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Biomedical subjects

D Shaw

Publications and source records attributed to D Shaw.

At least 73 records · Page 4Linked to original sources

Comparison of the vasoconstrictor effects of rizatriptan and sumatriptan in human isolated cranial arteries: immunohistological demonstration of the involvement of 5-HT1B-receptors.

AIMS: We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT1B/1D-receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT1B- or 5-HT1D-receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. METHODS: Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT1B- or 5-HT1D-receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (ANOVA) and nonlinear regression analysis. RESULTS: 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC50 values=32, 90 and 71 nM, respectively). A significantly higher level of 5-HT1B-receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (ANOVA, F=7.95, DF=1,4, P<0.05). CONCLUSIONS: Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT1B-receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.

Adult↗

Perfectionism, the imposter phenomenon and psychological adjustment in medical, dental, nursing and pharmacy students.

Extensive attention has been paid over the past three decades to the stressors involved in training in the health professions. Although empirical studies have identified demographic subgroups of students most likely to become distressed during training, less research has been carried out to evaluate the impact of students' personality characteristics on their adjustment. Severe perfectionism is one such personality trait that has been shown to increase the risk for anxiety and depressive disorders in other populations. Another set of personality traits linked to increased psychological problems has been labelled the 'impostor phenomenon', which occurs when high achieving individuals chronically question their abilities and fear that others will discover them to be intellectual frauds. Both perfectionism and the impostor phenomenon would seem to be pertinent factors in the adjustment of health professional students; however, these character traits have not been empirically examined in this population. In the present study psychological distress, perfectionism and impostor feelings were assessed in 477 medical, dental, nursing and pharmacy students. Consistent with previous reports, the results showed that a higher than expected percentage of students (27.5%) were currently experiencing psychiatric levels of distress. Strong associations were found between current psychological distress, perfectionism and impostor feelings within each programme and these character traits were stronger predictors of psychological adjustment than most of the demographic variables associated previously with distress in health professional students. Implications for future research, limitations of this study and clinical recommendations are discussed.

Adaptation, Psychological↗

Family systems therapy after Operation Desert Storm with European-theater veterans.

We describe a quasi-experimental trial of time-limited family therapy with veterans and families of veterans who served in Europe, outside the war zone, during Operation Desert Storm (ODS). Family systems therapy was provided both to individuals and conjointly to couples or families during the acute postwar readjustment period. The intervention adapted strategies from structural, strategic, intergenerational, and behavioral family therapies in a brief-treatment protocol for systemic stressor resolution. Veterans given family system therapy were able to resume functional levels of psychosocial adjustment and reduce the risk of long-term (chronic or delayed) psychosocial impairment. Based on these preliminary findings, controlled evaluation of family systems therapy appears warranted for individuals and families exposed to subtraumatic stressors such as wartime non-war-zone military deployment.

Adult↗

Molecular characterisation and hormone-dependent expression of the porcine whey acidic protein gene.

A 17.5 kDa protein was isolated from porcine whey by reverse phase HPLC and identified as a putative whey acidic protein (WAP) homologue by sequencing 35 and 40 amino acid residues of the amino- and carboxy-terminus respectively. Degenerate oligonucleotides to both of these amino acid sequences were designed and used in reverse transcriptase PCR with RNA from lactating porcine mammary gland as a template. A 162 bp PCR fragment was detected and sequenced. Compilation of the deduced and determined amino acid sequence revealed a protein of 111 amino acids, which had approximately 75, 50, 40 and 35% similarity at amino acid level to camel, rabbit, rat and mouse WAP respectively. It also included the four-disulphide core characteristic of all WAP proteins and most Kunitz-type protease inhibitors. This provides the first unequivocal evidence for WAP secretion in the pig. SDS PAGE analysis of the whey fraction showed that WAP is secreted as a major protein in sow's milk from farrowing to weaning. The molecular mass of WAP in SDS PAGE was significantly greater than the 11.7 kDa determined from amino acid sequence, indicating that porcine WAP is possibly glycosylated. Northern analysis detected a single mRNA transcript of approximately 600 bp in porcine RNA from the mammary gland of lactating sows. To examine the hormone-regulated expression of the WAP gene the mammary glands of sows at day 90 of pregnancy were biopsied and explants cultured for 3 days in the presence of various combinations of porcine insulin (I), cortisol (F) and porcine prolactin (P). Northern analysis of RNA extracted from the tissue indicated that WAP gene expression was barely detectable in the mammary gland prior to culture and there was no increment in explants cultured in the presence of I and F. However, a significant increase in the accumulation of WAP mRNA was observed in explants cultured in I, F and P. A similar result was observed for beta-casein and alpha-lactalbumin gene expression.

Amino Acid Sequence↗

Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.

Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Animals↗

Renal artery stent placement: utility in lesions difficult to treat with balloon angioplasty.

OBJECTIVES: We assessed the safety and efficacy of stent placement in patients with poorly controlled hypertension and renal artery stenoses, which are difficult to treat with balloon angioplasty alone. BACKGROUND: Preliminary experience with stent placement suggests improved results over balloon angioplasty alone in patients with atherosclerotic renal artery stenosis. METHODS: Balloon-expandable stents were placed in 100 consecutive patients (133 renal arteries) with hypertension and renal artery stenosis. Sixty-seven of the patients had unilateral renal artery stenosis treated and 33 had bilateral renal artery stenoses treated with stents placed in both renal arteries. RESULTS: Angiographic success, as determined by quantitative angiography, was obtained in 132 (99%) of 133 lesions. Early clinical success was achieved in 76% of the patients. Six months after stent placement, the systolic blood pressure was reduced from 173 +/- 25 to 147 +/- 23 mm Hg (p < 0.001); the diastolic pressure from 88 +/- 17 to 76 +/- 12 mm Hg (p < 0.001); and the mean number of antihypertensive medications per patient from 2.6 +/- 1 to 2.0 +/- 0.9 (p < 0.001). Angiographic follow-up at a mean of 8.7 +/- 5.0 months in 67 patients revealed restenosis (>50% diameter narrowing) in 15 (19%) of 80 stented vessels. CONCLUSIONS: Renal artery stenting is an effective treatment for renovascular hypertension, with a low angiographic restenosis rate. Stent placement appears to be a very attractive therapy in patients with lesions difficult to treat with balloon angioplasty such as renal aorto-ostial lesions and restenotic lesions, as well as after a suboptimal balloon angioplasty result.

Aged↗

Effects of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina or congestive heart failure.

This study evaluates the effect of renal artery stent implantation in patients with renovascular hypertension presenting with unstable angina (n = 20) or congestive heart failure (n = 28). There was a significant improvement in the Canadian Cardiovascular Society angina class and the New York Heart Association functional class, and at 8.4 +/- 6.4 month follow-up.

Aged↗

Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in vivo studies.

Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) that contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.

Animals↗

Effect of gender on outcomes following renal artery stent placement for renovascular hypertension.

To study the effect of gender on outcome following renal artery stent placement for renovascular hypertension, we prospectIvely followed 66 patients (30 males, 36 females) who underwent Palmaz stent placement in 89 renal arteries. There was no difference in the incidence of procedure-related complications between males and females. At 6-mo follow-up, the decrease in systolic (35 +/- 30 mm Hg and 27 +/- 25 mm Hg) and diastolic (15 +/- 23 mm Hg and 14 +/- 14 mm Hg) blood pressures was similar in female and male patients, respectIvely. Late follow-up at 19 +/- 11 mo also showed no difference in blood pressure response. In 44 patients who underwent repeat angiography at a mean duration of 9.1 +/- 5.6 mo after stent deployment, the incidence of restenosis was 26% in females and 24% in males (P = 0.85). We conclude that gender has no effect on the incidence of complications, blood pressure response, or angiographic restenosis in patients undergoing renal artery stent placement.

Aged↗

Amino acid sequence of bovine gamma E (IVa) lens crystallin.

When electrospray ionization mass spectrometry (ESMS) was used to analyze purified bovine gamma E (gamma IVa)-crystallin, it yielded a relative molecular mass (M(r)) of 20.955 +/- 5. This mass is significantly different from that calculated from the published sequence (M(r) 20.894) (White HE et al., 1989, J Mol Biol 207:217-235). Further, ES-MS analysis of the protein after it had been reduced and carboxymethylated indicated the presence of five cysteine residues, whereas the published sequence contains six (Kilby GW et al., 1995, Eur Mass Spectrom 1:203-208). The entire protein sequence of gamma E crystallin has therefore been studied via a combination of ES-MS, ES-MS/MS, and Edman amino acid sequencing. The corrected sequence gives an M(r) of 20.955.3, which matches that obtained by ES-MS analysis of the purified native protein. The corrected sequence is also in agreement with a recent cDNA sequence obtained for a bovine gamma-crystallin by R. Hay (pers. comm.).

Amino Acid Sequence↗

Does vitamin C cause hemolysis in premature newborn infants? Results of a multicenter double-blind, randomized, controlled trial.

OBJECTIVE: We tested the hypothesis that vitamin C supplementation of premature neonates is associated with hemolysis. STUDY DESIGN: A double-blind, randomized, controlled trial of vitamin C supplementation (50 mg/day) was undertaken in premature neonates (birth weight, 1000 to 1500 gm). Infants were randomly assigned to receive vitamin C (Ce-Vi-Sol) (n = 32) or placebo (n = 24) for 14 days. Twenty-three subjects per group were required to detect a difference of 1 SD in corrected carboxyhemoglobin values (alpha = 0.05, beta = 0.10). RESULTS: Day 14 vitamin C levels were lower in control subjects than in supplemented neonates (62 +/- 24 vs 125 +/- 62 micromol/L, p = 0.005). There was no difference in corrected blood carboxyhemoglogin concentrations (0.72 +/- 0.44 vs 0.72 +/- 0.23%; p = 0.95), other parameters of hemolysis, weight gain, blood sampled, presumed septic episodes, necrotizing enterocolitis, feeding intolerance, or transfusion. On day 14, bilirubin values were higher in control subjects than in the supplemented group (77 +/- 37 vs 55 +/- 33 micromol/L; p = 0.04). When a distant outlier in the nonsupplemented group was excluded (163 micromol/L), statistical significance was lost (73 +/- 32 vs 55 +/- 33 micromol/L; p = 0.09). CONCLUSION: Oral supplementation of premature infants with vitamin C is not associated with evidence of increased erythrocyte destruction, hyperbilirubinemia, or other morbidity.

Anemia, Hemolytic↗

Time-limited psychotherapy with Operation Desert Storm veterans.

Time-limited psychotherapy conducted 2 to 9 months after demobilization was evaluated with Persian Gulf Theater veterans of Operation Desert Storm (ODS). Thirty five treatment-seeking veterans were contrasted with 20 non-treatment-seeking ODS Persian Gulf veterans in a repeated measures design at pretest, posttest, and 6-week followup assessments. In addition, psychotherapy participants at followup were contrasted with 80 non-treatment-seeking ODS Persian Gulf veterans from the same military units who were assessed one time at a comparable time point. Time-limited psychotherapy was associated with sustained improved psychosocial functioning and reduced levels of psychiatric and stress-related symptomatology.

Adaptation, Psychological↗

The tammar wallaby: a model to study putative autocrine-induced changes in milk composition.

The marsupial newborn is immature and the mother has the capacity to alter milk composition significantly during lactation, presumably to meet the nutritional requirements of the developing young. Furthermore, macropodid marsupials may practice asynchronous concurrent lactation (ACL)7 whereby the mother provides milk which differs in all the major components from adjacent mammary glands for two young of different ages. This phenomenon suggests that local regulation of mammary function, in addition to endocrine stimuli, is likely to be important for controlling milk composition. This paper explores the possibility that changes in sucking patterns of the young represent the first step in a mechanism to signal the mammary gland for putative autocrine-induced changes in milk composition.

Amino Acid Sequence↗

Developmental and social influences on young girls' early problem behavior.

A developing body of research suggests that there are few sex differences in the rate and severity of problem behavior in early childhood, but clear sex differences emerge at about 4 years of age. The authors explore 2 hypotheses to further the understanding of emerging sex differences in problem behavior across the first 5 years of life. The first posits that the change in girls' problem behavior from infancy to school entry represents a channeling of early problem behavior into predominantly internalizing problems as a result of socialization. The second hypothesis is that the change in girls' early problem behavior during the preschool period results from the more rapid biological, cognitive, and social-emotional development of girls relative to boys. The authors review research on the influence of parents, teachers, and peers on girls' behavior from infancy to preschool regarding the first hypothesis, whereas they review studies of sex differences in developmental processes to test the second. They find moderate support for both hypotheses and present a comprehensive theory of girls' developmental psychopathology that integrates social and developmental influences.

Child↗