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Biomedical subjects

C Taylor

Publications and source records attributed to C Taylor.

At least 271 records · Page 15Linked to original sources

Stress and cancer surveys: attitudes of participants in a case-control study.

STUDY OBJECTIVE: The aim was to ascertain whether personal interviews carried out for cancer case-control studies cause stress to participants. DESIGN: Retrospective postal questionnaires were sent to women at least three months after interview for a case-control study of the aetiology of cervical cancer. The questionnaire covered attitudes to taking part in the study, stress engendered by participation, whether any particular questions were distressing, factors relevant to the decision to participate, and the role of their doctor with respect to participation. SETTING: South East and South West Thames health regions, United Kingdom. PATIENTS: Patients were women aged 20-45 years at diagnosis with invasive cervical cancer, and population based controls. MEASUREMENTS AND MAIN RESULTS: The response rate was 90%. Nearly all respondents were glad they had participated, while only 2/226 regretted taking part. Half the respondents (115/226) perceived some actual benefit from taking part. The interview carried out in the case-control study was both long and detailed and included topics such as numbers of sexual partners and history of sexually transmitted diseases. As expected, the questions causing most concern to interviewees were those on number of sexual partners, but only 13% of participants were bothered by these questions and only 4% felt inclined to terminate the interview early. CONCLUSIONS: The lack of evidence of stress caused by this potentially difficult interview suggests that, in the hands of experienced interviewers, stress is unlikely to be caused by participation. Many participants felt that they had benefited from taking part. Doctors and ethics committees should find these results reassuring.

Adult↗

Follicular dynamics and temporal relationships among body temperature, oestrus, the surge of luteinizing hormone and ovulation in Holstein heifers treated with norgestomet.

The effects of chronic treatment with norgestomet on follicular dynamics, corpus luteum growth and function as well as the temporal relationships among body temperature, oestrous behaviour, the luteinizing hormone (LH) surge and ovulation following implant removal were studied in 16 Holstein heifers. Oestrous cycles of the heifers were initially synchronized using 2 injections of prostaglandin F-2 alpha (PGF-2 alpha) 12 days apart. The heifers were then implanted with a norgestomet ear implant for 9 days, beginning either at the middle of the synchronized cycle (dioestrus) or at the end of the synchronized cycle (pro-oestrus). Follicular dynamics, corpus luteum growth and regression, and plasma progesterone were not affected by norgestomet treatment at dioestrus. The dominant follicle present at the time of norgestomet implantation in the pro-oestrus group was maintained during the 9-day implant period of 6 of 8 heifers and ovulated after implant removal. Time from implant removal to onset of standing oestrus and time to LH peak following implant removal were highly correlated with the time of ovulation (r = 0.92 and 0.96, respectively). Onset of standing oestrus and the LH peak and the onset of standing oestrus and peak vaginal and rectal temperatures were also highly correlated (r = 0.96, 0.82 and 0.81, respectively). It is concluded that any decrease in pregnancy rates following treatment with norgestomet is not due to asynchrony among oestrus, the LH surge and ovulation.

Animals↗

Follicular dynamics and corpus luteum growth and function in pregnant versus nonpregnant cows.

The effects of pregnancy on follicular dynamics and corpus luteum growth and function are somewhat contentious. In an effort to learn more about the effects of pregnancy, the reproductive tracts of 16 bred dairy cows were monitored using an ultrasound device with a rectal probe through the first 60 d of pregnancy or upon a return to estrus. Additionally, blood samples were collected for progesterone determination. Eleven of 16 cows were diagnosed pregnant by 25 d postbreeding. There were two embryonic mortalities between 28 and 32 d. A two-wave pattern of follicular growth and atresia, each wave resulting in a large dominant follicle, was seen in both pregnant and nonpregnant cows during the first 24 d postbreeding. Pregnant cows had more follicles than nonpregnant cows; however, there was no difference in the size of the largest follicle. A wave-like pattern of growth of large follicles continued throughout the study period in pregnant cows. Progesterone profiles, corpus luteum growth rate, and maximum size of the corpus luteum were similar in both pregnant and nonpregnant cows. It is concluded that growth of dominant follicles and of the corpus luteum is unaffected during the first 60 d of pregnancy.

Animals↗

The genomic organization of the CD28 gene. Implications for the regulation of CD28 mRNA expression and heterogeneity.

CD28 is a 90-kDa homodimeric glycoprotein present on the surface of a large subset of T cells that appears to play an important role in the modulation of T cell activation. Although a number of physiologic effects associated with CD28 stimulation have been defined, relatively less is known about the structure and expression of the CD28 gene itself. We now show that CD28 is expressed in both Th cells and plasma cells as a series of four distinct CD28 mRNA species: 1.3-, 1.5-, 3.5-, and 3.7-kb transcripts. The steady state expression of all four transcripts in CD28+ T cells was stimulated by PMA, suggesting that they might share a common phorbol-sensitive promoter. Consistent with this hypothesis, CD28 was found to be encoded by a single copy gene organized into four exons, each exon defining a functional domain of the predicted protein. All CD28 transcripts appear to initiate within a 61-bp palindrome. Generation of the four CD28 mRNA species from the CD28 gene involves two distinct posttranscriptional events. The longer pair of transcripts (3.5/3.7 kb) is generated by the use of an alternate nonconsensus polyadenylation signal. This results in the addition of 2167 bp beyond the first polyadenylation site utilized by the shorter (1.3/1.5 kb) pair of transcripts. The size difference between the 3.7- and 3.5-kb messages and between the 1.5- and 1.3-kb messages is generated by an internal splicing event that deletes 252 bp within exon 2, which encodes the extracellular domain. This deletion would result in the loss of 84 amino acids, including 4 of 5 extracellular cysteine residues. Although this deletion would result in significant disruption of CD28 secondary structure, it would not be expected to interfere with the ability of the resultant protein to be expressed on the cell surface. These findings suggest that variant isotypes of CD28 may be expressed on the cell surface with potentially different physiologic roles.

Amino Acid Sequence↗

Ethics in health care and medical technologies.

In this paper a case is used to demonstrate how ethical analysis enables health care professionals, patients and family members to make treatment decisions which ensure that medical technologies are used in the overall best interests of the patient. The claim is made and defended that ethical analysis can secure four beneficial outcomes when medical technologies are employed: (1) not allowing any medical technologies to be employed until the appropriate decision makers are identified and consulted; (2) insisting that medical technologies be employed not merely to promote the medical interests of the patient but rather on the basis of their ability to contribute to the overall well-being of the patient; (3) challenging caregivers to reflect on the dynamic interplay between their conscious and unconscious values and consequent determinations of what is in the patient's best interests; and (4) providing a justification for selected interventions which makes possible rational dialogue between caregivers espousing different viewpoints about treatment options.

Beneficence↗

What happens to drug misusers? A medium-term follow-up of subjects new to treatment.

In a 2.5-5 year follow-up study of 150 drug misusers who were new to treatment at three London Drug Treatment agencies, a 77% follow-up rate was obtained. High rates of self-reported abstinence from opiates and other drugs were found. Some 37% of those followed-up were totally drug free at follow-up. Seventy-one per cent were living in the community and of those 73% were opiate free and 35% were totally drug free. Only 18% had injected in the 4 weeks prior to follow-up. Thirteen per cent were in prison and 12% were resident in a therapeutic community. Being told about the dangers of HIV had persuaded some people to give up using drugs.

Adult↗

Multiple-dose pharmacokinetics of oral zidovudine in hemophilia patients with human immunodeficiency virus infection.

The disposition of zidovudine (ZDV) was examined during chronic oral dosing (300 mg every 4 h while awake) for 12 weeks in eight asymptomatic patients with hemophilia who were infected with the human immunodeficiency virus. Pharmacokinetic studies were conducted at the initiation of drug administration and after 6 and 12 weeks. Baseline liver function tests indicated normal values for bilirubin, albumin, and prothrombin time, while hepatic enzyme levels ranged from one to three times the normal levels. Initially, the mean peak ZDV concentration in plasma was 2,052 ng/ml with a range of 1,033 to 3,907 ng/ml, while during chronic dosing the peaks were 1,619 +/- 1,062 ng/ml and 1,711 +/- 786 ng/ml at weeks 6 and 12, respectively. ZDV concentrations at 4 h declined to 77 +/- 53 ng/ml, 110 +/- 43 ng/ml, and 101 +/- 49 ng/ml at weeks 1, 6, and 12, respectively. Initially, the plasma concentration-versus-time decay in three patients was linear, with a mean half-life (t1/2) of 1.3 +/- 0.5 h, while five patients had detectable concentrations in plasma after 4 h with an apparent delayed terminal-phase t1/2 of 4.8 +/- 2.8 h. At week 6 the prolonged elimination pattern was noted in all patients (terminal t1/2 = 4.1 +/- 2.0 h). No correlation between hepatic enzyme levels and t1/2 was noted. These findings suggest that ZDV may display a prolonged elimination phase during multiple dosing. Further studies utilizing a more sensitive assay may help to further define this later phase of ZDV elimination.

Administration, Oral↗

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass.

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.

Arteries↗

Reversal of progressive nyctalopia in a patient with Crohn's disease.

A 51-year-old man who had undergone several partial bowel resections for Crohn's disease presented with progressively decreased night vision. Electroretinography showed a flat scotopic response and a diminished, delayed photopic response. Measurement of stool fat showed marked fat malabsorption. Treatment with parenteral nutrition, including administration of vitamin A, resulted in marked improvement in the scotopic and photopic response and subjective improvement in his night vision. Patients with malabsorption states should be followed to avoid irreversible visual loss.

Color Perception↗

The use of do-not-hospitalize orders by family physicians in Ohio.

A sample of Ohio family physicians was surveyed by mail questionnaire regarding physician attitudes and practices concerning do-not-hospitalize (DNH) orders. One hundred seventy-three of the 210 physicians who completed the survey provided care for patients in nursing homes. Fifty-eight percent of physicians caring for nursing home patients were familiar with the concept of do not hospitalize, and 42% had utilized a DNH order. The most commonly named reasons for using a DNH order were patient's terminal condition and patient's request. The most common reasons physicians did not use a DNH order were because of family objections and the inability of nursing homes to deliver intravenous antibiotics and fluids. Almost all physicians had encountered a clinical situation where a DNH order might be appropriate, and 73% of physicians familiar with the DNH concept had utilized the order. Familiarizing more physicians with the concept of DNH orders may have great potential for reducing health care costs and preserving patient autonomy. Future studies are needed to validate the concept of do not hospitalize.

Adult↗

Pharmacokinetics of orally administered zidovudine among patients with hemophilia and asymptomatic human immunodeficiency virus (HIV) infection.

Zidovudine (formerly azidothymidine, AZT) is used to treat certain patients infected with the human immunodeficiency virus (HIV). However, the clinical use of zidovudine (ZDV) in hemophilia patients may be complicated by the high incidence of chronic hepatitis in this patient population. To examine the pharmacokinetics of ZDV eight asymptomatic HIV-infected hemophilia patients received a single oral dose (300 mg). ZDV and its glucuronide metabolite (GZDV) were measured in serum by HPLC. ZDV was rapidly absorbed with a wide range of peak serum concentrations (2052 +/- 970 ng/ml) at 0.5 h. Peak GZDV serum concentrations were 4751 +/- 2269 ng/ml at 1 h. Both ZDV and GZDV declined in a biexponential manner over 4 h. After 4 h, the ZDV serum concentration decay in three patients continued a log-linear decline, while five patients demonstrated a tri-exponential curve which had a mean terminal elimination half-life of 4.8 +/- 2.8 h. No relationship between ZDV or GZDV kinetics and the degree of hepatic enzyme elevation was observed. Although a therapeutic window for ZDV has yet to be described, the wide range of serum concentrations that result from a standard dose suggests that clinical monitoring of ZDV levels may be of value in certain patients. In addition, the prolonged elimination half-life of ZDV in the present study may provide a rationale for less frequent dosing in certain patients.

Administration, Oral↗

Individual variability of amiodarone distribution in plasma and erythrocytes: implications for therapeutic monitoring.

The complexity of amiodarone disposition in blood and tissues gives rise to difficulty in determination of optimal therapeutic monitoring strategies. We have defined the within-patient variability of plasma and erythrocyte amiodarone and desethylamiodarone concentrations and electrocardiogram intervals [PR and corrected QT (QTc)] in 27 patients each sampled on three to four occasions during long-term stable amiodarone therapy. All individual repeated measurements were included in the concentration-effect analysis. The mean within-patient coefficients of variation for amiodarone and desethylamiodarone were significantly greater in erythrocytes, 46.0 and 24.5%, respectively, compared with plasma, 12.7 and 12.3%. Amiodarone and desethylamiodarone were significantly greater in erythrocytes, 46.0 and 24.5%, respectively, compared with plasma, 12.7 and 12.3%. Amiodarone and desethylamiodarone were strongly correlated (r = 0.29 p less than 0.004). There was a 10-fold variability in erythrocyte amiodarone for a given plasma level. These data emphasize the highly variable cellular distribution of amiodarone and desethylamiodarone in the same patient on stable dosage over time. Plasma amiodarone was significantly correlated with dosage (r = 0.98), and percent change in QTc, (r = 0.56, p less than 0.0001), but there was a fourfold variation in plasma amiodarone for a given QTc. Side-effect frequency was not related to plasma or erythrocyte amiodarone or desethylamiodarone concentrations. A clinically useful relationship between plasma concentration and effect could not be consistently demonstrated for amiodarone in the same individual during stable dosage.

Adult↗

Skin test studies on close contacts of leprosy patients in India.

Skin-test studies with a series of tuberculins have been carried out in close contacts of multibacillary (MB) leprosy patients around three leprosy centers in India, and casual contacts of the disease around two centers. The results show that the rate of acquisition of leprosin A positivity is associated with age and the closeness of contact with MB leprosy. At the age of 15 years, the differences between the two types of contact were highly significant (p less than 0.00001). Many responses to leprosin A are directed toward the group iv species-specific, antigens of the leprosy bacillus, and the significance of positivity is discussed in relation to protective immunity from leprosy. The differences from Iran show that positivity to leprosin A is not solely the effect of the degree of contact with the disease, but must also have a genetic or environmental element, the latter being favored. The results from Miraj show that the high levels of tuberculin, scrofulin, and vaccin positivity seen in Fathimanagar, and to a lesser extent in Karigiri, are not a consequence of contact with leprosy. BCG vaccination made little difference to the leprosin A positivity of close contacts of leprosy patients, although it significantly enhanced positivity among casual contacts around Miraj (p less than 0.002). BCG vaccination significantly increased tuberculin positivity in Miraj and Karigri, and in those under 11 years of age in Fathimanagar. It made no difference to the already high level of positivity found in older persons around Fathimanagar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗