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Biomedical subjects

R Young

Publications and source records attributed to R Young.

At least 109 records · Page 6Linked to original sources
PubMed1997

Hydroxyurea-related ankle ulcers in patients with myeloproliferative disorders: a case report and review of the literature.

The association of ankle ulcer development with hydroxyurea therapy in patients with myeloproliferative disorders has been reported in two small case series and two patient reports. It is thought that hydroxyurea, an antineoplastic agent with selective cytotoxicity for cells that divide most actively (such as those of the skin), causes these ulcerations through impairment of normal wound healing in areas of common trauma. Treatment modalities reported include discontinuation of medication, debridement, and topical antibiotics. We report the successful split-thickness skin grafting of a hydroxyurea-related ankle ulceration after preoperative discontinuation of hydroxyurea treatment in a patient with chronic myelogenous leukemia who had previously failed grafting while taking this medication. It is hoped that heightened awareness of the link between hydroxyurea and chronic, debilitating ankle ulcerations in patients with myeloproliferative disorders, as well as familiarity with reported treatments, will promote early diagnosis and aggressive management of these unique and relatively uncommon lesions.

Ankle↗
PubMed1997

Introduction of 6-mercaptopurine in Crohn's disease patients during the perioperative period: a preliminary evaluation of recurrence of disease.

BACKGROUND: Recurrence of Crohn's disease after surgery is a common occurrence, pointing to the need for a strategy to prevent recurrent disease. We report the postoperative course of 10 patients who required intestinal resections for complications related to Crohn's disease. METHODS: All patients had a Pediatric Crohn's Disease Activity Index score of 10 or greater. Among these patients, 5 began treatment with 6-mercaptopurine in the perioperative period. All 10 had received various combinations of prednisone and salicylate compounds. Patients who were given 6-mercaptopurine did not discontinue the medication until 2 years after the surgery. RESULTS: To date, none of the five patients who were placed on 6-mercaptopurine have had recurrence of their Crohn's disease (mean disease-free period 32.6 +/- 18.4 months). Among those five patients not receiving 6-mercaptopurine there have been three relapses (mean time to relapse 3.7 +/- 1.2 months). Log-rank sum analyses of Kaplan-Meier survival curves show benefit to patients receiving 6-mercaptopurine in preventing relapses after intestinal resection (p < 0.05). CONCLUSIONS: Although the underlying pathophysiologic reasons leading to the high relapse rate after intestinal surgery in Crohn's disease are unknown, we conclude that treatment with 6-mercaptopurine in the perioperative period may be warranted to help prevent the recurrence of Crohn's disease after surgery.

Adolescent↗
PubMed1997

Gastroenteric inflammation in children with ulcerative colitis.

This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.

Adolescent↗
PubMed1997

Practical cryosurgery.

Cryosurgery is a widely used modality for the treatment of superficial cutaneous lesions. It can be used for the treatment of benign, premalignant and malignant skin conditions.

Australia↗
PubMed1996

Prostaglandin F2 alpha stimulates hypertrophic growth of cultured neonatal rat ventricular myocytes.

Prostaglandin F2 alpha (PGF2 alpha) stimulates protein synthesis of skeletal and smooth muscle cells in culture and is elevated in the heart during compensatory growth. We hypothesized that PGF2 alpha stimulates hypertrophic growth of neonatal rat cardiac myocytes. Prostaglandin F2 alpha increased [3H]phenylalanine incorporation by cultured ventricular myocytes in a dose-dependent manner (EC50 = 11 nM), suggesting action through a PGF-specific receptor. Semiquantitative reverse transcriptase polymerase chain reaction revealed that PGF receptor mRNA is expressed in ventricular myocytes > A7R5 vascular smooth muscle cells >> cardiac fibroblast-like cells. The protein content of cardiomyocyte cultures was increased by 10 nM PGF2 alpha and 11 beta-PGF2 alpha but was unchanged by 10 nM PGD2, PGE2, PGF1 alpha, carbaprostacyclin, U-46619, or 12- or 15-hydroxyeicosatrienoic acid. Stimulation of myofibrillar gene expression by PGF2 alpha was demonstrated by Northern and Western blot analysis for myosin light chain-2 (MLC-2) and by transient transfection experiments with MLC-2 luciferase expression plasmids. In addition, myofibrillogenesis was increased by PGF2 alpha as assessed by immunocytochemical staining with MLC-2 antisera. Prostaglandin F2 alpha did not affect myocyte proliferation or [3H]thymidine incorporation, thus myocyte growth occurred by hypertrophy. Proliferative and hypertrophic growth of cardiac fibroblast-like cells were unaffected by PGF2 alpha. We conclude that PFG2 alpha stimulates hypertrophic growth of neonatal rat ventricular myocytes in culture and speculate that PGF2 alpha plays a role in myocardial adaptation to chronic hypertrophic stimuli, recovery from injury, and cardiac ontogeny.

Animals↗
PubMed1996

The household context for women's health care decisions: impacts of U.K. policy changes.

Since the Conservatives came to government in 1979 the policy climate generally in the U.K. has been one of the privatization of public provision and tighter controls on public spending. A re-positioning of health and social care has taken place in the light of this pre-eminence of market forces with the assumption increasingly being made that potential service users operate on a "level playing field' of opportunity. A major consequence has been the expansion of household health responsibilities through measures which include a greater emphasis on preventative screening and healthy lifestyles and a general shift in the locus of care to the "community'. Not only has the last decade seen this intensification of pressure on women in their social role as family carers, a restructuring has taken place of the U.K. labour market such that the "double burden' of paid and unpaid work is an increasingly common experience. Contrary to the policy view of equality of access, in-depth interview evidence from Liverpool shows that the health care behaviour of many women is increasingly constrained by their social roles and availability of economic and social network resources. This paper distinguishes between groups who are and are not well equipped to cope in the light of changing structures of provision and discusses the implications of the research for the design and implementation of health and social care.

Cost of Illness↗
PubMed1996

Normative data stratified by age and education for the Neuropsychological Screening Battery for Hispanics (NeSBHIS): Initial report.

Neuropsychological assessment of monolingual Spanish-speaking people in the United States is both a common practice and an ethical dilemma. Lack of appropriate tests, the absence of norms, use of interpreters, and the multiplicity of in-house translations of commonly used measures add to the problem of accurate assessment. This paper helps address the lack of appropriate measures for the neuropsychological assessment of Latinos in the United States by providing a standardization of the Neuropsychological Screening Battery for Hispanics (NeSBHIS). Normative data on a sample of 300 Hispanic subjects stratified by gender, age, and education are provided. Current results reveal that not one measure of cognitive functioning is free from education effects. Both nonverbal measures and psychomotor speed measures were highly related to education. Age effects were noted on measures of psychomotor speed, visuospatial reasoning, and visuoconstructive skills. Gender effects were found on measures of psychomotor speed and language, with males achieving higher scores than females. The limitations of the current findings are considered. Further research for the validation of the NeSBHIS with clinical populations, as well as further normative data collection at the national and international levels, is needed.

Adolescent↗
PubMed1996

Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective, population-based study.

1. Age-related bone loss is well established but reported rates of bone loss in the spine and femur vary widely. The aim of the present study was to investigate changes in bone mineral density in the lumbar spine and proximal femur in healthy postmenopausal women. 2. One hundred and thirty-eight population-based women, aged 45-65 years, recruited from general practice registers in 1990, were assessed at baseline; 108 returned for repeat assessment 4 years later, of whom 31 had taken hormone replacement therapy for 12 months or more of the 4-year study period. Bone densitometry of the lumbar spine and proximal femur was performed by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D and oestradiol were measured by RIA and serum intact parathyroid hormone by radio-immunometric assay. 3. The mean age at follow-up was 62 years (mean of 13.6 years after menopause). Lumbar spine bone mineral density was significantly higher in women who had received hormone replacement therapy for more than 12 months during the study period than in those who had not (P < 0.01). There was no difference between these two groups in the femoral neck or trochanteric bone mineral density. In the lumbar spine, the annual change in bone mass in untreated women was -0.39% (95% confidence intervals -0.60 to -0.09; P < 0.02) whereas there was a small gain in women receiving hormone replacement therapy [+0.36% (-0.12 to 0.84; P not significant)]. The annual change in bone mass in the femoral neck and trochanter was -0.51 and -0.45 respectively in untreated women (P < 0.01 and P < 0.02), and -0.16 and -0.15 in those receiving hormone replacement therapy (P not significant). 4. Our results demonstrate relatively low rates of bone loss in the spine and proximal femur in these healthy, population-based peri- and postmenopausal women. Hormone replacement therapy appeared to be associated with a significant protective effect on spinal, but not femoral, bone mineral density.

Absorptiometry, Photon↗
PubMed1996

Two beginnings for a single purpose: the dual-start holins in the regulation of phage lysis.

For most large phages of both Gram-positive and Gram-negative bacteria, there appears to be a single pathway for achieving disruption of the host envelope, requiring at least two phage-encoded lysis functions (a holin and an endolysin). The holin is a small membrane protein which causes a non-specific lesion in the cytoplasmic membrane, which allows the endolysin to gain access to its substrate, the peptidoglycan. The scheduling of host lysis is effected by regulatory mechanisms which govern the synthesis and activity of the holin protein accumulating in the membrane. Accordingly, aspects of expression and function of holin genes are considered here, focusing mainly on the lambdoid S genes. This group of genes, of which lambda S is the prototype, are characterized by a dual-start motif consisting of two Met start codons separated by one or two codons, at least one of which specifies Arg or Lys. Two protein products are elaborated, differing only by two or three N-terminal residues but apparently possessing opposing functions: the shorter polypeptide is the active holin, or lysiseffector, whereas the longer polypeptide apparently acts as an inhibitor of holin function. Models will be considered which may account for the ability of the holin to form a 'hole' in the cytoplasmic membrane at a programmed time, as well as for the inhibitory properties of the longer product. Finally, we discuss recent results suggesting that the dual-start motif can be viewed as a level of regulation superimposed on a timing function intrinsic to the canonical holin structure.

Amino Acid Sequence↗
PubMed1996

Antigenicity of bovine papillomavirus type 1 (BPV-1) L1 virus-like particles compared with that of intact BPV-1 virions.

Virus-like-particles (VLPs) of various papillomavirus (PV) types have been produced by expressing recombinant L1 proteins in eukaryotic cells. Although VLPs have the same ultrastructural appearance as native virions and their immunogenicity appears to be similar, their antigenicity has not been carefully evaluated. For this reason, the antigenicity of intact bovine PV type 1 (BPV-1) virions was compared with that of BPV-1 recombinant L1 VLPs by ELISA using a well-characterized panel of polyclonal and monoclonal antibodies generated against intact and denatured BPV-1 particles. The structural integrity of the authentic virions and recombinant VLPs was verified by electron microscopy. The specificity of antibodies raised against intact BPV-1 virions and their reactivity with VLPs revealed that the immunodominant, type-specific, conformational epitopes of intact virions were reproduced on VLPs. However, many monoclonal antibodies that define cross-reactive, non-conformational (linear) epitopes cryptic to the authentic BPV-1 virion tested positively when reacted with intact VLPs. One monoclonal antibody, which recognizes a BPV-1 and deer PV surface conformational epitope, did not react with VLPs. Therefore, although VLPs can be used to immunize animals against infection, the external exposure of broadly cross-reactive epitopes of intact L1 VLPs suggests that the use of L1 VLPs in antigenicity studies such as serological screening should be done with caution.

Animals↗
PubMed1996

Mechanisms contributing to pulsus alternans in pressure-overload cardiac hypertrophy.

The mechanisms underlying pulsus alternans in pressure-over-load (POL) cardiac hypertrophy were investigated. Simultaneous measurements of force and intracellular Ca2+ (using fura 2) in right ventricular papillary muscles under conditions that produced mechanical alternans, revealed alternation of the amplitude of the Ca2+ transient together with alternation of force in some POL muscles. Instances when alternation of force occurred without any apparent alternation of the Ca2+ transient were also observed. Exposure of muscles to 5 microM ryanodine significantly attenuated mechanical alternans, thereby implicating a role for the sarcoplasmic reticulum (SR) in this process. The time course of restitution of force and the intracellular Ca2+ transient were, however, unchanged in POL hearts, indicating that SR Ca2+ cycling was not appreciably slowed. The fraction of Ca2+ recirculated intracellularly was derived from studies of postextrasystolic potentiation and was significantly reduced in the POL hearts, suggesting additional differences in cellular Ca2+ regulation. We conclude that changes in Ca2+ handling play an important role in the onset of mechanical alternans in POL hypertrophy, but that additional factors, most likely a slowing of crossbridge cycling rate, are also likely to be important.

Animals↗
PubMed1996

Vertebral deformity in the thoracic spine in post-menopausal women: value of lumbar spine bone density.

Differential bone loss in the thoracic and lumbar spine is known to occur in some patients with osteoporosis. However, the discriminant value of lumbar spine bone densitometry in the detection of thoracic spine fractures in healthy, population-based women has not been established. The relationship between lumbar spine bone mineral density and thoracic spine vertebral deformities in a prospective study of 79 post-menopausal population-based women aged 45-65 years has been investigated. Lumbar spine bone mineral density was measured using dual energy X-ray absorptiometry, and vertebral morphometry was assessed from lateral thoracic spine radiographs. Seven women (9%) were found to have one or more vertebral deformities in the thoracic spine (reduction in anterior or posterior height > 25%). Only one of these had a lumbar spine bone mineral density T score below -2.5, whilst the T score was between -1 and -2.5 in three and greater than -1 in three. Two of these women also had lumbar spine vertebral deformity but lumbar spine radiographs were normal in the remaining five. There were no significant differences in age, height, weight, hormone replacement therapy use or bone mineral density between women with and without thoracic spine fractures. These results demonstrate that vertebral deformities in the thoracic spine occur in a proportion of healthy post-menopausal women in the absence of densitometric or radiographic evidence of osteoporosis in the lumbar spine. Although often asymptomatic, the significance of these fractures lies in the increased risk of further fractures. In the future, morphometric X-ray absorptiometric techniques may prove valuable in the detection of these fractures and avoid the need for conventional radiography.

Absorptiometry, Photon↗
PubMed1996

A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA.

1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) produces an effect in humans that is somewhat similar to both a hallucinogen and a central stimulant. We have previously shown that R(-)-MDA but not S(+)-MDA produces a stimulus effect in animals similar to that of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), whereas S(+)-MDA but not R(-)-MDA produces a stimulus effect similar to that of the stimulant amphetamine. Others have suggested that the stimulus effects of the two MDA isomers may be much more similar than our results would indicate. To help clarify this issue, we have shown that rats (n = 8) can be trained to discriminate 1.25 mg/kg of R(-)-MDA (ED50 = 0.99 mg/kg) from 1.25 mg/kg of S(+)-MDA (ED50 = 0.80 mg/kg) versus 0.9% saline with use of a three-lever operant procedure. To accomplish this task it was necessary to institute a separation of 4 days between injections of the isomers. In tests of stimulus substitution, the administration of various doses of DOM (ED50 = 0.47 mg/kg), S(+)-DOM (ED50 = 2.23 mg/kg) and mescaline (ED50 = 16.04 mg/kg) produced dose-related responding on the R(-)-MDA-appropriate lever. In contrast, the injection of various doses of S(+)-amphetamine (ED50 = 0.46 mg/kg) and cocaine (ED50 = 6.40 mg/kg) produced dose-related responding on the S(+)-MDA-appropriate lever. The administration of racemic MDA, at twice the isomer training dose, resulted in the animals dividing their responses closely between the R(-)-MDA- and S(+)-MDA-designated levers. In antagonism tests, the serotonin-2 antagonist pirenperone blocked the stimulus effect of 1.25 mg/kg of R(-)-MDA but had no effect on the stimulus effect of 1.25 mg/kg of S(+)-MDA. Taken together, these data support the contention that each optical isomer of MDA can produce a markedly different stimulus effect.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

Hormonal status affects the reactivity of the cerebral vasculature.

OBJECTIVE: We compared the blood velocity and vascular resistance in the central retinal and ophthalmic arteries in healthy nonpregnant, pregnant, and postmenopausal women (before and after estrogen replacement therapy). STUDY DESIGN: Color flow Doppler ultrasonography was used to determine systolic, diastolic, and mean velocity, as well as the resistance index in the central retinal and ophthalmic arteries in 10 nonpregnant women, 10 third-trimester pregnant women, and 10 hypoestrogenic postmenopausal women. The postmenopausal patients were again studied 2 months after starting daily oral therapy with 2 mg of micronized 17 beta-estradiol. RESULTS: Pregnant women had a significantly (p < 0.05) higher diastolic blood velocity (4.2 +/- 0.8 cm/sec) and a lower resistance index (0.56 +/- 0.05) in the central retinal artery, when compared with nonpregnant women (diastolic velocity 2.8 +/- 0.8 cm/sec, resistance index 0.68 +/- 0.1), and hypoestrogenic postmenopausal women (diastolic velocity 2.6 +/- 0.9 cm/sec, resistance index 0.73 +/- 0.08). Significant differences were not seen in the ophthalmic artery. In the postmenopausal patients estradiol therapy was associated with an increase in diastolic velocity (2.6 +/- 0.9 cm/sec vs 4.1 +/- 1.6 cm/sec) and a decrease in the resistance index (0.73 +/- 0.08 vs 0.66 +/- 0.1) in the central retinal artery but not in the ophthalmic artery. CONCLUSIONS: The blood velocity and vascular resistance in the cerebral microcirculation appear to change according to the phases of a woman's reproductive life. This may be related, in part, to estrogen levels, because estradiol vasodilates small-diameter cerebral vessels in hypoestrogenic postmenopausal women.

Adult↗
PubMed1995

Methcathione ("cat"): an enantiomeric potency comparison.

With regard to its chemical structure, methcathinone is to cathinone what methamphetamine is to amphetamine. Although it is a drug of abuse outside the United States, methcathione is only recently making an appearance on the clandestine market in this country and has just been classified a Schedule I substance under the Emergency Scheduling Act. We have previously demonstrated that racemic methcathinone produces locomotor stimulation in mice, and substitutes for cocaine and (+)amphetamine in rats trained to discriminate either cocaine or (+)amphetamine, respectively, from saline in tests of stimulus generalization. Because an enantiomeric potency comparison has never been reported for the optical isomers of methcathinone, in the present investigation we synthesized samples of S(-)- and R(+)methcathinone and compared them for their ability: a) to produce locomotor stimulation in mice, b) to elicit cocaine-like responding in rats trained to discriminate 8.0 mg/kg of cocaine from saline vehicle, and c) to elicit (+)-amphetamine-appropriate responding in rats trained to discriminate 1.0 mg/kg of (+)amphetamine from saline vehicle. S(-)Methcathinone was about twice as potent as S(+)amphetamine and three to five times more potent than R(+)methcathinone in the three pharmacologic assays. We conclude that both optical isomers possess central stimulant character, but that S(-)methcathinone is somewhat more potent than R(+)methcathinone.

Animals↗