Capecitabine plus rofecoxib show no activity in patients with metastatic neuroendocrine tumours.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
S Chin
Publications and source records attributed to S Chin.
Micellar solubilisation of cholesterol is essential for absorption in humans.
BACKGROUND AND AIMS: Intralumenal bile acid (BA) concentrations have a profound effect on cholesterol absorption. We performed studies to assess the effects of markedly reduced lumenal BA on cholesterol absorption in children with inborn errors in BA synthesis and the role of micellar solubilisation of cholesterol on its absorption in an animal model using human intestinal contents. METHODS: We studied five subjects: two with 3beta hydroxy-C27 steroid dehydrogenase isomerase deficiency (3-HSD), two with Delta(4)-3-oxosteroid 5beta reductase deficiency (5beta reductase), and one with 2-methylacyl CoA racemase deficiency (racemase). Subjects were studied on supplemental BA therapy and three weeks after withdrawal of supplements. During each treatment period a liquid meal was consumed. Duodenal samples were collected and analysed, and cholesterol absorption and cholesterol fractional synthetic rates were measured. Human intralumenal contents were infused in a bile diverted rat lymph fistula model to assess micellar versus vesicular absorption of cholesterol. RESULTS: Without BA supplementation, intralumenal BA concentrations were below the critical micellar concentration (CMC) whereas intralumenal BAs increased to above the CMC in all subjects on BA supplementation. Lumenal cholesterol was carried primarily as vesicles in untreated subjects whereas it was carried as both micelles and vesicles in treated subjects. Cholesterol absorption increased approximately 55% in treated compared with untreated subjects (p=0.041), with a simultaneous 70% decrease in synthesis rates (p=0.029). In the rat lymph fistula model, minimal vesicular cholesterol was absorbed whereas vesicular and micellar fatty acid and phospholipid were comparably absorbed. CONCLUSIONS: Increasing micellar cholesterol solubilisation by supplemental BA in subjects with inborn errors of BA synthesis leads to an improvement in cholesterol absorption and reduction in cholesterol synthesis due to improved micellar solubilisation of cholesterol.
3-Hydroxysteroid Dehydrogenases↗
Protective effect of diltiazem on hepatic ischemia-reperfusion injury in rats by improving liver tissue blood flow.
BACKGROUND: Cytosolic calcium ions are known to play an important role in ischemia-reperfusion (IR) injury. However, the protective effect of calcium channel blockers remains controversial in liver IR injury. Moreover, calcium channel blockers improve hepatic IR injury not due to blocking an increase in hepatic calcium concentration. Therefore, we hypothesized that calcium antagonists protected a liver from IR injury by a vasodilatory action rather than by the inhibition of an increase in Ca2+ within parenchymal cells. This study evaluated the effects of diltiazem, a calcium channel blocker, on liver energy metabolism and blood flow after IR injury. METHODS: Twenty-seven rats underwent hepatic ischemia for 30 minutes followed by 60 minutes of reperfusion. The animals were allocated into group C (without drug); group D5 (diltiazem, 5 microg/kg per min); or group D10 (diltiazem, 10 microg/kg per min). Diltiazem was infused before laparotomy and then throughout the experiment. RESULTS: After 60 minutes of reperfusion, liver tissue blood flow and ATP concentrations were significantly higher in group D10 than the other animals (both, P < .05). Changes in ATP values strongly correlated those observed in blood flow (R = 0.80, P < .001). CONCLUSION: Diltiazem improved ATP-generating capacity during reperfusion by improving liver tissue blood flow. An improvement in hepatic tissue perfusion may be a therapeutic strategy for liver IR injury.
Animals↗
Development of a tuberculosis education booklet for Latino immigrant patients.
The incidence and prevalence of tuberculosis are far more common among third world populations immigrating to the United States than among US-born citizens. Immigrants' failure to comply with an anti-tuberculosis treatment can impede completion of care and further confound this public health problem. Barriers to patient--provider communication can negatively influence adherence to a medical regimen. Patients who are unable to comprehend medical advice and do not see it as personally salient are less likely to follow their provider's medical advice. In this paper, the authors focus on efforts to develop a patient education tool targeting Spanish-speaking Latino immigrant patients to facilitate communication with tuberculosis clinicians. A description of the multi-stage developmental processes is presented including conducting a needs assessment, development of visual and written messages, review/critique by tuberculosis experts, field-testing, revisions, and distribution. Formative evaluation and field testing indicates promise for improving communication using this tool.
Emigration and Immigration↗
Dementia with lewy bodies.
In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a man with dementia with Lewy bodies. Dementia with Lewy bodies might be the second most common form of degenerative dementia in the elderly. Progressive cognitive decline, well-formed visual hallucinations, and parkinsonism are core features of this disease. This case was marked by preserved verbal expression despite impairment in memory, visuospatial skills, and attention span. Development of visual symptoms and parkinsonism occurred very early in the course of the disease.
Brain↗
Color and duplex Doppler sonography of hemangiopericytoma.
We report the color Doppler sonographic features in a case of hemangiopericytoma of the thigh in a 52-year-old woman. Color Doppler sonography demonstrated the vascularity of the tumor, and spectral analysis showed waveform changes that suggested the presence of intratumoral arteriovenous shunting. The color Doppler findings correlated well with angiographic findings. Color Doppler sonography can demonstrate intratumoral arteriovenous shunting in hemangiopericytoma and may be used to help avoid profuse bleeding when performing a preoperative biopsy.
Angiography↗
[A frequent fiber-scopic bronchial lavege for the case of bilateral sever pulmonary contusion with flail chest].
A 26-year-old man was injured in the traffic accident. He had complicated chest trauma. He came to our hospital by ambulance immediately after rescued from crashed his automobile. He had severe pulmonary contusion with frail chest, pulmonary laceration, tension hemopneumothorax, and hypovolemic shock, and air embolism of the brain. He was managed with fiber-optic bronchoscopy under mechanical ventilation and chest drainage. Frequent broncho-scopic bronchial lavage of respiratory tract with thrombin and adrenaline solution was helpful to prevent anoxia due to complicated chest injury. He developed acute bacterial empyema and multiple organ failure due to septic shock during intensive care for trauma. However, he underwent surgical treatment for empyema and fully returned to his work after 6 months after his critical accident.
Accidents, Traffic↗
Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal neuronavigation.
We present a system involving a computer-instrumented fluoroscope for the purpose of 3D navigation and guidance using pre-operative diagnostic scans as a reference. The goal of the project is to devise a computer-assisted tool that will improve the accuracy, reduce risk, minimize the invasiveness, and shorten the time it takes to perform a variety of neurosurgical and orthopedic procedures of the spine. For this purpose we propose an apparatus that will track surgical tools and localize them with respect to the patient's 3D anatomy and pre-operative 3D diagnostic scans using intraoperative fluoroscopy for in situ registration and embedded fiducials. Preliminary studies have found a fiducial registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48 mm. The resulting system leverages equipment already commonly available in the operating room (OR), providing an important new functionality that is free of many current limitations, while keeping costs contained.
Artificial Intelligence↗
Quantification of the gravity-dependent change in the C-arm image center for image compensation in fluoroscopic spinal neuronavigation.
In the quest to develop a viable, frameless spinal navigation system, many researchers are utilizing the C-arm fluoroscope. However, there is a significant problem with the C-arm that must be quantified: the gravity-dependent sag effect resulting from the geometry of the C-arm and aggravated by the inequity of weight at each end of the C-arm. This study quantified the C-arm sag effect, giving researchers the protocol and data needed to develop a program that accounts for this distortion. The development of spinal navigation algorithms that account for the C-arm sag effect should produce a more accurate spinal navigation system.
Artifacts↗
Cytotoxic T cells specifically induce Fas on target cells, thereby facilitating exocytosis-independent induction of apoptosis.
Cytotoxic T (Tc) cells deficient in perforin lyse Fas-negative targets after lengthy incubation periods. This process is independent of granzymes, and killing occurs via the Fas pathway for the following reasons. Interaction of perforin-deficient Tc cells with Fas-negative targets leads to an up-regulation of Fas that is dependent on Ag recognition, de novo synthesis, and transport of proteins to the target cell surface. Treatment of effectors with brefeldin A, but not with the exocytosis inhibitor concanamycin, inhibited this process. Lysis of targets is inhibited by anti-Fas Abs, soluble mouse Fas-Fc, and the caspase-cascade inhibitor, crm-A. Targets from Fas-mutant lpr mice are refractory to lysis, and Tc cells from mice deficient in Fas- and perforin-mediated lysis do not lyse Fas-negative targets. The possible relevance of this exocytosis-independent cytolytic process in the regulation of T cell activity and control of pathogens is discussed.
Animals↗
Levodopa-induced dyskinesias in autopsy-proven cortical-basal ganglionic degeneration.
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Aged↗
Recessively inherited spastic paraplegia associated with ataxia, congenital cataracts, thin corpus callosum and axonal neuropathy.
We investigated a consanguineous Japanese family with a complicated form of familial spastic paraplegia (FSP). Three siblings were affected, probably by autosomal recessive inheritance. All showed ataxia, subnormal mentality, congenital cataracts, and slight cerebellar atrophy on CT scans. Spastic paraplegia was predominant in 2 siblings, while ataxia was more marked in the other. Slight but definite atrophy of the corpus callosum and axonal neuropathy were demonstrated in 1 sibling who underwent detailed investigation. Review of similar cases reported in the literature indicates that this recessively inherited disorder probably represents a homogeneous group within the heterogeneous cluster of complicated FSP.
Adult↗
Efficacy of a 1-week pantoprazole triple therapy in eradicating Helicobacter pylori in Asian patients.
BACKGROUND: The aim of the present paper was to determine the efficacy and tolerability of a 1-week treatment regimen consisting of pantoprazole and two antibiotics: clarithromycin and amoxycillin, in the eradication of Helicobacter pylori. METHODS: The patients selected had unequivocal evidence of H. pylori infection based on urease test, culture and histology on antral and corpus biopsies obtained at endoscopy. Patients received pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day and amoxycillin 1 g twice a day for 1 week and were assessed for successful eradication at least 4 weeks after completion of therapy by repeat gastroscopy and gastric biopsies. Eradication was defined as absence of bacteria in both antral and corpus biopsies tested by culture, histology and urease test. RESULTS: One hundred and six patients were recruited for the study. The mean age was 48.0 years (range: 23-74 years). Four patients defaulted follow up and five patients were not compliant (taking less than 85%) with medications. Eradication rates on per-protocol analysis were: 88/97 (90.7%; 95% CI: 83.1-95.7); and on intention-to-treat analysis they were: 88/106 (83.0%; 95% CI: 75.9-90.2). Side-effects were in general mild and tolerable: 57 of 106 (53.7%) patients complained of a bitter taste; 15 (14.1%) complained of giddiness; 10 (9.4%) complained of increased abdominal pain; 11 (11.5%) complained of lethargy and 16 (15.1%) complained of loose motions. Pre-treatment metronidazole resistance was encountered in 57/74 strains (77.0%). Clarithromycin resistance was not encountered in any of the strains. CONCLUSIONS: The pantoprazole 1-week triple therapy with amoxycillin and clarithromycin is effective in H. pylori eradication. The treatment was well tolerated by patients. Metronidazole resistance was reported in a high percentage of strains isolated from patients. Clarithromycin resistance was, however, not detected in any of the strains.
2-Pyridinylmethylsulfinylbenzimidazoles↗
[Oculomotor deficits produced by unilateral chemical deactivation of the cerebellar flocculus in alert cats].
We have reported earlier that in alert cats the cerebellar flocculus contains many Purkinje cells that respond to pitch (vertical) rotation and that the majority of them receive excitation from the contralateral posterior canal. To understand the role of the flocculus in oculomotor function, I first examined the simple-spike activity of floccular Purkinje cells responding to sinusoidal pitch rotation and vertical optokinetic stimuli, and then injected the GABA agonist muscimol into the flocculus to examine oculomotor deficits. The great majority of Purkinje cells responded to upward pitch rotation and downward optokinetic stimuli, with their response phases near the resultant eye velocity. Following muscimol injection into the up-pitch areas (1 microgram), the down vestibulo-ocular reflex (VOR) induced by up-pitch was depressed at low (not high) stimulus frequencies. Down optokinetic responses were virtually abolished. The cats failed to maintain downward gaze position, and postsaccadic exponential centripetal drift appeared with the mean time constant of 0.7 s. Ocular torsion also appeared on the eye ipsilateral to the injection side in 2 of 3 cats examined. These results indicate the involvement of the flocculus in down and torsional slow eye movements.
Animals↗
Improving the delivery of care and reducing healthcare costs with the digitization of information.
In the coming years, the digitization of information and the Internet will be extremely powerful in reducing healthcare costs while assisting providers in the delivery of care. One example of healthcare inefficiency that can be managed through information digitization is the process of prescription writing. Due to the handwritten and verbal communication surrounding prescription writing, as well as the multiple tiers of authorizations, the prescription drug process causes extensive financial waste as well as medical errors, lost time, and even fatal accidents. Electronic prescription management systems are being designed to address these inefficiencies. By utilizing new electronic prescription systems, physicians not only prescribe more accurately, but also improve formulary compliance thereby reducing pharmacy utilization. These systems expand patient care by presenting proactive alternatives at the point of prescription while reducing costs and providing additional benefits for consumers and healthcare providers.
Clinical Pharmacy Information Systems↗
Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes.
Analysis of perforin-deficient mice has identified the cytolytic pathway and perforin as the preeminent effector molecule in T cell-mediated control of virus infections. In this paper, we show that mice lacking both granzyme A (gzmA) and granzyme B (gzmB), which are, beside perforin, key constituents of cytolytic vesicles, are as incapable as are perforin-deficient mice of controlling primary infections by the natural mouse pathogen ectromelia, a poxvirus. Death of gzmAxgzmB double knockout mice occurred in a dose-dependent manner, despite the expression of functionally active perforin and the absence of an intrinsic defect to generate splenic cytolytic T cells. These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens.
Animals↗
A subtype of sporadic prion disease mimicking fatal familial insomnia.
OBJECTIVE: To establish a variant of sporadic prion disease as the sporadic form of fatal familial insomnia (FFI). BACKGROUND: FFI is a recently described prion disease characterized clinically by severe sleep impairment, dysautonomia, and motor signs, and pathologically by atrophy of thalamic nuclei, especially the medial dorsal and anterior ventral, and of the inferior olive. FFI is linked to the D178N mutation coupled with the methionine codon at position 129 in the prion protein gene (PRNP). It is also identified by the properties of the abnormal prion protein (PrP(Sc)), which has the relative molecular mass of 19 kDa, corresponding to the so-called type 2, and a marked underrepresentation of the unglycosylated form relative to the diglycosylated and monoglycosylated forms. METHODS: Clinical, pathologic, PrP(Sc), and PRNP data from 5 subjects with a sporadic prion disease phenotypically similar to FFI were collected and analyzed. RESULTS: All 5 subjects had a disease clinically similar and histopathologically virtually identical to FFI. PrP(Sc) type 2 was present in all subjects in amount and distribution similar to those of FFI. However, the PrP(Sc) did not show the striking underrepresentation of the unglycosylated isoform of the protein that is characteristic of FFI. Moreover, none of the subjects had the D178N PRNP mutation but all were homozygous for methionine at codon 129. CONCLUSION: This condition is likely to represent the sporadic form of FFI and the term "sporadic fatal insomnia" is proposed.
Adult↗
Delay in gynecologic surgical treatment: a comparison of patients in managed care and fee-for-service plans.
OBJECTIVE: To determine whether membership in a managed care organization is associated with a delay in receiving definitive surgical treatment for benign gynecologic or gynecologic oncologic diseases. METHODS: Four hundred patients who had definitive surgery between 1994 and 1997 were divided into those with benign gynecologic (n = 207) and gynecologic oncologic diagnoses (n = 193). Each group was subdivided into managed care patients and fee-for-service patients. Subgroups were analyzed for delay in surgical treatment, emergency room visits, length of stay, age, clinic visits, prior evaluation, prior treatment, second opinions, operating room time, estimated blood loss, and surgical complications. RESULTS: There were 122 managed care and 85 fee-for-service patients with benign gynecologic diagnoses. The time from initial presentation to the date of definitive surgery was significantly longer for the managed care patients (133.7 +/- 21 days compared with 84.9 +/- 12.8 days, P = .03). Of the 193 patients with gynecologic cancer 96 were in the managed care group and 97 were under fee-for-service arrangements. There was no significant difference in the time from initial presentation to the date of definitive surgery between these two groups (35.7 +/- 7.4 days compared with 20.5 +/- 2.5 days, P = .29). There were no significant differences between groups in emergency room or clinic visits, prior evaluations or treatments, or surgical complications when stratified by diagnosis. The mean age of managed care patients was significantly lower than that of fee-for-service patients for gynecologic diagnoses (46.4 +/- 9.7 years compared with 56.5 +/- 14.9 years, P < .001), and gynecologic oncologic diagnoses (47.5 +/- 13.2 years compared with 60.9 +/- 15.8 years, P < .001). CONCLUSION: Membership in a managed care organization is associated with a delay in receiving definitive surgical care for benign gynecologic, but not gynecologic oncologic, diseases.
Arizona↗