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41.
42.
Tom Rossenbacker MD Sheila J. Carroll MD Huajun Liu MD Cuno Kuipri Thomy J.L. de Ravel FCP Koen Devriendt MD PhD Peter Carmeliet MD PhD Robert S. Kass PhD Hein Heidbüchel MD PhD 《Heart rhythm》2004,1(5):611-615
OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations. METHODS: Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures. RESULTS: A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making. 相似文献
43.
RTI-121 and RTI-122 are 3 beta-substituted phenyltropane analogs of cocaine that have high, selective binding affinity for dopamine transporters. [123I]RTI-121 and [123I]RTI-122 bind to dopamine transporters in vivo after intravenous administration and permit imaging of the transporters. 相似文献
44.
Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment. 相似文献
45.
Miguel JA Láinez 《Neuropsychiatric Disease and Treatment》2006,2(3):247-259
Migraine is a common, disabling disorder associated with considerable personal and societal burden. Current guidelines recommend triptans for the acute treatment of migraine unlikely to respond to less effective therapies. Rizatriptan is a second-generation triptan available in tablet or orally disintegrating tablet (wafer) formulations that offers several advantages over other members of its class. Rizatriptan is rapidly absorbed from the gastrointestinal tract and achieves maximum plasma concentrations more quickly than other triptans, providing rapid pain relief. Clinical trials have shown that rizatriptan is at least as effective or superior to other oral migraine-specific agents in the acute treatment of migraine, and has more consistent long-term efficacy across multiple migraine attacks. Rizatriptan has a favorable tolerability profile, and patients have reported greater satisfaction and a preference for rizatriptan over other migraine-specific agents. Improvements in quality of life reported with rizatriptan are consistent with its favorable efficacy and tolerability profiles. Notably, multi-attribute decision models that combine clinical data with patient- and physician-reported treatment preferences have identified rizatriptan as one of three triptans closest to a hypothetical “ideal”. The efficacy and tolerability of rizatriptan for the acute treatment of migraine have thus been well established. 相似文献
46.
47.
48.
L. C. Walker C. A. Parker W. J. Lipinski M. J. Callahan R. T. Carroll S. E. Gandy J. D. Smith M. Jucker C. L. Bisgaier 《The American journal of pathology》1997,151(5):1371-1377
To assess the influence of age and diet on cerebral pathology in mice lacking apolipoprotein E (apoE), four male apoE knockout mice (epsilon -/-), and five male wild-type (epsilon +/+) littermate controls were placed on a high-fat/high-cholesterol diet for 7 weeks beginning at 17 months of age. All four aged knockout mice developed xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were confined mainly to the choroid plexus and ventral fornix in the roof of the third ventricle, occasionally extending subpially along the choroidal fissure and into the adjacent parenchyma. More advanced xanthomas disrupted adjoining neural tissue in the fornix, hippocampus, and dorsal diencephalon; in one case, over 60% of one telencephalic hemisphere, including nearly the entire neocortex, was obliterated by the lesion. No xanthomas were observed in aged wild-type controls fed the high-fat/high-cholesterol diet. Brains from 42 additional animals, fed only conventional chow, were examined; 3 of 15 aged (15- to 23-month-old) apoE knockout mice developed small choroidal xanthomas. In contrast, no lesions were observed in five young (2- to 4-month-old) apoE knockout mice or in any wild-type controls between the ages of 2 and 23 months. Our findings indicate that disorders of lipid metabolism can induce significant pathological changes in the central nervous system of aged apoE knockout mice, particularly those on a high-fat/high-cholesterol diet. It may be fruitful to seek potential interactions between genetic factors and diet in modulating the risk of Alzheimer's disease and other neurodegenerative disorders in aged humans. 相似文献
49.
We present a comprehensive, meta‐analytic review and critical evaluation of outcome research pertaining to the effectiveness of premarital prevention programs. Results revealed that the mean effect size for premarital programs was .80, which means that the average person who participated in a premarital prevention program was significantly better off afterwards than 79% of people who did not participate. Stated differently, the average participant in a premarital program tends to experience about a 30% increase in measures of outcome success. Our findings suggest that premarital prevention programs are generally effective in producing immediate and short‐term gains in interpersonal skills and overall relationship quality and that these improvements are significantly better than nonintervention couples in these areas. However, because of a lack of extended follow‐up research, conclusions about long‐term effectiveness remain elusive. We propose implications for future research, education, and policy. 相似文献
50.
Chesser A; Carroll M; Lightowler C; Macdougall I; Britton K; Baker L 《Nephrology, dialysis, transplantation》1997,12(1):97-100
Background. Technetium-99m methoxy isobutyl isonitrile
(Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as
thallium-technetium subtraction imaging in the preoperative localization of
hyperplastic parathyroid glands in patients with renal failure. Reports
have suggested that 50% of glands can be identified correctly by this
method. The aim of this study was to improve on previous results and
demonstrate that Tc-99m MIBI imaging has an important place in the
preoperative work-up of these patients. Methods.
Eighteen patients on renal replacement therapy were studied. All had
tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to
parathyroidectomy. A refined reporting method was employed. The imaging
results were compared to the subsequent surgical and histological findings.
Results. In the 12 patients in whom serum parathyroid
hormone levels fell postoperatively to within or below the normal range, 38
of 46 glands (82.6%) were correctly identified and located in the correct
quadrant of the thyroid gland. There were two false positive results where
the imaging predicted glands not subsequently found by the surgeon. In the
patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI
imaging was able to locate accurately the site of the residual parathyroid
tissue. Conclusion. Tc-99m MIBI imaging is able to
identify more than 80% of hyperplastic parathyroid glands in renal failure
patients if this reporting process is used, and locate them in the correct
quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value
when re-exploration of the neck is required for post-parathyroidectomy
hyperparathyroidism. These results represent a significant improvement on
the sensitivity of this imaging technique when compared to previous
published data. 相似文献