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91.
W. Dickey F. Stewart J. Nelson G. McBreen S. A. McMillan K. G. Porter 《Clinical genetics》1996,49(2):106-108
Coeliac disease is an important cause of malabsorption, particularly of folic acid, in adults. We investigated the possibility that it might be a maternal risk factor for neural tube defect (NTD)-associated pregnancy by screening affected mothers using serum endomysial antibody (EmA) which has high sensitivity and specificity for coeliac disease. One (1.6%) of 60 patients was EmA positive and had a diagnosis of coeliac disease confirmed by the finding of villous atrophy on jejunal biopsy. In conclusion, the majority of NTD-associated pregnancies are not associated with maternal coeliac disease and our study is additional evidence that abnormalities of folic acid metabolism rather than absorption are the most important risk factors for NTD. Further studies are needed to determine whether the coeliac disease prevalence among women with NTD-affected pregnancy is higher than that of the general population. 相似文献
92.
Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage An alloimmune abnormality is believed to be the cause of recurrent miscarriage in couples in whom no other cause can be identified. Because of its immunosuppressive properties, intravenous immunoglobulin (IVIG) is used as a treatment for this disorder. The purpose of this study was to determine whether IVIG improves the chance of successful pregnancy in women with recurrent miscarriage by using individual patient data from efficacy trials. Detailed information on each patient enrolled in these trials was obtained to evaluate the efficacy of IVIG and investigate the effect of clinical variability on pregnancy outcome. Data from 125 patients in the IVIG group and 115 patients in the placebo group were available for analysis. Although the number of previous miscarriages and female age were both negative prognostic factors for successful outcome, there was no significant improvement in successful pregnancy or live birth rate with IVIG. Subgroup analyses indicated that timing of IVIG administration may be important. The results of the present study highlight the importance of stratification for known confounders, so that the role of IVIG can be evaluated in more detail. The collective evidence thus far indicates that IVIG does not have a therapeutic effect that is clinically meaningful. 相似文献
93.
Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor 总被引:3,自引:0,他引:3
Zili An Xiaoen Wang Neville Willmott Surinder K. Chander Simon Tickle Andrew J. P. Docherty Andrew Mountain Andrew T. Millican Richard Morphy John R. Porter R. Ola Epemolu Tetsuro Kubota A. R. Moossa Robert M. Hoffman 《Clinical & experimental metastasis》1997,15(2):184-195
In this study, we describe the activity of CT1746, an orally-active synthetic MMP inhibitor that has a greater specificity for gelatinase A, gelatinase B and stromelysin than for interstitial collagenase and matrilysin, in a nude mouse model that better mimics the clinical development of human colon cancer. The model is constructed by surgical orthotopic implantation (SOI) of histologically-intact tissue of the metastatic human colon tumor cell line Co-3. Animals were gavaged with CT1746 twice a day at 100 mg/kg for 5 days after the SOI of Co-3 for 43 days. In this model CT1746 significantly prolonged the median survival time of the tumor-bearing animals from 51 to 78 days. Significant efficacy of CT1746 was observed on primary tumor growth (32% reduction in mean tumor area at day 36), total spread and metastasis (6/20 treated animals had no detectable spread and metastasis at autopsy compared to 100% incidence of secondaries in control groups). Efficacy of CT1746 could also be seen on reducing tumor spread and metastasis to individual organ sites such as the abdominal wall, cecum and lymph nodes compared to vehicle and untreated controls. We conclude that chronic administration of a peptidomimetic MMP inhibitor via the oral route is feasible and results in inhibition of solid tumor growth, spread and metastasis with increase in survival in this model of human cancer, thus converting aggressive cancer to a more controlled indolent disease. 相似文献
94.
L S Porter M M Counts M F Borgman P Dieriggi V Miller 《The Journal of nursing education》1985,24(7):270-273
This exploratory study was designed to begin analysis on the "Faculty Work Plan" and its potential for faculty role development in a university setting. The specific goals were: (1) to identify the degree of congruence between faculty work plans and the school goals; and (2) to determine the relationship between faculty work plan/school goal congruence, faculty productivity, potency, and job satisfaction. The sample was composed of 26 respondents, 26 to 50 years old, from a pool of 48 full-time faculty members affiliated with a school of nursing in a university setting. Likert-type rating scores were used to measure Faculty Work Plan-School Goal Congruence (FWP-SG), job satisfaction, productivity, and potency. Data analyses were focused on frequency distribution, group means, and Pearson Correlation Coefficients on selected pairs of variables. Interesting findings were revealed. A strong relationship was found between FWP-SG congruence and faculty productivity (r = .85; p = .000) and potency (r = .84; p = .000). Several recommendations were suggested. 相似文献
95.
The initial results from a diagnostic breast clinic in which clinical examination, x-ray mammography and ultrasound are used to establish a diagnosis during a single patient-visit are described. In 3461 patient-visits, 82 histologically-proven breast cancers were detected. Fifty-two per cent of these cancers were 2 cm or less in diameter and 61% had no axillary lymph-node metastases. Fifteen cancers were impalpable lesions which were detected by mammography alone. The over-all malignant-to-benign biopsy ratio was 1:2.7; for impalpable tumours, this ratio was 1:3.9. The role of such a diagnostic breast clinic is discussed, and attention is drawn to a relatively low attendance of women in the "high-risk" age group of over 50 years of age. 相似文献
96.
Opong-Mensah K Woller TW Obaseki AO Porter WR 《Journal of pharmaceutical and biomedical analysis》1984,2(3-4):381-394
Equations have been developed that relate the concentration (or a parameter directly proportional to concentration, such as optical absorbance) of a weakly ionizable solute in a water-immiscible phase, in equilibrium with an aqueous phase, to the pH of the aqueous phase, the partition coefficient of the unionized solute and the phase volume ratio. These relationships have been used in the design of experimental methods for determining partition coefficients, which require measurement of solute concentration in only one phase. Data obtained in this way permit ready recognition of deviations from assumptions made in the development of the model; these assumptions include insolubility of the ionized solute in the water-immiscible phase and lack of interaction between buffer components and solute. Conditions for optimal liquid—liquid extraction of weakly ionizable solutes are more easily recognized. With these techniques, the negative logarithm of the acid dissociation constant (pK′a) and the logarithm of the octanol—water partition coefficient (log P) have been measured for warfarin (pK′a = 5.15 ± 0.04; log P = 2.82 ± 0.06), strychnine (pK′a = 8.29 ± 0.02; log P = 2.23 ± 0.04), phenol (pK′a = 9.88 ± 0.02; log P = 1.75 ± 0.05), procaine (pK′a = 8.11 ± 0.04; log P = 1.10 ± 0.08), and ephedrine (pK′a = 9.92 ± 0.01; log P = 1.65 ± 0.04) at 21°C. 相似文献
97.
C Camenzuli AN DiMarco KE Isaacs Y Grant J Jackson A Alsafi C Harvey TD Barwick N Tolley FF Palazzo 《Annals of the Royal College of Surgeons of England》2021,103(1):29
IntroductionReoperative parathyroidectomy for persistent and recurrent primary hyperparathyroidism is dependent on radiology. This study aimed to compare outcomes in reoperative parathyroidectomy at a single centre using a combination of traditional and newer imaging studies.Materials and methodsRetrospective case note review of all reoperative parathyroidectomies for persistent and recurrent primary hyperparathyroidism over five years (June 2014 to June 2019; group A). Imaging modalities used and their positive predictive value, complications and cure rates were compared with a published dataset spanning the preceding nine years (group B).ResultsFrom over 2000 parathyroidectomies, 147 were reoperations (101 in group A and 46 in group B). Age and sex ratios were similar (56 vs 62 years; 77% vs 72% female). Ultrasound use remains high and shows better positive predictive value (76% vs 57 %). 99mTc-sestamibi use has declined (79% vs 91%) but the positive predictive value has improved (74% vs 53%). 4DCT use has almost doubled (61% vs 37%) with better positive predictive value (88% vs 75%). 18F-fluorocholine positron emission tomography-computed tomography and ultrasound-guided fine-needle aspiration for parathyroid hormone are novel modalities only available for group A. Both carried a positive predictive value of 100%. Venous sampling with or without angiography use has decreased (35% vs 39%) but maintains a high positive predictive value (86% vs 91%). Cure rates were similar (96% vs 100%). Group A had 5% permanent hypoparathyroidism, 1% permanent vocal cord palsy and 1% haematoma requiring reoperation. No complications for group B.ConclusionOptimal imaging is key to good cure rates in reoperative parathyroidectomy. High-quality, non-interventional imaging techniques have produced a shift in the preoperative algorithm without compromising outcomes. 相似文献
98.
Zafer Tandogdu Justin Collins Greg Shaw Jennifer Rohn Bela Koves Ashwin Sachdeva Ahmed Ghazi Alexander Haese Alex Mottrie Anup Kumar Ananthakrishnan Sivaraman Ashutosh Tewari Benjamin Challacombe Bernardo Rocco Camilo Giedelman Christian Wagner Craig G. Rogers Declan G. Murphy Dmitry Pushkar Gabriel Ogaya-Pinies James Porter Kulthe Ramesh Seetharam Markus Graefen Marcelo A. Orvieto Marcio Covas Moschovas Oscar Schatloff Peter Wiklund Rafael Coelho Rair Valero Theo M. de Reijke Thomas Ahlering Travis Rogers Henk G. van der Poel Vipul Patel Walter Artibani Florian Wagenlehner Kris Maes Koon H. Rha Senthil Nathan Truls Erik Bjerklund Johansen Peter Hawkey John Kelly 《BJU international》2021,127(6):729-741
99.
Jo-Lynn S. Tan Niranjan Sathianathen Marcus Cumberbatch Prokar Dasgupta Alexandre Mottrie Ronney Abaza Koon Ho Rha Thyavihally B. Yuvaraja Dipen J. Parekh Umberto Capitanio Rajesh Ahlawat Sudhir Rawal Nicolò M. Buffi Ananthakrishnan Sivaraman Kris K. Maes Gagan Gautam Francesco Porpiglia Levent Turkeri Mahendra Bhandari Benjamin Challacombe James Roscoe Porter Craig R. Rogers Daniel A. Moon 《BJU international》2021,128(Z3):30-35
100.
William C Stanley Bin Li Douglas W Bonhaus Lowell G Johnson Keiho Lee Seth Porter Keith Walker Greg Martinez Richard M Eglen Roger L Whiting Sharath S Hegde 《British journal of pharmacology》1997,121(8):1803-1809
- Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-β-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and in vivo catecholamine modulatory effects of nepicastat were investigated in the present study.
- Nepicastat produced concentration-dependent inhibition of bovine (IC50=8.5±0.8 nM) and human (IC50=9.0±0.8 nM)dopamine-β-hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2–3 fold less potent than nepicastat. Nepicastat had negligible affinity (>10 μM) for twelve other enzymes and thirteen neurotransmitter receptors.
- Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three consecutive doses of either 3, 10, 30 or 100 mg kg−1, p.o.; 12 h apart) or beagle dogs (0.05, 0.5, 1.5 or 5 mg kg−1, p.o.; b.i.d., for 5 days) produced dose-dependent decreases in noradrenaline content, increases in dopamine content and increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal), left ventricle and cerebral cortex. At the highest dose studied, the decreases in tissue noradrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in dogs) in the artery, left ventricle and cerebral cortex, respectively. When tested at 30 mg kg−1, p.o., in SHRs, nepicastat produced significantly greater changes in noradrenaline and dopamine content, as compared to the R-enantiomer (RS-25560-198), in the mesenteric artery and left ventricle.
- Administration of nepicastat (2 mg kg−1, b.i.d, p.o.) to beagle dogs for 15 days produced significant decreases in plasma concentrations of noradrenaline and increases in plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak reduction (52%) in plasma concentration of noradrenaline and the peak increase (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of dosing, respectively.
- The findings of this study suggest that nepicastat is a potent, selective and orally active inhibitor of dopamine-β-hydroxylase which produces gradual modulation of the sympathetic nervous system by inhibiting the biosynthesis of noradrenaline. This drug may, therefore, be of value in the treatment of cardiovascular disorders associated with over-activation of the sympathetic nervous system, such as congestive heart failure.