Search PubMed⌕ Search

Biomedical subjects

J Young

Publications and source records attributed to J Young.

At least 289 records · Page 16Linked to original sources
PubMed1995

Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group.

BACKGROUND: The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure. METHODS AND RESULTS: A multicenter, placebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in patients with symptomatic heart failure and impaired left ventricular function (ejection fraction < 40%). Invasive 24-hour hemodynamic assessment was performed after the first dose and after 12 weeks of treatment. Clinical status and tolerability of treatment with losartan over the 12-week period were also evaluated. One hundred fifty-four patients were enrolled, of which 134 met the protocol criterion of baseline pulmonary capillary wedge pressure > or = 13 mm Hg. During short-term administration, systemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne.s-1.cm-5 at 4 hours) and blood pressure fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment, similar effects were seen on SVR and blood pressure (maximal fall in SVR against placebo, 318 dyne.s-1.cm-5 at 5 hours with 50 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was lower with all active treatment groups. Active treatment was well tolerated, and excess cough was not reported. CONCLUSIONS: This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.

Aged↗
PubMed1995

An Alu VpA marker on chromosome I demonstrates that replication errors manifest at the adenoma-carcinoma transition in sporadic colorectal tumors.

Widespread mutations in simple tandemly repeated (STR) DNA sequences are frequently found in colorectal tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and less frequently in sporadic colorectal cancers. This aims of this study were to determine the type of DNA sequence most commonly affected by such mutations and to examine the point in the natural history of the tumor where replication errors (RERs) appear. An unselected series of colorectal tumors (49 adenomas and 108 carcinomas) was examined with 4 different STR markers: one Alu VpA polymorphism (MYCLI), one tetranucleotide repeat (D17S846), one dinucleotide repeat (D3S1029), and one polyA repeat (AP delta 3 delta). All 3 positive adenomas and 18 of 20 positive carcinomas showed replication errors in the Alu VpA sequence at the MYCLI locus, making this marker more than twice as sensitive as the best of the other 3 markers. Importantly, all positive adenomas showed small foci of carcinoma in situ. This suggests that replication errors manifest at the adenoma/carcinoma transition in sporadic colorectal tumors.

Adenoma↗
PubMed1995

Infection of a subclavian venous stent in a hemodialysis patient.

Endovascular stent placement to prevent restenosis after angioplasty is being increasingly employed. A 63-year-old hemodialysis patient with a right forearm gortex graft developed ipsilateral arm edema, and a right subclavian vein stenosis was diagnosed. This vascular stenosis was presumably secondary to previous placement of temporary access catheters. The subclavian vein stenosis was treated with angioplasty, endovascular stenting, and warfarin, which resulted in resolution of the arm edema. Three weeks after stenting, the patient developed fever to 104 degrees F, chills, and right arm and shoulder edema. All blood cultures grew Staphylococcus aureus, and an Indium-labeled white blood cell scan was positive at the sight of the subclavian stent. Infectious disease consultants recommended urgent removal of the infected stent, but the extensive surgery required posed considerable risk of major morbidity. We elected to conservatively treat the patient. With loss of all upper-extremity access sites, the patient was converted to peritoneal dialysis. Despite the patient's ambulatory status, a femoral venous Hickman catheter was placed and tunneled through the abdominal subcutaneous soft tissue. The patient received 9 weeks of antibiotics by the Hickman catheter with an infusion pump, and warfarin was continued. There has been complete clinical resolution of infection and subclavian thrombosis. Endovascular stents are being used more commonly, and this is the first description, to our knowledge, of a stent infection. The stent infection was successfully managed without surgical removal.

Bacteremia↗
PubMed1995

Biosynthesis and assay of neurosteroids in rats and mice: functional correlates.

Pregnenolone (PREG), synthesized de novo in rodent brain, is the precursor of PREG sulfate (S) and progesterone (PROG). PROG is further converted to 5 alpha-pregnane 3, 20-dione (DH PROG) and to 3 alpha-hydroxy-5 alpha-pregnan-20-one (TH PROG). PROG, DH PROG and TH PROG have been measured in the brain of male and female rats. Neither PROG nor DH PROG disappeared from brain, contrary to plasma, after combined adrenalectomy (ADX) and gonadectomy (CX). Trilostane decreased PROG and increased PREG in the brain of CX+ADX rats and mice, in accordance with a precursor to product relationship. As previously described in CX male mice, the neurosteroid DHEA and its analog 3 beta-methyl-androst-5-en-17-one (CH3-DHEA) inhibited the aggressive behavior of female mice towards lactating female intruders. The decrease of biting attacks by DHEA was definitely more prominent in females neonatally imprinted with testosterone. The degree of inhibition of aggressive behavior was related to the decrease of PREG S concentrations in brain. The memory-enhancing effects of DHEA S and PREG S in male mice have been previously documented. Infusion of PREG S (12 fmol) into the nucleus basalis magnocellularis (NBM) of the rat after the acquisition trial enhanced memory performance in a two-trial recognition task (TTRT). Conversely, TH PROG (6 fmol), which potentiates GABAergic neurotransmission, disrupted performance when injected before the acquisition trial. Accordingly, we have found a positive correlation between the performances of 2-year-old rats in the TTRT and the concentrations of PREG S in the hippocampus, namely animals which performed best had the highest steroid levels.

Adrenalectomy↗
PubMed1995

Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region.

Allelic loss is a common mechanism of inactivation of tumour-suppressor genes in colorectal carcinomas. A number of known or putative tumour-suppressor genes including NF1, BRCA1, NME1, NME2 and prohibitin are present on the long arm of chromosome 17, and this region has not been extensively analysed in colorectal tumours. In this study 72 colorectal carcinomas were examined for allelic loss at eight loci on chromosome 17. Allelic loss was frequent both at the p53 locus, which is known to be important in colorectal carcinoma, and also telomeric to p53 on 17p. Allelic loss continued to be present in more than 50% of cases in the pericentromeric region and on proximal 17q to the marker LEW101 (D17S40) at 17q22-23. The most telomeric markers on 17q showed lower rates of allelic loss. Analysis of cases with partial deletions which did not include the p53 locus showed a common region of overlap of the deletions centred on D17S40. This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this region.

Alleles↗
PubMed1995

A model for understanding gene regulation during spermatogenesis: the mouse testis Pdha-2 promoter.

Spermatogenesis is a complex process requiring the coordinate expression of a number of testis-specific genes. How these genes are regulated during spermatogenesis is poorly understood. However, the elucidation of these mechanisms has significant implications for both medicine and the primary livestock industry. The delineation of this process is of particular interest and, in this study, Pdha-2, a gene which codes for the murine testis-specific isoform of the E1 alpha subunit of the pyruvate dehydrogenase complex, has been used as a model. This review focuses on current knowledge about its expression and regulation during spermatogenesis.

Animals↗
PubMed1995

The design and physical characteristics of a small animal positron emission tomograph.

A small diameter positron emission tomography, designed specifically for small animal studies, was constructed from existing, commercially available, bismuth germanate (BGO) detectors and electronics. The scanner consists of 16 BGO detector blocks arranged to give a tomograph with a diameter of 115 mm and an axial field of view (FOV) of 50 mm. Each block is cut to produce eight (axial) by seven (radial) individual detector elements. The absence of interplane septa enables the acquisition of 3D data sets consisting of 64 sinograms. A 2D data set of 15 sinograms, consisting of eight direct and seven adjacent cross planes, can be extracted from the 3D data set. Images are reconstructed from the 2D sinograms using a conventional filtered backprojection algorithm. Two methods of normalization were investigated, based on either a rotating 68Ge rod source, or a uniform 68Ge plane source, with a uniform cylindrical 18F phantom. Attenuation of the emitted photons was estimated using a rotating 68Ge rod source. The transaxial resolution of the tomograph was measured as 2.3 mm full width at half maximum (FWHM) and 5.6 mm full width at tenth maximum (FWTM) at the centre of the FOV, degrading to 6.6 mm (radial) and 4.4 mm (tangential) FWHM and 10.4 mm (radial) and 14.4 mm (tangential) FWTM at 40.0 mm from the centre of the FOV. The axial slice width was 4.3 mm FWHM, 10.3 mm FWTM at the centre of the transaxial field of view and 4.4 mm FWHM, 10.6 mm FWTM at 20.0 mm from the centre of the FOV. A scatter fraction of 31.0% was measured at 250-850 keV, for an 18F line source centred in a 60 mm diameter, water-filled phantom, reducing to 20.4% and 13.8% as the lower energy discrimination was increased to 380 keV and 450 keV, respectively. The count rate performance was measured using a noise equivalent count rate method, and the linearity of the dead time correction was confirmed over the count rates encountered during routine scanning. In 2D mode, the absolute sensitivity of the tomograph was measured as 9948 counts s-1 MBq-1 at 250-850 keV, 8284 counts s-1 MBq-1 at 380-850 keV and 6280 counts s-1 MBq-1 at 450-850 keV.

Animals↗
PubMed1995

Hospital- and home-based rehabilitation after discharge from hospital for stroke patients: analysis of two trials.

We examined the methodology and results of two previously published randomized controlled trials of home- and hospital-based rehabilitation for stroke patients after discharge from hospital in Bradford and Nottingham, in view of apparently discrepant findings in the two trials. In an analysis of the combined findings of both studies, there was little difference in terms of efficacy between home- and hospital-based care, but a small advantage in favour of home therapy was found in reducing disability between hospital discharge and 6 months. Contrary to an earlier report, we did not find a differential effect of treatment between those who were and those who were not frail. We conclude that home therapy is the method of stroke after-care of choice in urban settings in the UK, although this conclusion may not apply in other health-care settings and further studies are required.

Activities of Daily Living↗
PubMed1995

Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset.

The M1 member of the Mu subclass of glutathione S-transferase (GSTM1) is only expressed in about 50% of individuals. In contrast, GSTT1, a member of the theta class which has been recently shown to be polymorphic, is expressed in 85% of Australian individuals. Previous studies have shown a significant excess of homozygous null GSTM1 genotypes among individuals with colorectal cancer, particularly those with proximal tumours. This suggests that GSTM1 plays a role in susceptibility to this neoplasm. In this study of 132 individuals with colorectal cancer and 200 controls, no significant excess of GSTM1 homozygous null genotypes was found among colorectal cancer patients with either a proximal or distal tumour. This suggests that the association between GSTM1 homozygous null genotypes and colorectal cancer is of smaller effect than has been reported previously using larger sample sizes. We have also examined the frequency of homozygous null GSTT1 genotypes in patients with colorectal cancer. Although the frequency was not significantly different in cases compared to control individuals, GSTT1 null homozygotes were significantly more common in patients who were diagnosed before the age of 70 years than in those who were diagnosed at an older age. This suggests that the GSTT1 genotype, and perhaps also the GSTM1 genotype for which a similar, but non-significant effect was seen, might influence the age of onset of colorectal cancer.

Adenocarcinoma↗
PubMed1995

Prevalence and associated features of the cold hemiplegic arm.

BACKGROUND AND PURPOSE: Some stroke patients complain of an unpleasant sensation of coldness in the hemiplegic arm. This study aimed to determine the prevalence of this symptom and any associated features. METHODS: A questionnaire about symptoms in the arms was sent to patients at least 12 months after stroke. Reflex sympathetic dystrophy (RSD) was diagnosed if four typical symptoms were present in the arm. RESULTS: One hundred patients were recruited and 75 complete replies received. The mean age of the patients was 74 years, and the mean time since the stroke was 19 months. Forty patients (53%) experienced unilateral coldness in the hemiplegic arm. In 14 this sensation was constant, and 10 rated the symptom as troublesome. The symptom developed at a median time of 1 month after stroke, but only 13 patients (32%) sought advice from a doctor. Sensory symptoms and arm and shoulder pain were common, but the only symptoms associated with coldness were numbness (P < .001) and color change (P < .05). Fifteen patients fulfilled the diagnostic criteria for RSD, 13 of whom had coldness only in the hemiplegic arm. CONCLUSIONS: A sensation of coldness in the hemiplegic arm is common and distressing. It is associated with numbness and color changes in the arm. Some cases are caused by RSD, but other patients have coldness that may be due to other causes such as a vasomotor abnormality.

Aged↗
PubMed1995

Intrapleural administration of vitreous high duty ceramic fibres and heated devitrified ceramic fibres does not give rise to pleural mesothelioma in rats.

In order to determine whether they are potentially carcinogenic to the pleural mesothelium, three samples of ceramic fibre have been administered to rats by the intrapleural route. These samples were a high-duty grade refractory ceramic fibre (manufactured by Thermal Ceramics Ltd) in the as-manufactured vitreous state and two devitrified samples produced by heating the same fibre for 2 weeks at 1200 degrees C and for two weeks at 1400 degrees C. The mean lifespans of the groups of rats treated with vitrified and devitrified ceramic fibres were not significantly different from that of the control rats. In these studies none of the treated or control rats developed pleural mesothelioma, making it unlikely that ceramic fibres of this type, whether vitreous or devitrified, are potentially carcinogenic to the pleural mesothelium.

Animals↗
PubMed1995

Even after priming with ovarian steroids or pulsatile gonadotropin-releasing hormone administration, naltrexone is unable to induce ovulation in women with functional hypothalamic amenorrhea.

In functional hypothalamic amenorrhea (HA), it has been reported that administration of opioid receptor antagonists restores gonadotropin secretion and ovarian function. However, endogenous opioids may modulate gonadotropin secretion only in the presence of ovarian steroids. To further study these conflicting results, a group of nine women with secondary functional HA who wished to become pregnant were studied. The opiate antagonist naltrexone (Nal; 100 mg/day) was administered for two 30-day periods, starting on either day 22 (Nal 1) of a well characterized replacement regimen with estradiol (E2) and progesterone (P), or on day 22 (Nal 2) of the luteal phase induced by exogenous pulsatile GnRH administration (10 micrograms/pulse, iv, every 90 min). Plasma LH and FSH were measured every 10 min for 8 h before treatment and on day 12 of each treatment period (Nal 1, pulsatile GnRH, and Nal 2). Ovulation was monitored during each treatment. Plasma E2 levels were measured on days 12 and 22, and P levels on day 22 of each treatment. During exogenous E2 and P administration, plasma steroid levels reached luteal phase levels. However, during Nal 1, plasma E2 levels fell to prestudy levels and remained low. No follicular growth occurred, and the pulsatile study showed pretreatment frequency, amplitude, and mean plasma levels of LH. On day 12 of pulsatile GnRH administration, plasma E2 levels increased, and LH and FSH pulses followed each GnRH pulse during the frequent sampling study. Ovulation occurred in all women during pulsatile GnRH treatment. During Nal 2 treatment, plasma E2 levels returned to prestudy levels without follicular growth, and the pulsatile study was similar to those prior treatment and during Nal 1 administration. In conclusion, Nal, started during priming either with exogenous E2 and P treatment or gonadotropin stimulation induced by pulsatile GnRH administration, was unable when continued alone to initiate or maintain gonadotropin secretion in women with HA. Thus, the exclusive role of opioids in HA and the effect of Nal even in the presence of ovarian steroids are questionable.

Adult↗
PubMed1995

A case of bilateral thalamic lesions with anterograde amnesia and impaired implicit memory.

Thalamic nuclei appear to play an important role in memory functioning. Severe anterograde amnesia has been reported with lesions of the dorsomedial and anterior nuclei and their connections. We report the case of a woman with discrete thalamic lesions involving the anterior and dorsomedial nuclei who had a persistent anterograde amnesia. Contrary to a previous case report describing impairment only with explicit memory, this patient had impairment with both implicit and explicit memory. This case is discussed in terms of the relevant literature associating the diencephalon, amnesia, and implicit memory.

Clinical Conference↗
PubMed1995

Allogeneic bone marrow transplantation for fucosidosis.

Bone marrow transplantation was performed on an 8-month-old boy who was diagnosed as having fucosidosis following the diagnosis of the disease in his older brother. Although he was asymptomatic and his development was normal, abnomalities were found on an MRI scan prior to transplant. In the absence of a suitable related donor, an unrelated volunteer donor was used. Conditioning for the transplant consisted of busulphan and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of in vitro T cell-depletion of the bone marrow and in vivo administration of cyclosporin. The post-transplant period was complicated by moderately severe graft-versus-host disease. Engraftment was documented by the presence of donor levels of alpha-fucosidase, donor blood group and tissue type (difference in the DQ antigen), and chromosomal polymorphism pattern of donor origin. Eighteen months after transplant, there is evidence of mild neurodevelopmental delay. By contrast, his elder sibling showed far greater developmental delay at the same age. The patient's MRI scan shows improvement. We believe this to be the first case of human fucosidosis treated by bone marrow transplantation.

Bone Marrow Transplantation↗