Biomedical subjects
C Warren
Publications and source records attributed to C Warren.
Metabolic and hormonal responses to exercise in partially hepatectomised rats.
To characterise how the liver affects metabolic and hormonal exercise responses, hepatectomised (70%; HX) rats were submitted to a 30- or 50-min treadmill exercise (26 m/min, 0% slope) 48 hr or 7 days after surgery (reduced or normal liver mass, respectively). To determine whether metabolic effects of liver mass reduction during exercise were caused by reduced capacity of the liver to produce glucose, metabolic and hormonal responses to the same exercise protocol were measured in 48-hr HX rats. Euglycemia, maintained by exogenous glucose infusion, produced attenuated lactate, insulin, and glucagon values in 48-hr HX rats but did not affect FFA, glycerol, and plasma catecholamine responses. Results indicate that metabolic and hormonal exercise responses are amplified in 48-hr HX rats. Maintaining euglycemia in 48-hr HX rats during exercise does not reduce all responses. Intrahepatic events, similar to those in a short-term (48-hr) HX liver, may influence metabolic and hormonal exercise responses.
Effects of hepatic portal infusion of deionized water on metabolic and hormonal responses to exercise in rats.
The present study was conducted to investigate the in vivo effects of an intrahepatic infusion of deionized water during exercise in rats. Adrenodemedullated male Sprague-Dawley rats were continuously infused for 30 min either at rest or during treadmill exercise (26 m/min, 0% grade). Rats were randomly assigned to one of three infusion conditions (52 micro ul/min) with either deionized water (PW) or saline (PS; NaCl; 0.9%) via the hepatic portal vein or deionized water through the jugular vein (JW). The exercise period caused a significant (P < 0.05) decrease in liver glycogen and relative liver water content and peripheral and portal blood glucose and insulin while increasing peripheral and portal glucagon and K+ plasma concentrations. These responses, with the exception of K+, were not influenced by the different types of infusions. The increase in K+ during exercise was significantly (P < 0.05) higher in JW rats than in the PW and PS groups. Both the infusion and exercise protocols did not significantly alter the liver weight-to-body weight ratio, plasma osmolality, free fatty acids, beta-hydroxybutyrate, Na+, Cl-, vasopressin, and catecholamine concentrations. It is concluded that an hepatic portal infusion of deionized water does not specifically alter the metabolic and hormonal responses to exercise in rats.
Blood without tears.
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Lethal autonomy: the malfunction of the informed consent mechanism within the context of prenatal diagnosis of genetic variants.
In this article, Cara Dunne and Catherine Warren challenge the current role of genetic counselors in advising expectant mothers about potential genetic defects of their fetuses. They show that genetic counselors sometimes provide one-sided negative information to women undergoing prenatal diagnosis of genetic variants. This biased information promotes abortion of what are considered "defective" fetuses. The misleading information provided by the genetic counselors and the termination of the pregnancies is akin to the eugenics movement. The authors describe the early 20th century eugenics movement, explore the origin and development of the Human Genome Project, analyze the current role of genetic counseling, and explain the importance of the informed consent process to the exercise of autonomy. Dunne and Warren conclude by offering methods by which to restructure the informed consent mechanism to offer a more balanced assessment of the risks and benefits associated with genetic disability.
Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions.
Results from the 1995 National College Health Risk Behavior Survey.
Results from the 1995 National College Health Risk Behavior Survey, which monitored health risk behaviors among US college and university undergraduates, suggest that many students' behaviors increase their likelihood of adverse health outcomes. During the 30 days preceding the survey, 34% of the participants had consumed five or more alcoholic drinks on at least one occasion, and 27% had drunk alcohol and driven a car. Thirty-one percent had smoked cigarettes regularly during their lifetimes, 49% had ever used marijuana, 30% had used a condom during their last sexual intercourse, 21% were overweight, and 38% had participated in vigorous physical activity on 3 or more of the 7 days preceding the survey. These data were analyzed by gender, age group, race and ethnicity, and institution type. They can be used by those responsible for the health and education of college students to reduce risks associated with the leading causes of mortality and morbidity.
Beneficence toward whom? Ethical decision-making in a maternal-fetal conflict.
Ethical dilemmas and conflicts occur frequently in critical care units. When these dilemmas involve a pregnant patient, the conflicts are further complicated, because they also involve the interests of the fetus. Using an ethical decision-making process facilitates the analysis of ethical dilemmas and their resolutions. This process is used to analyze the dilemma of selecting appropriate treatment for a woman at 30 weeks' gestation, diagnosed with acute lymphocytic leukemia. The case is examined from the perspective of the mother and the fetus, using the decision-making process. The medical indications include the patient's physical state, disease process, and treatment options. Patient preferences are the ethical and legal center of the patient-physician, and patient-nurse relationship. Contextual features include religious beliefs, cultural values, family dynamics, and financial and legal aspects of the care options. Finally, the ethical principles, relevant and in conflict, are assessed. Exploring these areas clarifies the best treatment option in consideration of the issues and facts of the case.
Effects of dietary manipulations and glucose infusion on glucagon response during exercise in rats.
The purpose of the present investigation was to test the hypothesis that blood glucose concentration is not always related to glucagon response during exercise. Three groups of rats were submitted to a prolonged (3-h) swimming exercise. Two groups of rats had their normal food intake restricted by 50% the night before the experiment. One of these two groups of rats was intravenously infused with glucose throughout exercise to maintain euglycemia. The third group of rats swam while under normal dietary conditions. Plasma glucose, sampled in arterial blood, was reduced (P < 0.05) at 75, 105, 150, and 170 min of exercise (from approximately 130 to 110 mg/dl) in the food-restricted animals without glucose infusion, whereas a significant (P < 0.05) increase was measured in the two other groups during exercise. A significant (P < 0.01) difference in the mean integrated areas under the glucose-concentration curve was found only between the fed and the two food-restricted groups. Plasma insulin concentrations decreased (P < 0.05) similarly in all groups during exercise, whereas plasma epinephrine and norepinephrine concentrations increased significantly (P < 0.01) in all groups. Despite differences between groups in plasma glucose response during exercise, and despite the absence of any decrease in exercising blood glucose levels in at least two of the three groups, plasma glucagon responses were increased (P < 0.05) similarly in all groups (from approximately 250 to 550 pg/ml) at the end of the exercise period. The increase in glucagon was significant after 90 min of exercise in the food-restricted groups, with or without glucose infusion, but only after 140 min in the fed group. These results indicate that the glucagon response during exercise is not always linked to the decrease in plasma glucose.
The relationship between hyaluronidase activity and hyaluronic acid concentration in sera from normal controls and from patients with disseminated neoplasm.
Serum hyaluronidase activity (HAE) and hyaluronic acid (HA) concentration were measured in sera from patients with disseminated neoplasm and compared to those of normal controls. The serum HAE activity in disseminated neoplasm (mean, 12.6 mumol N-acetylglucosamine (NAG)/min/1; range, 5.2-24.7 mumol NAG/min/1) was significantly lower (t = 6.7, p < 0.001) than in normal controls (mean, 17.1 mumol NAG/min/1; range, 11.5-27.0 mumol NAG/min/1). The serum HA concentration in patients with disseminated neoplasm (mean, 8199.7 micrograms/l; range, 42.0-496,000 micrograms/l) was significantly higher (t = 2.63, 0.01 > p> 0.001) than in normal age-matched controls (mean, 55.6 micrograms/l; range, 10.0-348.0 micrograms/l). A negative correlation was found between the serum HAE activity and the HA concentration (r = -0.45, t = 5.92, p < 0.001). The possible reasons for the low serum HAE activity and the raised serum HA concentration in patients with disseminated neoplasm and the negative correlation between the results are discussed.
Phage display vectors for in vivo recombination of immunoglobulin heavy and light chain genes to make large combinatorial libraries.
New phage display vectors for in vivo recombination of immunoglobulin (Ig) heavy (VH) and light (VL) chain variable genes, to make single-chain Fv fragments (scFv), were constructed. The VH and VL genes of monoclonal antibody (mAb) EP-5C7, which binds to both human E- and P-selectin, were cloned into a pUC19-derived plasmid vector, pCW93, and a pACYC184-derived phagemid vector, pCW99, respectively. Upon induction of Cre recombinase (phage P1 recombinase), the VH and VL genes were efficiently recombined into the same plasmid via the two loxP sites (phage P1 recombination sites), one located downstream from a VH gene in pCW93 and another upstream from a VL gene in pCW99. In the resulting phagemid, the loxP sequence also encodes a polypeptide linker connecting the VH and VL domains to form a scFv of EP-5C7. Whether expressed on the phage surface or as a soluble form, the EP-5C7 scFv showed specific binding to human E- and P-selectin. This phagemid vector system provides a way to recombine VH and VL gene libraries efficiently in vivo to make extremely large Ig combinatorial libraries.
Measurement of hyaluronidase activity in normal human serum.
A detailed evaluation of the assay for serum hyaluronidase (HAE) activity originally developed by Bonner and Cantey [W.M. Bonner, Jr. and E.Y. Cantey, Clin. Chim. Acta, 13 (1966) 746-752] is described, together with studies of its precision. The method is based on the liberation of saccharides with N-acetylglucosamine (NAG) end-groups from hyaluronic acid. The NAG is quantitated by heating with alkaline tetraborate to form an intermediate which reacts with p-dimethylaminobenzaldehyde in acidic medium to form a coloured product. The optimised assay, which requires less that 50 microliters of serum, was used to study the HAE activity of 70 normal sera. The mean HAE activity was 17.1 mumol NAG min-1 l-1 (range 11.5-27.0 mumol NAG min-1 l-1); there was no significant difference with age (t = 1.65, 0.5 > P > 0.1) or sex (t = 0.33, P > 0.5).
Characterization of the major transcripts encoded by the regulatory MuDR transposable element of maize.
The MuDR element controls the transposition of the Mutator transposable element family in maize. Previous studies reported the presence of two major MuDR-homologous transcripts that correlate with Mutator activity. In this study, we describe the structure and processing of these two major transcripts. The transcripts are convergent, initiating from opposite ends of the element within the 220-bp terminal inverted repeats. The convergent transcripts do not overlap, and only 200 bp of internal MuDR sequences are not transcribed. Cloning and sequencing of multiple MuDR cDNAs revealed unusual intron/exon junctions, differential splicing, and multiple polyadenylation sites. RNase protection experiments indicated that some splicing failure occurs in young seedlings, and that a low level of antisense RNA exists for both transcripts. On a whole plant level, the presence of the major MuDR transcripts strictly correlates with Mutator activity in that no MuDR transcripts are observed in non-Mutator or inactive Mutator stocks. Examination of various tissues from active Mutator stocks indicates that the two transcripts are present in all organs and tissues tested, including those with no apparent transposition activity. This suggests that Mutator activity is not simply controlled by the level of the major MuDR transcripts.
We do need a new Midwives' Act!
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Results of excimer laser photorefractive keratectomy for the correction of myopia.
PURPOSE: This report summarizes the authors' 3-year experience with excimer laser photorefractive keratectomy on 240 eyes of 161 patients. METHODS: With constant laser emission parameters, nitrogen flow across the cornea was used on 79 eyes, whereas 161 eyes had no nitrogen flow. Of the 240 eyes, 74 were operated on without suction ring fixation. Postoperative pain management included patching and oral analgesics in 77 eyes and the use of topical diclofenac or ketorolac and a therapeutic soft contact lens in 163 eyes. Follow-up ranged from 1 month (206 eyes) to 36 months (10 eyes). RESULTS: At 3 months, 88% (144 eyes) had uncorrected visual acuity of 20/40 or better; 86% (151 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 10% (17 eyes) lost two or more lines of best-corrected visual acuity. At 12 months, 89% (122 eyes) achieved uncorrected visual acuity of 20/40 or better, 79% (115 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 4% (6 eyes) lost two or more lines of best-corrected visual acuity. At 24 months, 92% (44 of 48 eyes) had uncorrected visual acuity of 20/40 or better, 86% (44 of 51 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 5% (2 eyes) lost two or more lines of best-corrected visual acuity. At 36 months, 90% (9 eyes) achieved an uncorrected visual acuity of 20/40 or better, 90% (9 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and no eyes lost two or more lines of best-corrected visual acuity. CONCLUSIONS: The results obtained with one procedure are within accepted standards of accuracy for refractive surgery, and there is the potential for refinement of the final optical correction. Complication rates are low and are not vision threatening. They included increased intraocular pressure, epithelial "map dot" changes, and recurrent corneal erosion syndrome, "central islands," and others. Photorefractive keratectomy appears to be a safe procedure over the short and medium term.
Insurance--why single out the independent midwife?
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A two-year experience with excimer laser photorefractive keratectomy for myopia.
PURPOSE: This report summarizes the authors' 2-year experience with excimer laser photorefractive keratectomy (PRK) on 160 eyes of 128 patients. METHODS: All eyes were treated with an excimer laser: fluence, 160 mJ/cm2; frequency, 5 Hz; ablation zone diameter, 5.0 to 5.5 mm; and depth per pulse, 0.21 to 0.27 microns. A suction fixation ring was used in all eyes either with nitrogen flow (79 eyes) or without nitrogen flow (81 eyes) across the cornea. Follow-up ranged from 1 month (152 eyes) to 24 months (12 eyes). RESULTS: At 3 months, 82% (139) of eyes achieved an uncorrected visual acuity of 20/40 or better; 83% were corrected to within +/- 1 diopter (D) of intended correction and 30% lost one line of best-corrected visual acuity. At 6 months, 88% (124) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 15% lost one line of best-corrected visual acuity. At 12 months, 91% (71) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 17% lost one line of best-corrected visual acuity. At 24 months, 100% (12) of eyes achieved an uncorrected visual acuity of 20/40 or better; 91.6% were within +/- 1 D of intended correction and 0% lost one line of best-corrected visual acuity. CONCLUSIONS: In eyes with a follow-up of 6 to 24 months, 77% to 100% achieved an uncorrected visual acuity of 20/40 or better and 84% to 92% were corrected to within +/- 1 D of the intended correction. The authors conclude that excimer laser PRK appears to be a safe procedure capable of correcting the eyes of patients with low to moderate myopia with approximately the same degree of accuracy as radial keratotomy.