Search PubMed⌕ Search

Biomedical subjects

I Marshall

Publications and source records attributed to I Marshall.

At least 55 records · Page 3Linked to original sources
PubMed1998

Diffusion anisotropy measurements in ischaemic stroke of the human brain.

Magnetic resonance diffusion imaging was performed on 12 patients presenting with symptoms of acute ischaemic stroke (1-6 days post-ictus). Apparent diffusion coefficient (ADC) and diffusion anisotropy measurements were obtained from ischaemic and contralateral normal regions. ADC measurements were decreased by around 40% in ischaemic regions, indicated by an average stroke to normal ratio of 0.56 +/- 0.04 (p < 0.0001). The measured anisotropy was shown to be significantly increased in ischaemic regions, using both standard deviation and volume ratio anisotropy indices, which gave stroke to normal ratios of 1.78 +/- 0.27 (p = 0.003) and 0.87 +/- 0.05 (p = 0.005) respectively. The effects of gradient interactions, image registration, noise contamination and rotational variance and their implications for the results obtained in this study are discussed.

Acute Disease↗
PubMed1998

Leak point pressure use for intraoperative adjustment of the continence mechanism in patients undergoing continent cutaneous urinary diversion.

OBJECTIVES: Failure of the continence mechanism is the most common cause of unsatisfactory results and the need for revision in patients with continent cutaneous urinary diversion. We believed that incontinence in these patients could be eliminated or minimized by using the concept of leak point pressure intraoperatively to make appropriate adjustments and thus ensure adequate continence postoperatively. METHODS: The appropriate ileocolonic bowel segment for continent urinary diversion was isolated. Whenever the appendix was available, the unaltered or minimally altered appendicocolic junction was used for continence. In the absence of an appendix, the tapered distal ileum and reinforced ileocecal valve were used. Intraoperative leak point pressure (pressure at which leakage occurs) was measured before detubularization using a simple standing column manometer and arterial line tubing. Whenever leakage occurred at pressure less than 75 to 80 cm H2O, adjustment of the continence mechanism was performed and leak point pressure measurement was repeated to ensure adequate continence. RESULTS: Seventy-seven patients had long-term follow-up (30 to 100 months). These included 41 in whom the native appendix was used and 36 in whom the terminal ileum and ileocecal valves were used. Adjustment of the continence mechanism was required in 32 of the 41 patients in whom the native appendicocolic junction was used and in all 36 patients in whom the tapered ileum and ileocecal valve were used. After adjustment, all patients attained leak pressures over 80 cm H2O. At the last follow-up visit, all 77 patients were continent on intermittent catheterization every 3.5 to 6 hours. None has required revision of the continence mechanism. CONCLUSIONS: Intraoperative measurement of leak point pressure is valuable in predicting the need for adjusting the continence mechanism and eliminating or substantially minimizing the need for subsequent revision.

Follow-Up Studies↗
PubMed1998

A theoretical study of the effect of experimental noise on the measurement of anisotropy in diffusion imaging.

Diffusion tensor imaging (DTI) is a modality known to be highly sensitive to the detrimental effects of experimental noise. Here, using Monte Carlo simulations, we compare and contrast how noise complicates the measurement of diffusion anisotropy in diffusion tensor and conventional diffusion-weighted imaging (DWI). As the signal-to-noise ratio (SNR) decreases below a value of approximately 20, the eigenvalues (lambda(i)) of the diffusion tensor D are found to diverge rapidly from their true values, with the result that the measured anisotropy can be significantly in error and isotropic structures falsely assigned a high level of anisotropy. The effect of noise on the rotationally variant indices, calculated from a conventional diffusion-weighted imaging experiment, is found to be much less insidious, because the apparent diffusion coefficients (ADCs) diverge only slowly as the signal-to-noise decreases. Thus, although rotationally variant indices almost always underestimate the true diffusion anisotropy, they show only a small susceptibility to experimental noise and hence, are preferred to their rotationally invariant counterparts when the signal-to-noise ratio is small.

Anisotropy↗
PubMed1998

Alpha1A-adrenoceptor mediated contraction of rat prostatic vas deferens and the involvement of ryanodine stores and Ca2+ influx stimulated by diacylglycerol and PKC.

1 The present study has investigated the alpha1-adrenoceptor subtype mediating contraction of the rat isolated prostatic vas deferens and the possible effector mechanisms involved in this response by use of functional experiments. 2 Contractions to noradrenaline in the rat isolated prostatic vas deferens were antagonized by prazosin (9.4, 1.04+/-0.19, pA2 and Schild plot slope), 5-methyl urapidil (8.9, 1.10+/-0.13), BMY 7378 (6.4, 1.53+/-0.07) and RS 17053 (8.3, 1.13+/-0.18). These affinities are consistent with the response being mediated by the alpha1A-adrenoceptor subtype. 3 The contraction to noradrenaline at 37 degrees C consisted of an initial phasic response, composed of many rhythmic contractile spikes and a more slowly developing tonic contraction. When the temperature was lowered to 25 degrees C the phasic contraction became a smooth single response which was increased in magnitude. 4 In Ca2+-free Krebs solution the tonic contraction to noradrenaline (10(-4) M) was abolished, suggesting that this response was dependent on influx of extracellular Ca2+. After 2 min in Ca2+-free Krebs solution at 37 degrees C and 25 degrees C the phasic response to noradrenaline (10(-4) M) was 38+/-2% and 91+/-4%, respectively, compared with the phasic contraction to noradrenaline (10(-4) M in normal Krebs solution) and after 30 min it was abolished at 37 degrees C and was 7+/-1% at 25 degrees C. Ryanodine abolished the noradrenaline response in Ca2+-free Krebs solution for 2 min at 25 degrees C, while cyclopiazonic acid reduced it to 36+/-2%. 5 In normal Krebs solution at 25 degrees C the protein kinase C inhibitor calphostin C reduced the tonic contraction to noradrenaline (10(-5) M) from 36+/-8% to 14+/-3% compared with the phasic contraction to noradrenaline (10(-4) M). The DAG kinase inhibitor R 59022 increased the contraction following the initial phasic response to a maximum of 107+/-17% after 35 s, before dropping down to a well maintained contraction which was still greater in magnitude compared with the control. Nifedipine (3x10(-7) M) reduced the tonic contraction from 49+/-6% to 7+/-1% but did not reduce the phasic response. Ryanodine (10(-4) M) reduced the phasic contraction from 50+/-2% to 7+/-1% and the tonic response from 47+/-5% to 27+/-5%. 6 The phorbol ester phorbol-12,13-dibutyrate at 25 degrees C produced a transient contraction of the rat prostatic vas deferens, maximum response (10(-5) M) 48+/-4%, compared with the maximum tonic response to noradrenaline. The contraction to PDBu (10(-5) M) was reduced to 23+/-2% by calphostin C (10(-6) M) and to 15+/-1% by nifedipine (3x10(-7) M) and was abolished after 2 min in Ca2+-free Krebs solution. 7 In conclusion, the alpha1A-adrenoceptor mediated contraction to noradrenaline of the rat prostatic vas deferens appears to consist of an initial phasic component due to the release of intracellular Ca2+ from ryanodine-sensitive stores. These stores are depleted in the absence of extracellular Ca2+ and this depletion is slower at 25 degrees C than at 37 degrees C. The phasic contraction is followed by a tonic contraction involving activation of protein kinase C by diacylglycerol and influx of Ca2+ through nifedipine-sensitive channels.

Adrenergic alpha-Agonists↗
PubMed1998

Pharmacological characterization of CGRP receptors mediating relaxation of the rat pulmonary artery and inhibition of twitch responses of the rat vas deferens.

1. CGRP receptors mediating vasorelaxation of the rat isolated pulmonary artery and inhibition of contractions of the rat isolated prostatic vas deferens were investigated using CGRP agonists, homologues and the antagonist CGRP8-37. 2. In the pulmonary artery, human (h)alpha-CGRP-induced relaxation of phenylephrine-evoked tone was abolished either by removal of the endothelium or by NG-nitro-L-arginine (10(-5) M). The inhibitory effect of NG-nitro-L-arginine was stereoselectively reversed by L- but not by D-arginine (10(-4) M). Thus, CGRP acts via nitric oxide released from the endothelium. 3. In the endothelium-intact artery, halpha-CGRP, hbeta-CGRP and human adrenomedullin (10(-10) - 3 x 10(-7) M), dose-dependently relaxed the phenylephrine-induced tone with similar potency. Compared with halpha-CGRP, rat amylin was around 50 fold less potent, while [Cys(ACM2,7)] halpha-CGRP (10(-7) - 10(-4) M) was at least 3000 fold less potent. Salmon calcitonin was inactive (up to 10(-4) M). 4 Human alpha-CGRP8-37 (3 x 10(-7) - 3 x 10(-6) M) antagonized halpha-CGRP (pA2 6.9, Schild plot slope 1.2+/-0.1) and hbeta-CGRP (apparent pKB of 7.1+/-0.1 for halpha-CGRP8-37 10(-6) M) in the pulmonary artery. Human beta-CGRP8-37 (10(-6) M) antagonized halpha-CGRP responses with a similar affinity (apparent pKB 7.1+/-0.1). Human adrenomedullin responses were not inhibited by halpha-CGRP8-37 (10(-6) M). 5. In the prostatic vas deferens, halpha-CGRP, hbeta-CGRP and rat beta-CGRP (10(-10) - 3 x 10(-7) M) concentration-dependently inhibited twitch responses with about equal potency, while rat amylin (10(-8) - 10(-5) M) was around 10 fold less potent and the linear analogue [Cys(ACM2,7)] halpha-CGRP was at least 3000 fold weaker. Salmon calcitonin was inactive (up to 10(-4) M). 6 The antagonist effect of halpha-CGRP8-37 (10(-5) 3 x 10(-5)) in the vas deferens was independent of the agonist, with pA2 values against halpha-CGRP of 6.0 (slope 0.9+/-0.1), against hbeta-CGRP of 5.8 (slope 1.1+/-0.1), and an apparent pKB value of 5.8+/-0.1 against both rat beta-CGRP and rat amylin. Human beta-CGRP8-37 (3 x 10(-5) - 10(-4) M) competitively antagonized halpha-CGRP responses (pA2 5.6, slope 1.1+/-0.2). The inhibitory effect of halpha-CGRP on noradrenaline-induced contractions in both the prostatic and epididymal vas deferens was antagonized by halpha-CGRP8-37 (pA2 5.8 and 5.8, slope 1.0+/-0.2 and 1.0+/-0.3, respectively). 7 The effects of halpha-CGRP and halpha-CGRP8-37 in both rat pulmonary artery and vas deferens were not significantly altered by pretreatment with peptidase inhibitors (amastatin, bestatin, captopril, phosphoramidon and thiorphan, all at 10(-6) M). The weak agonist activity of [Cys(ACM2,7)] halpha-CGRP in the vas deferens was not increased by peptidase inhibitors. 8 These data demonstrate that two different CGRP receptors may exist in the rat pulmonary artery and vas deferens, a CGRP1 receptor subtype in the rat pulmonary artery (CGRP8-37 pA2 6.9), while the lower affinity for CGRP8-37 (pA2 6.0) in the vas deferens is consistent with a CGRP2 receptor.

Animals↗
PubMed1998

Effect of human immigration on the age distribution of schistosome infections in Siavonga community, Lake Kariba, Zambia.

A study on the distribution of schistosomiasis in the community at Siavonga revealed Schistosoma haematobium infection in 35.5% of 338 subjects and a geometric mean egg count (GMEC) and (S.D.) of 13.7 (7.2) eggs/10 ml urine. The prevalence of S. mansoni infection among 323 subjects was 60.1%, with a GMEC of 336.8 (4.8) eggs/g stool. Among the infected, 69.5% carried both schistosome species. Although prevalence of infection with either species was highest in those aged 10-14 years, high prevalences of infection were found in older age groups and egg intensities were uniformly distributed throughout all age-groups. The observed diversion from the typically age-dependent distribution of schistosome infections probably reflects exposure to infection relatively late in life, as the result of immigration from non-endemic areas.

Adolescent↗
PubMed1998

Studies of acute ischemic stroke with proton magnetic resonance spectroscopy: relation between time from onset, neurological deficit, metabolite abnormalities in the infarct, blood flow, and clinical outcome.

BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy (MRS) can be used to study metabolite abnormalities in the brains of stroke patients. We have used it to examine the relations between the metabolites in the infarct (N-acetylaspartate [NAA] and lactate) and the time lapse from stroke to MRS, the presenting neurological deficit, infarct size and swelling (on MRI), blood flow to the infarct (estimated by transcranial Doppler ultrasound), and clinical outcome. METHODS: Patients with symptoms of a moderate to large cortical infarct underwent serial proton MRS (Siemens 1.5 Magnetom) within 4 days, from 5 to 10, and from 11 to 35 days after the stroke. A long echo time PRESS single voxel or chemical shift imaging acquisition was used. Transcranial Doppler ultrasound was performed daily in the first week and twice per week thereafter until the final MRS. Clinical features and baseline demographic data were collected independently by a stroke physician and 6-month outcome by postal questionnaire. RESULTS: Fifty patients underwent at least 1 MRS examination. Reduced NAA in the infarct within the first 4 days was related to the clinical stroke syndrome, more extensive infarction, more severely reduced blood supply to the infarct, and the presence of lactate. The presence of lactate was related to large infarcts and reduced NAA. Swelling in the infarct was most closely associated with large infarcts and reduced blood supply but not reduced NAA or the presence of lactate. Clinical outcome was most closely related to the extent of the infarct (more than to the clinical syndrome)--the larger the infarct the worse the outcome--but not to the metabolite concentrations alone. CONCLUSIONS: The reduction in NAA (but not the presence of lactate) in a visible infarct was related to the reduction in blood flow to the infarct, which in turn was related to infarct extent and clinical outcome.

Acute Disease↗
PubMed1998

Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects.

Around 50% of patients with the sleep apnea/hypopnea syndrome (SAHS) are not obese: body mass index (BMI) < 30 kg/m2. We hypothesized that local fat deposition around the upper airway may be different in nonobese patients with SAHS from that in normal subjects with the same body mass. We therefore examined the relationship between indices of general obesity; BMI, neck circumference (NC), and percentage total body fat with neck fat deposition measured by magnetic resonance imaging in three matched subject groups. Nine nonobese, nonsnoring control subjects (BMI, 25 SE 0.7 kg/m2; NC, 38.1 SE 0.5 cm; age, 37.5 SE 2.5 yr), nine nonobese patients with SAHS (BMI, 25.7 SE 0.4 kg/m2; NC, 39.8 SE 0.8 cm; age, 40 SE 4.2 yr), and nine obese patients with SAHS matched to the other groups for age (BMI, 34 SE 1.1 kg/m2; NC, 43.9 SE 0.6 cm; age, 40 SE 2.7 yr). Neck volume and fat content were assessed from the hard palate to the vocal cords using T1-weighted images. Percentage total body fat was 30 and 44% greater in nonobese and obese patients with SAHS, respectively, than in control subjects. Neck tissue volume was 10% greater in nonobese and 28% greater in obese patients with SAHS than in control subjects. The percentage of neck tissue volume attributed to fat was 27% greater in nonobese and 67% greater in obese patients with SAHS than in control subjects. The excess fat in both the nonobese and obese patients with SAHS compared with that in control subjects was localized to areas anterolateral to the upper airway, the differences were 52 and 88%, respectively. There were no significant differences between nonobese patients with SAHS and control subjects with respect to fat located in other areas of the neck; obese patients with SAHS had 42% more fat than control subjects (p < 0.05). We conclude that even relatively nonobese patients with SAHS have excess fat deposition, especially anterolateral to the upper airway when compared with control subjects with the same level of obesity assessed using BMI and NC. This may contribute to their predisposition to SAHS.

Adipose Tissue↗
PubMed1997

Nucleotide sequence of the Barmah Forest virus genome.

Barmah Forest virus (BFV) is an atypical alphavirus [Dalgarno, L., Short, N. J., Hardy, C. M., Bell, J. R., Strauss, J. H., and Marshall, I. D. (1984). Virology 133, 416-426] and has been classified as the sole known member of a seventh alphavirus serocomplex. The complete nucleotide sequence of BFV genomic RNA is 11,488 nucleotides in length excluding the poly(A) tail. Two long open reading frames in the RNA encode a nonstructural polyprotein of 2411 amino acids and a structural polyprotein of 1239 amino acids, respectively. The BFV envelope protein E2 is unique among sequenced alphaviruses in having no N-linked glycosylation sites; E1 carries two glycosylation sites. From amino acid sequence comparisons with sequenced alphaviruses BFV is most closely related to Ross River and Semliki Forest viruses. Sequence homology between BFV and other alphaviruses is relatively uniform along the length of the nonstructural and structural polyproteins, providing no evidence that BFV has arisen from recombination between ancestral alphaviruses in the coding region of the genome. The BFV 3' noncoding region of 445 nucleotides has unusual features. There are two unrelated sequence blocks of 48 nucleotides (sequence I) and 47 nucleotides (sequence II) both of which are repeated once. Sequence I is closely related to a repeat in the 3' noncoding region of Ross River and Getah viruses; sequence II is unrelated to repeat blocks in other sequenced alphaviruses. Thus, recombination between ancestral viruses may have played a role in the evolution of the BFV 3' noncoding region.

Alphavirus↗
PubMed1997

Use of Voigt lineshape for quantification of in vivo 1H spectra.

Quantification of NMR visible metabolites by spectral modeling usually assumes a Lorentzian or Gaussian lineshape, despite the fact that experimental lineshapes are neither. To minimize systematic fitting errors, a mixed Lorentzian-Gaussian (Voigt) lineshape model was developed. When tested with synthetic FIDs, the Voigt lineshape model gave more accurate results (maximum error 2%) than either Lorentzian (maximum error 20%) or Gaussian models (maximum error 12%). The three lineshape models gave substantially different peak areas in an in vitro experiment, with the Voigt model having a much lower chi2 (2.1 compared with 5.2 for the Lorentzian model and 6.2 for the Gaussian model). In a group of 10 healthy volunteers, fitting of 1H spectra from cerebral white matter gave significantly different peak areas between the methods. Even when area ratios were taken, the Lorentzian model gave higher values (+5% for NAA/choline and +2% for NAA/creatine) than the Voigt lineshape model, whereas the Gaussian model gave lower values (-2% and -1%, respectively).

Brain Chemistry↗
PubMed1997

Calculations and experimental studies of the lineshape of the lactate doublet in PRESS-localized 1H MRS.

Accurate quantification of NMR metabolites by spectral modeling requires assumed lineshape functions. For singlet resonances, a combination of Lorentzian and Gaussian lineshapes is sufficient, but for weekly J-coupled resonances such as lactate, more complex lineshapes are necessary. In this work, the lactate lineshape is calculated for the PRESS sequence using standard RF pulses, and compared with experimental measurements. A similar comparison is made for PRESS-localized spectroscopic imaging, in which the lineshape varies from voxel to voxel across the field of view. These observations have important implications for the quantification of lactate in experimental and human studies.

Computer Simulation↗
PubMed1997

Normalisation of metabolite images in 1H NMR spectroscopic imaging.

Single slice proton magnetic resonance spectroscopic images were taken from a volume of interest (VOI), which was localised using the point resolved spectroscopy (PRESS) sequence. Non-uniformities in the excitation profile of the VOI within the image plane were accounted for using a uniformity correction image. Metabolite images were divided on a voxel-by-voxel basis with a water image obtained from a VOI of the same spatial dimensions from a phantom acquisition. Normalisation procedures carried out on phantom metabolite images were needed to account for the spatial shift in the excitation profile of the VOI, which varies linearly with the chemical shift of the metabolite. Patient metabolite images were then normalised using a VOI water image from a phantom acquisition, which was spatially shifted according to the metabolite chemical shift. In a study of 14 stroke patients, metabolite maps of the distribution of choline, creatine and N-acetyl aspartate (NAA) were constructed. The spectral signal intensities from these metabolites in the infarcted and in the contralateral region were calculated using the raw maps and secondly with the same maps after the B1 normalisation process. In the initial analysis only the metabolite NAA showed a significant decrease, whilst all three metabolites showed a significant reduction in the normalised analysis. These results confirm that normalisation of PRESS localised images does have a significant bearing upon any quantitative measurements made using such images.

Algorithms↗
PubMed1997

Characterization of alpha1-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta, mesenteric artery and pulmonary artery.

1. The subtype of alpha1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned alpha1-adrenoceptor subtypes in binding studies. 2. Cumulative concentration-contraction curves for phenylephrine were competitively antagonized in the rat thoracic aorta by prazosin (pA2 9.9), WB4101 (pA2 9.6), 5-methylurapidil (pA2 8.1), benoxathian (pA2 9.2) and indoramin (pA2 7.4). These compounds were also competitive antagonists in the mesenteric and pulmonary arteries (except for 5-methylurapidil in the pulmonary artery), (prazosin pA2 9.9 and 9.7; WB4101 pA2 9.8 and 9.6; 5-methylurapidil pA2 7.9 and pK(B) estimate 8.0; benoxathian pA2 8.8 and 9.3; indoramin pA2 7.2 and 7.5, respectively). 3. RS 17053 was not a competitive antagonist in any blood vessel as Schild plot slopes were greater than unity. The pK(B) estimates for RS 17053 were 7.1 in aorta, 7.0 in the mesenteric artery and 7.7 in the pulmonary artery. 4. The alpha1D-subtype selective antagonist BMY 7378 appeared to be non-competitive with shallow Schild plot slopes. The data were better fitted with two lines in all tissues, with Schild plot slopes that were no longer different from unity, except in the pulmonary artery. The higher affinity site for BMY 7378 in the aorta had a pA2 of 9.0, while it was 8.8 and 8.9 in the mesenteric and pulmonary arteries, respectively. 5. MDL73005EF acted in a non-competitive manner in all three blood vessels, with shallow Schild plot slopes. The pK(B) estimates for MDL73005EF were 8.4 in aorta, 7.5 in the mesenteric artery and 8.0 in the pulmonary artery. 6. In all three blood vessels the functionally determined antagonist affinity estimates correlated best with published pKi values for their displacement of [3H]-prazosin binding on membranes expressing cloned alpha1d-adrenoceptors compared with alpha1a- or alpha1b-adrenoceptors. The antagonist affinity estimates in the aorta, mesenteric and pulmonary arteries correlated highly with their previously published pA2 values in rat aorta (alpha1D) and less well with those for alpha1A- and alpha1B-adrenoceptors mediating contraction of the rat epididymal vas deferens and rat spleen, respectively. 7. The results of this study suggest that the contraction to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery are mediated in part via the alpha1D-subtype of adrenoceptor. The data for both BMY 7378 and MDL73005EF in all three blood vessels are consistent with receptor heterogeneity. However, the identity of the second site is unclear.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

The effect of age, sex, obesity and posture on upper airway size.

Most patients with sleep apnoea/hypopnoea syndrome (SAHS) are middle-aged men. As there are conflicting data on the effects of age and gender on upper airway calibre, we tested the hypothesis that increasing age and the male sex predispose to upper airway narrowing in normal subjects. We measured upper airway calibre using acoustic reflection in 60 men and 54 women (median 35, range 16-74 yrs) both seated and supine. All upper airway dimensions, except oropharyngeal junction (OPJ), decreased with increasing age in both men and women (r > -0.24, p < or = 0.05) while supine (r2 > 0.06). Men had greater changes in airway area at OPJ on lying down (mean (SEM) 0.5 (0.1), 0.2 (0.1) cm2; p < 0.02). Men had greater body mass indices (mean (SD) 26 (4), 24 (4) kg.m-2; p = 0.04), and larger neck circumferences (mean (SD) 38 (3), 33 (2) cm; p < 0.0001) than women. For any body mass index, neck circumference was larger in men than women (p < 0.001). This study shows that upper airway size decreases with increasing age in both men and women, and that men have greater upper airway collapsibility on lying down at oropharyngeal junction than women.

Aging↗
PubMed1996

Raloxifene analog (LY117018 HCL) ameliorates cyclosporin A-induced osteopenia in oophorectomized rats.

Cyclosporin A (CsA) administered to the oophorectomized (Ox) rat exacerbates the high turnover osteopenia associated with estrogen deficiency. 17 beta-estradiol replacement therapy prevent this bone loss. The aim of this study was to see whether an estrogen-like compound, Raloxifene analog (LY117018 HCL, Ral) could likewise ameliorate CsA-induced osteopenia in the Ox rat. Sixty 6-month-old Sprague-Dawley rats, divided into five groups, underwent oophorectomy. One group acted as a basal group and the others received either vehicle (group B), CsA 15 mg/kg/day (group C), Ral 3 mg/kg/day (group D), or CsA 15 mg/kg/day and Ral 3 mg/kg/day (group E) for 28 days by gavage. A sixth sham operated group of 12 rats received vehicle only (group A). Rats were weighed and bled on days 0, 14, and 28 for measurement of ionized calcium, glucose, osteocalcin (BGP), 17 beta-estradiol, and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Tibiae were removed on day 28 for bone histomorphometry after double tetracycline and calcein labeling. Oophorectomy caused a significant gain in weight in groups B and C which was prevented by Ral in groups D and E. Randomized blood glucose levels and 1,25(OH)2D3 levels were elevated in both CsA-treated groups. Blood ionized calcium levels were lower in vehicle (group B) compared with sham (group A) on day 28. Ox (group B) had significantly higher serum BGP levels compared with sham-operated rats. Serum BGP levels were further elevated in group C compared with vehicle and were lowered in both Ral-treated groups to vehicle levels by day 28. Bone histomorphometry revealed a high turnover osteopenia with increased parameters of bone formation and resorption and loss of cancellous bone volume postoophorectomy (group B). CsA (group C) exacerbated the effects of oophorectomy. Ral (group D) completely prevented the high turnover osteopenia caused by oophorectomy and was able to attenuate substantially the effects of CsA in the Ox rat (group E). Ral therapy ameliorated CsA-induced osteopenia in the Ox rat and might prove a useful agent in preventing bone loss in postmenopausal women receiving CsA.

Animals↗
PubMed1996

Reproducibility of metabolite peak areas in 1H MRS of brain.

We studied the reproducibility of metabolite signals (from N-acetyl aspartate [NAA], choline, and creatine) measured with a standard single-voxel proton magnetic resonance spectroscopy technique (PRESS, TE = 135 ms, 8 ml VOI) in vitro and in two groups of normal volunteers. Spectral peak areas were quantified both by integration and by curve-fitting. In the in vitro study, the "between-days" variability (coefficient of variation [CV]) of measurements ranged from 0.9% to 2.3%. In the first group of volunteers (n = 12), single voxel spectroscopic measurements (8 ml VOI, 256 acquisitions [ACQs]) were made from mirror-image parts of the right and left hemispheres on 2 separate days. The "between-days" CV of measurements ranged from 9% to 18% for metabolite areas, and from 10% to 26% for metabolite area ratios. There were no significant differences between quantification method or hemisphere. After checking and optimising the MR scanner performance (in fact, it was virtually optimal), the second group (n = 4) each had six sequential single voxel spectroscopic measurements (each of 64 ACQs) from the right hemisphere (without moving the voxel) on each of 4 separate days. Even when the metabolites were measured from the same place in the same hemisphere sequentially six times in a 20-min period, the "within-run" CVs ranged from 4.4% to 17.2% for metabolite areas and from 9.7% to 17.0% for metabolite area ratios. The between-days CVs for the subjects ranged from 7.7% to 25.8% (metabolite areas) and from 10.1% to 22.6% (metabolite area ratios). The variability is due to a combination of random noise, subject motion, baseline artefacts in the spectra, and uncertainties in repositioning the VOIs. It is likely to represent the best reproducibility possible with 8-ml VOIs in cooperative, healthy volunteers carefully positioned on each occasion in a standard clinical scanner. Changes in metabolite levels in individuals must therefore be of the order of 20-40% before we can be reasonably confident of measuring them. Reproducibility in patients, who may be less cooperative, will probably be no better, and this must be taken into account in the interpretation of MRS studies in patients with brain pathology; for example, stroke, head injury, and tumours.

Adult↗