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Biomedical subjects

J Carroll

Publications and source records attributed to J Carroll.

At least 127 records · Page 7Linked to original sources

Personal problem-solving scoring of TAT responses: known-groups validation.

Two studies employed a known-groups validation strategy to evaluate a Thematic Apperception Test (TAT) scoring system purported to measure personal problem-solving skills, the Personal Problem-Solving System (PPSS). In Study 1 clinicians rated the records of 46 mental health outpatients for the presence of personal problem-solving skills deficits. Verbatim TAT transcripts from these patients were blindly scored using the PPSS. Participants predicted to demonstrate problem-solving deficits obtained lower PPSS scores. In Study 2 a psychiatric sample (n = 47) and a community-based comparison group (n = 47) completed a life history questionnaire, a checklist of problems currently experienced, a measure of psychiatric symptoms, and responded to 3 TAT cards. TAT responses were again blindly scored using the PPSS. In contrast to the comparison group, psychiatric patients checked a greater number of current problems, endorsed more psychiatric symptoms, and obtained lower scores on the PPSS. A discriminant function analysis using PPSS scores correctly classified 72% of these participants. PPSS scores predicted group membership even after controlling for differences in age, education, the number of problems experienced, and psychiatric symptoms. This combination of variables correctly classified 92% of the participants. Results of both studies are interpreted as supporting the discriminant validity of the PPSS.

Journal Article↗

Aldosterone-producing adenomas do not contain glucocorticoid-remediable aldosteronism chimeric gene duplications.

In glucocorticoid-remediable aldosteronism (GRA) a chimeric gene has been described with the activity of aldosterone synthase, but the promoter of 11 beta-hydroxylase leading to ectopic expression of aldosterone synthase activity in the zona fasciculata. Similar to GRA, in aldosterone-producing adenomas (APA), the primary regulation of aldosterone production is ACTH, and there is increased production of the 18-oxygenated cortisol compounds, 18-oxocortisol and 18-hydroxycortisol. Because of these hormonal similarities, we tested whether a chimeric GRA-like gene was present in APA from 11 patients. A GRA-like chimeric gene was not found in the DNA from these tumors and, therefore, is not the mechanism responsible for hyperaldosteronism in APA.

Adenoma↗

Ca2+ release and the development of Ca2+ release mechanisms during oocyte maturation: a prelude to fertilization.

Oogenesis involves the production of an oocyte that can undergo fertilization and support early development. The stimulus that initiates embryogenesis is an increase in the concentration of intracellular Ca2+ in the cytoplasm of the oocyte at the time of fertilization. The development of the ability of the oocyte to release Ca2+ in response to the fertilizing spermatozoon is an essential step in the process of oogenesis. Mammalian oocytes are particularly useful for studying the development of Ca2+ signalling systems, owing to the series of Ca2+ oscillations generated at fertilization, compared with the monotonic Ca2+ increase seen in nonmammalian species. Recent evidence has revealed that Ca2+ release mechanisms are modified during oogenesis. The maximal sensitivity of Ca2+ release is reached in the final stages of oocyte maturation, just before the optimal time for fertilization. In this review, we consider the mechanism underlying Ca2+ release in mammalian oocytes and discuss how the release mechanisms are modified during oocyte maturation. The tight co-ordination of the differentiation of the Ca2+ signalling system with the development of the oocyte provides a means of ensuring successful activation at the time of fertilization. Finally, we consider the consequences for embryo development in circumstances in which the co-ordination is lost.

Animals↗

Attitudes to drug users according to age of staff.

The attitudes of professionals working with intravenous drug users, and their perceptions of service delivery, are likely to be affected by age. Younger professionals tend to be more positive in their attitudes towards intravenous drug users. Older professionals tend to be less concerned about the risks from HIV infection than younger ones. More research is needed into the effects of age group on attitudes.

Adult↗

Attitudes to drug users according to staff grade.

The attitudes of professionals working with intravenous drug users are likely to be affected by clinical grade. Perceptions of service delivery to intravenous drug users are likely to be affected by status. Senior professionals tend to be more positive in their attitudes towards intravenous drug users. Attitudes and perceptions of service delivery are very important in determining the standard of care delivery.

Adult↗

How family influences practice of obstetrics. Do married women family physicians make different choices?

PURPOSE: To examine the influence of family, past and current, on married women family physicians' and to understand why and how some women continue to practise obstetrics. PARTICIPANTS: Purposive sample of nine married women family physicians who currently practise obstetrics. METHOD: Qualitative in-depth interviews. FINDINGS: Analysis identified four main influences of family on participants' practice of obstetrics: family of origin, transitions in the life cycle, children, and the marital relationship. CONCLUSIONS: These women described how they combined the roles of wife, mother, daughter, sister, and doctor. Family was a powerful influence throughout their practice lives. Finding a balance between the demands of practice, particularly obstetrics, and family relationships was an ongoing process. The process was also influenced by transitions in the life cycle.

Adaptation, Psychological↗

Felodipine in the treatment of severe refractory hypertension.

The efficacy of felodipine and tolerance of this drug was examined in 52 patients, 23 men and 29 women, 18-76 years of age, in whom it either replaced previous therapies of nifedipine and other vasodilators, or was added to a constant dose of beta blockers and diuretics or another previous therapy, which was unchanged. Felodipine significantly reduced blood pressure (BP), from 192.3 +/- 31.9/114.3 +/- 18.0 to 155.7 +/- 19.5/93.8 +/- 11.5 mm Hg, with no change in pulse rate. There were no significant biochemical changes, renal deterioration or blood sugar disequilibrium. Adverse reactions including flushes and leg edema could be tolerated by most of the patients, however six patients dropped out. Orthostasis dictated a decrease in felodipine dosage. Felodipine appears to be a highly potent, well tolerated drug and offers a substitute treatment for severe hypertensives refractory to other vasodilators.

Adolescent↗

High-speed rotational atherectomy for chronic total coronary occlusions.

Treatment of chronic total occlusions remains a limitation of percutaneous revascularization and is associated with lower immediates success and higher long-term restenosis rates compared to less severe stenoses. While part of the problem in dealing with total occlusions relates to successfully passing a wire across the occluded segment, most chronic occlusions contain large plaque burdens. Balloon dilatation sometimes falls to restore antegrade flow and often yields suboptimal angiographic results in these situations. Rotational atherectomy has proven useful in treating calcified and diffusely-diseased vessels and appears attractive for debulking lesions with large atheromatous plaques. We report our experience using rotational atherectomy in treating chronic total occlusions.

Aged↗

Ionomycin, thapsigargin, ryanodine, and sperm induced Ca2+ release increase during meiotic maturation of mouse oocytes.

Fertilization of mature mouse oocytes triggered highly repetitive Ca2+ oscillations lasting 2-3 h. However, immature oocytes generated only two or three oscillations, which ceased within 1 h. Development of repetitive Ca2+ transients to sperm occurred late in oocyte maturation and was dependent on cytoplasmic modifications that were independent of cell cycle progression from metaphase I to metaphase II. Immature oocytes released significantly less Ca2+ from stores than mature oocytes in response to ionomycin and thapsigargin. Ryanodine had no effect on intracellular Ca2+ in maturing oocytes but stimulated an increase in Ca2+ in mature oocytes. The ability of ryanodine to increase Ca2+ levels was, however, strain-dependent. Preincubation of oocytes with thapsigargin or ryanodine significantly attenuated the normal fertilization Ca2+ response, causing a decrease in the number and the rate of rise of the transients. The inhibition of sperm-induced Ca2+ transients by ryanodine was independent of its ability to cause an immediate Ca2+ increase. Low concentrations of ryanodine had no effect on resting Ca2+ levels but inhibited Ca2+ oscillations at fertilization. Similarly Ca2+ oscillations were blocked in oocytes from a strain of mouse that showed no immediate Ca2+ increase with ryanodine. These results suggest that modifications in Ca2+ stores and ryanodine-sensitive Ca2+ release mechanisms during oocyte maturation play an important role in Ca2+ oscillations at fertilization.

Animals↗

Experimental autoimmune encephalomyelitis-resistant mice have highly encephalitogenic myelin basic protein (MBP)-specific T cell clones that recognize a MBP peptide with high affinity for MHC class II.

BALB/c mice are resistant to disease induction when experimental protocols that induce experimental autoimmune encephalomyelitis (EAE) in susceptible strains of animals are used. We have previously described a panel of myelin basic protein (MBP)-specific CD4+ T cell clones from BALB/c mice, two of which induce moderate EAE when transferred to syngeneic recipients. These clones are I-E(d) restricted and recognize residues 151-160 of mouse MBP. Here, we describe a series of 17 MBP-reactive T cell clones, which were derived from two BALB/c mice. All are I-A(d) restricted and recognize nested epitopes in peptide 59-76 of mouse MBP. Four different TCR V beta chains are used by this panel of clones; these include V beta 8.2 (10/17), V beta 8.1 (2/17), V beta 7 (3/17), and V beta 14 (2/17). Twelve of fourteen clones tested adoptively transferred severe demyelinating EAE to syngeneic recipients. Studies of relative binding affinities of MBP peptides to class II molecules I-A(d) and I-E(d) show that peptide 59-76 binds with extremely high affinity to I-A(d), whereas three peptides that contains residues 151-160 bind poorly to I-E(d). These results are consistent with a growing number of reports that show that high affinity binding to class II is required for autoantigenic stimulation. Despite encephalitogenicity of 59-76-reactive T cells, active immunization of BALB/c mice with peptide 59-76 in adjuvant failed to induce either clinical or histologic signs of EAE. The implications of these findings for mechanisms of genetically determined EAE resistance are discussed.

Amino Acid Sequence↗

The effect of enalapril with and without hydrochlorothiazide on insulin sensitivity and other metabolic abnormalities of hypertensive patients with NIDDM.

The effect of 20 mg of enalapril with and without 12.5 mg of hydrochlorothiazide on glucose metabolism insulin sensitivity and lipids was evaluated in hypertensive non-insulin-dependent diabetes. Ten mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus were treated for 8 weeks with 20 mg enalapril once a day, and then divided into two groups of 5 patients each for a second 8 weeks of treatment with enalapril alone or in combination with hydrochlorothiazide, 12.5 mg once a day. Blood pressure, fasting plasma glucose, lipids and insulin, glycosylated hemoglobin, and insulin sensitivity were measured at baseline and after 8 and 16 weeks. Results were analyzed by the ANOVA test for repeated measures and all values are given as mean +/- SD. Diastolic blood pressure decreased significantly after the first and second period of enalapril and after the combination of enalapril and hydrochlorothiazide. Glycosylated hemoglobin dropped significantly after the first and second period of enalapril monotherapy. Plasma triglycerides and fasting plasma insulin decreased significantly after the 16 weeks of enalapril. Insulin-mediated glucose uptake increased significantly after 8 and 16 weeks of monotherapy with enalapril. No significant difference was observed in any of the metabolic characteristics, including insulin sensitivity, between the values after 8 weeks of enalapril alone and the final values of the enalapril-treated and the enalapril/hydrochlorothiazide-treated groups. It is concluded that enalapril improves some of the metabolic parameters, including insulin sensitivity, of hypertensive diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial.

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.

Analysis of Variance↗

The value of plasma calibrants in correcting coagulometer effects on international normalized ratios. An international multicenter study.

A study of lyophilized plasma calibrants in correcting for coagulometer effects on International Normalized Ratios (INR) has been conducted in an international survey. Prothrombin times were performed with the calibrants on 2 "common" thromboplastins and in-house thromboplastins in 3 brands of coagulometer at 37 centers. The International Sensitivity Indices (ISI) of 95 local systems with the calibrants were derived. The "true" INR of 10 test plasmas from warfarin-treated patients were established centrally using thromboplastin International Reference Preparations (IRP). International Normalized Ratios of these plasmas for each center were calculated using both the manufacturers' stated and the local ISI. The mean deviation of the 95 systems from the "true" INR of the warfarin plasmas was +14.4% with the manufacturers' ISI, but reduced to +1.04% with the local ISI. Local ISI determination with the calibrants avoids many of the difficulties of conventional thromboplastin calibrations. Plasmas from patients on warfarin and parallel manual PT with thromboplastin IRP are not required.

Blood Coagulation Tests↗

A comparison of lyophilized artificially depleted plasmas and lyophilized plasmas from patients receiving warfarin in correcting for coagulometer effects on international normalized ratios.

The comparative value of lyophilized artificially depleted plasmas and plasmas from warfarin-treated patients in local (thromboplastin/coagulometer) system International Sensitivity Indices (ISI) determination has been studied at 39 centers in an international collaborative study. At each center, both types of plasmas were tested with two common thromboplastins (low ISI RecombiPlasTin and high ISI OBT), and in-house reagents using three brands of coagulometers. In 95 local systems, they was agreement. With both thromboplastins, coagulometers lowered the ISI from the manual or stated ISI with all systems. Differences between the two types of lyophilized plasmas with the two common thromboplastins were not of clinical importance. Artificially depleted plasmas are easier to obtain in sufficient volumes than plasma from warfarin-treated patients, and more easily provide the wide range of INR values required for reliable local ISI calibration. The agreement between the two types of lyophilized calibrant is reassuring.

Blood Coagulation Tests↗

Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine: cross-over study.

The lack of comparative studies of nifedipine and felodipine using 24-h blood pressure (BP) monitoring in the same patients led to the present study evaluating the antihypertensive efficacy and side effects of treatment with slow-release (SR) nifedipine (20 mg twice daily) and extended-release (ER) felodipine (10 mg once daily). In the double-blind study, subjects were randomly assigned to one of two treatment groups: 6 weeks of nifedipine SR (20 mg twice daily) followed by 6 weeks of felodipine (ER) (10 mg once daily with evening matched placebo), or vice versa. Twenty-four-hour ambulatory BP monitoring showed no significant differences in systolic BP (SBP) during the day. There were no significant differences in diastolic BP (DBP) throughout the 24 h, although the frequency of DBP recordings > 90 mm Hg was greater during nifedipine (33.1%) than felodipine (27.75%) treatment. The most common side effects were flushing, palpitations, headaches, and ankle edema; there were no adverse effect on lipid profile or glucose level.

Adolescent↗

Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei.

We studied 19 symptomatic female carriers of the Duchenne muscular dystrophy (DMD) gene. Most of these dystrophinopathy patients had had an erroneous or ambiguous diagnosis prior to dystrophin immunofluorescence testing. We assessed clinical severity by a standardized protocol, measured X-chromosome inactivation patterns in blood and muscle DNA, and quantitated the dystrophin protein content of muscle. We found that patients could be separated into two groups: those showing equal numbers of normal and mutant dystrophin genes in peripheral blood DNA ("random" X-inactivation), and those showing preferential use of the mutant dystrophin gene ("skewed" X-inactivation). In the random X-inactivation carriers, the clinical phenotype ranged from asymptomatic to mild disability, the dystrophin content of muscle was > 60% of normal, and there were only minor histopathologic changes. In the skewed X-inactivation patients, clinical manifestations ranged from mild to severe, but the patients with mild disease were young (5 to 10 years old). The low levels of dystrophin (< 30% on average) and the severe symptoms of the older patients suggested a poor prognosis for those with skewed X-inactivation, and they all showed morphologic changes of dystrophy. The random inactivation patients showed evidence of biochemical "normalization," with higher dystrophin content in muscle than predicted by the number of normal dystrophin genes. Seventy-nine percent of skewed X-inactivation patients (11/14) showed genetic "normalization," with proportionally more dystrophin-positive nuclei in muscle than in blood. In 65% of the skewed X-inactivation patients, dystrophin was not produced by dystrophin-positive nuclei; an average of 20% of myofiber nuclei were genetically dystrophin-positive but did not produce stable dystrophin. Biochemical normalization seems to be the main mechanism for rescue of fibers from dystrophin deficiency in the random X-inactivation patients. In the skewed X-inactivation patients, genetic normalization is active, but production failure of dystrophin by dystrophin-normal nuclei may counteract any effect of biochemical normalization. In the skewed X-inactivation patients, the remodeling of the muscle through cycles of degeneration and regeneration led to threefold increase in the number of dystrophin-competent nuclei in muscle myofibers (3.3 +/- 4.6), while dystrophin content was on the average 1.5-fold less then expected (-1.54 +/- 3.38). Our results permit more accurate prognistic assessment of isolated female dystrophinopathy patients and provide important data with which to estimate the potential effect of gene delivery (gene therapy) in DMD.

Adult↗

Repetitive sperm-induced Ca2+ transients in mouse oocytes are cell cycle dependent.

Mature mouse oocytes are arrested at metaphase of the second meiotic division. Completion of meiosis and a block to polyspermy is caused by a series of repetitive Ca2+ transients triggered by the sperm at fertilization. These Ca2+ transients have been widely reported to last for a number of hours but when, or why, they cease is not known. Here we show that Ca2+ transients cease during entry into interphase, at the time when pronuclei are forming. In fertilized oocytes arrested at metaphase using colcemid, Ca2+ transients continued for as long as measurements were made, up to 18 hours after fertilization. Therefore sperm is able to induce Ca2+ transients during metaphase but not during interphase. In addition metaphase II oocytes, but not pronuclear stage 1-cell embryos showed highly repetitive Ca2+ oscillations in response to microinjection of inositol trisphosphate. This was explored further by treating in vitro maturing oocytes at metaphase I for 4-5 hours with cycloheximide, which induced nuclear progression to interphase (nucleus formation) and subsequent re-entry to metaphase (nuclear envelope breakdown). Fertilization of cycloheximide-treated oocytes revealed that continuous Ca2+ oscillations in response to sperm were observed after nuclear envelope breakdown but not during interphase. However interphase oocytes were able to generate Ca2+ transients in response to thimerosal. This data suggests that the ability of the sperm to trigger repetitive Ca2+ transients in oocytes is modulated in a cell cycle-dependent manner.

Animals↗

Nuclei from fertilized mouse embryos have calcium-releasing activity.

During mammalian fertilization, the sperm triggers a series of intracellular Ca2+ oscillations which initiate oocyte activation and the formation of pronuclei. Oocyte activation can be induced artificially by a variety of chemical and physical stimuli which elevate intracellular calcium. We show that the transfer of nuclei from 1- and 2-cell-stage fertilized mouse embryos to unfertilized oocytes stimulates the completion of meiosis and the formation of pronuclei. Nuclei from embryos that had developed to the 4-cell stage did not stimulate meiotic resumption. The ability to cause oocyte activation was specific to nuclei transferred from fertilized embryos as nuclei from parthenogenetic embryos or cytoplasts from fertilized or parthenogenetic embryos did not induce activation. Nucleus-induced oocyte activation was associated with the generation of intracellular Ca2+ transients, which were seen after nuclear envelope breakdown of the transferred nuclei. Treatment of the oocyte with the intracellular Ca2+ chelator, BAPTA, prior to nuclear transfer inhibited intracellular Ca2+ transients and oocyte activation. The specific Ca(2+)-releasing activity of the nucleus was not caused by sperm-induced protein synthesis since similar activity was present in nuclei originating from embryos exposed to cycloheximide throughout fertilization. The specific ability of nuclei from fertilized embryos to stimulate Ca2+ transients and oocyte activation was also found in nuclei from embryos parthenogenetically activated by the injection of a partially purified cytosolic sperm factor. The results suggest that the fertilizing sperm introduces Ca(2+)-releasing activity which becomes associated with the nucleus of early mammalian embryos.

Animals↗