis as well as replacing conventional X-ray film autoradiography for many applications. A software package called ANALYZE has been specifically designed for the instrument in order to provide automatic or semi-automatic analysis for molecular biological techniques. The software includes image display manipulation, quantitative and positional analysis, as well as file maintenance utilities. The specific application of the software/hardware to various techniques is presented.
Molecular Biology↗
A continuing education program for nurse practitioners in ambulatory care.
Continuing education should be an integral part of all health care providers' practice. This article discusses the recognition of this need by a group of nurse practitioners in an acute ambulatory care center. The process undertaken in developing the program of continuing education is described. The program outline can serve as a model for other NPs in similar settings.
Ambulatory Care↗
Gross cystic disease of the breast.
The aetiology of fibrocystic disease of the human breast remains problematical. While oestrogens may cause cystic lesions and epithelial proliferation in the mammary glands of experimental animals and certain progestogens (chlormadinone acetate and medroxyprogesterone acetate) may induce severe myoepithelial hyperplasia in beagles, the classical oral contraceptives (oestrogens and progestogens) reduce the incidence of fibrocystic breast disease in women. The role of prolactin in human breast disease is far from clear despite the fact that in rodents mammary tumors fail to develop following oestrogen administration in the absence of prolactin. Because women with gross cystic disease of the breast are at four times greater risk of developing malignant breast disease, it is felt that the administration of courses of danazol, an impeded androgen derived from the progestin, 17 alpha-ethinyl testosterone, has proved effective in lessening fibrocystic disease of the breast, frequently obviating the need for breast biopsy. The study of the hormonal content of fluid aspirated from gross breast cysts should help elucidate the pathophysiology of breast disease. Breast cyst fluid is rich in androgens, particularly dehydroepiandrosterone sulfate; concentrations of polypeptide hormones like FSH, LH, TSH, PRL, and calcitonin are invariably present sometimes in less and at other times in greater amounts than that found in plasma. Of particular interest is the finding of measurable levels of beta-hCG in cyst fluid but not in the serum. The question arises whether the beta-hCG is biologically active or are the assay values merely the expression of radioimmunoassayable components? Preliminary (as yet unpublished) studies reveal excellent bioactivity as measured by testosterone production in Leydig cell cultures. Time will tell whether elevated levels of bioactive beta-hCG portend neoplastic potential.
Aged↗
Alpha-2-adrenergic control of prolactin release.
The role of the alpha 2-adrenergic system in regulating prolactin release has been studied in vivo in male rats. Yohimbine administration alone, at doses ranging from 0.2 to 5.0 mg/kg, resulted in a dose-related elevation of plasma prolactin levels from a basal level of 8 +/- 2 to 65 +/- 6 ng/ml at the highest dose. In the same experiment clonidine, 0.2 mg/kg, suppressed basal prolactin levels to 4 +/- 1 ng/ml and returned prolactin levels of all animals receiving 0.2-5.0 mg/kg yohimbine to basal levels. Rats were treated with increasing doses of clonidine (0.05-1.0 mg/kg) in the presence or absence of a constant dose (1.0 mg/kg) of yohimbine. Clonidine alone at doses of 0.05 and 0.2 mg/kg again significantly suppressed prolactin levels, while a dose of 1.0 mg/kg did not (failure of high dose clonidine to suppress prolactin levels suggests an additional effect of clonidine on prolactin secretion unrelated to alpha 2-adrenergic agonist action). All three doses of clonidine completely reversed yohimbine-induced prolactin release. Basal prolactin levels were also significantly reduced by the selective alpha 2-adrenergic agonist UK-14,304 at a dose of 0.2 mg/kg. Yohimbine-induced prolactin release was reversed by UK-14,304 at doses of 0.2 and 1.0 mg/kg, but not at the lowest dose studied, 0.05 mg/kg. The lower potency of UK-14,304 than clonidine in this assay is consistent with the lower potency of UK-14,304 as an alpha 2-adrenergic-agonist antihypertensive agent. Several alpha 2-antagonists in addition to yohimbine were studied.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗