Ryanodine receptor permeation and gating: glowing cinders that underlie the Ca2+ spark.
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Biomedical subjects
Publications and source records attributed to A Escobar.
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Neurocysticercosis (NC) remains a major public health problem in developing and some developed countries. Currently, the best procedures for diagnosing NC are neuroimaging studies. Immunoserologic assays, such as enzyme-linked immunoelectrotransfer blot assay (EITB) or enzyme-linked immunosorbent assay (ELISA), detect antibodies against Taenia solium, or cysticercus. Consequently, they are useful in identifying a population at risk of contact with the parasite but do not necessarily indicate a systemic active infection. Most seropositive individuals are asymptomatic. No data from prospective studies concern the proportion of these individuals that will develop seizures or other neurologic symptoms. There is a discrepancy between the results of serologic assays and neuroimaging studies: >50% of those individuals with NC diagnosed by computed tomography (CT) scan test EITB negative. Pathophysiologic classification of NC into active, transitional, and inactive forms permits a good correlation between clinical manifestations and neuroimaging procedures and facilitates medical and surgical management and research. The most frequent clinical manifestations of NC are seizures. We assume that NC is the main cause of symptomatic epilepsy in developing countries; however, no case-control or cohort studies demonstrate this association. Most patients with NC with seizures have a good prognosis; nevertheless, further studies analyzing factors related to recurrence of seizures and possibilities of discontinuation of antiepileptic medications (AEDs) are needed. Regarding treatment of NC with antihelminthic drugs, no controlled clinical trials exist that establish specific indications, definitive doses, and duration of treatment. The most effective approach to taeniasis/cysticercosis infection is prevention. This should be a primary public health focus for developing countries. We critically review the available information regarding the epidemiology and diagnosis of human cysticercosis, the physiopathology and imaging correlation of the parasite in the central nervous system (CNS) of the host, the relation between seizures or epilepsy and NC, and the issues surrounding the treatment and prognosis of NC, including the use of antihelminthic therapy.
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BACKGROUND: Barbiturates, benzodiazepines, and synthetic steroids having anesthetic properties, by enhancing the inhibitory GABAergic neurotransmission to the neuronal circuits of cerebral structures vulnerable to ischemia, reduce the damage induced by this condition. Some endogenous steroids resulting from progesterone (P4) biotransformation in the brain exert GABAergic effects, thus inhibiting neuronal excitability. Hence, P4 administration both before and after an experimentally induced ischemic episode may prevent or decrease the ischemic cerebral damage. METHODS: Ovariectomized adult cats were treated s.c. with either P4 (10 mg/kg/day) or corn oil during 7 days before and 7 days after being subjected to a period of acute global cerebral ischemia by 15 min of cardiorespiratory arrest followed by 4 min of reanimation. After 14 days of survival, animals were sacrificed and the brains perfused in situ and formalin-fixed for histological examination. RESULTS: Acute global cerebral ischemia resulted in a severe loss of neurons (54-85%), mainly in CA1 and CA2 subfields of oil-treated cats. Progesterone significantly reduced the neuronal loss in those areas (21-49%). CONCLUSIONS: Overall results suggest that progesterone exerts protective effects against the neuronal cerebral damage induced by acute global cerebral ischemia.
OBJECTIVES: We assessed the safety and efficacy of stent placement in patients with poorly controlled hypertension and renal artery stenoses, which are difficult to treat with balloon angioplasty alone. BACKGROUND: Preliminary experience with stent placement suggests improved results over balloon angioplasty alone in patients with atherosclerotic renal artery stenosis. METHODS: Balloon-expandable stents were placed in 100 consecutive patients (133 renal arteries) with hypertension and renal artery stenosis. Sixty-seven of the patients had unilateral renal artery stenosis treated and 33 had bilateral renal artery stenoses treated with stents placed in both renal arteries. RESULTS: Angiographic success, as determined by quantitative angiography, was obtained in 132 (99%) of 133 lesions. Early clinical success was achieved in 76% of the patients. Six months after stent placement, the systolic blood pressure was reduced from 173 +/- 25 to 147 +/- 23 mm Hg (p < 0.001); the diastolic pressure from 88 +/- 17 to 76 +/- 12 mm Hg (p < 0.001); and the mean number of antihypertensive medications per patient from 2.6 +/- 1 to 2.0 +/- 0.9 (p < 0.001). Angiographic follow-up at a mean of 8.7 +/- 5.0 months in 67 patients revealed restenosis (>50% diameter narrowing) in 15 (19%) of 80 stented vessels. CONCLUSIONS: Renal artery stenting is an effective treatment for renovascular hypertension, with a low angiographic restenosis rate. Stent placement appears to be a very attractive therapy in patients with lesions difficult to treat with balloon angioplasty such as renal aorto-ostial lesions and restenotic lesions, as well as after a suboptimal balloon angioplasty result.
BACKGROUND: Patients with diabetes mellitus have a higher prevalence of atherosclerotic heart disease and a higher incidence of myocardial infarction than the general population. Diabetic patients also have several hematologic, rheologic, and metabolic abnormalities not present in their nondiabetic counterparts that may predispose them to atherosclerotic plaque rupture and intraluminal thrombosis and consequently may lead to the formation of morphologically complex plaques and the development of acute coronary syndromes. METHODS AND RESULTS: Percutaneous coronary angioscopy was performed in 55 consecutive patients with unstable angina. We observed plaque color, texture, and the incidence of intracoronary thrombus associated with the culprit lesions of these patients. The population consisted of 17 (31%) diabetic and 38 (69%) nondiabetic patients. The presence of coronary risk factors was not significantly different between the two populations. Ulcerated plaque was found in 16 of 17 (94%) diabetic patients versus 23 of 38 (60%) nondiabetic patients (P = .01). Intracoronary thrombi were seen in 16 of 17 (94%) diabetic patients versus 21 of 38 (55%) nondiabetic patients (P = .004). CONCLUSIONS: The results of the angioscopic examination show that diabetic patients with unstable angina have a higher incidence of plaque ulceration and intracoronary thrombus formation than nondiabetic patients. This increased frequency of complex lesion morphology is consistent with the disproportionately higher risk for development of acute coronary syndromes in these patients.
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OBJECTIVES: This study used angioscopy to determine the specific cause of vessel occlusion after percutaneous transluminal coronary angioplasty and compared the angiographic and angioscopic lesion morphologies in this setting. BACKGROUND: Occlusion of a dilated coronary artery is the major cause of morbidity and mortality after coronary angioplasty. Attempts to reopen occluded vessels are either empirically guided or directed by angiography, which has inherent limitations. Angioscopy, the in vivo direct visualization of the endovascular surface, is potentially a more accurate means of identifying the cause of vessel occlusion after angioplasty. METHODS: Percutaneous coronary angioscopy was performed in 17 patients (17 vessels) after angiographic confirmation of postangioplasty vessel occlusion. RESULTS: Angioscopy demonstrated the primary cause of the postangioplasty occlusion to be dissection in 14 patients (82%) and intracoronary thrombi in 3 (18%). Compared with angioscopy, angiography was significantly less accurate in identifying the specific cause of the occlusion and correctly identified the cause of vessel occlusion in only 5 (29%) of 17 patients (p < 0.001), including 4 (29%) of 14 deep dissections and 1 (33%) of 3 occlusive thrombi. CONCLUSIONS: Angioscopy specifically identified the cause of occlusion in every patient, with coronary dissection the predominant cause of abrupt occlusion after coronary angioplasty. However, angiography was unable to identify a specific cause for vessel occlusion in the majority of our patients. Angioscopy may therefore prove useful in selecting specific treatment strategies for patients with abrupt occlusion after angioplasty, such as stent placement, atherectomy, repeat dilation or thrombolysis.
The precise guidelines recommended by the American Heart Association for blood pressure measurement are commonly overlooked by health-care workers, who generally take blood pressure in an arbitrary way. To validate this observation we designed a descriptive and observational study to be carried out in a major hospital. One hundred and seventy-two health-care workers divided into four groups (63 general practitioners, 25 clinical and 25 surgical specialists, and 59 nurses) were evaluated in a two-part test. In the first part (practical), the examinee had to follow all the steps recommended by the American Heart Association to get a passing score. In the second part (theoretical, which came second to avoid influencing the practical), the examinee had to answer correctly 7 of 10 questions based on the American Heart Association's guidelines to obtain a passing score. The highest accepted variation in systolic and diastolic pressures between examinee and observer was +/- 4 mm Hg. None of the examinees followed the American Heart Association's recommendations. Sixty-three percent of systolic and 53% of diastolic readings were out of range. Surgical specialists obtained the best practical results (48% systolic and 64% diastolic within range), and nurses obtained the lowest values (29% and 39%, respectively; P = .03 versus surgical specialists). These two groups showed deficiencies in the theoretical test (nurses, 10% correct answers and surgical specialists, 16%). Clinical specialists obtained the best results on the theoretical test (60% correct; P < .05 versus the other groups) but were deficient in the practical test (32% systolic and 60% diastolic within range).(ABSTRACT TRUNCATED AT 250 WORDS)
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The genesis of cardiac allograft vasculopathy has been linked to nonimmunologic endothelial injury. Studies evaluating the role of nonimmunologic risk factors have thus far been limited to angiographic assessment. Intravascular ultrasound can detect cardiac allograft vasculopathy before it becomes angiographically evident. To assess the influence of nonimmunologic risk factors in the development of cardiac allograft vasculopathy, we studied 101 consecutive cardiac transplant recipients who underwent intracoronary ultrasound imaging during routine, annual coronary angiography. Based on the severity of intimal thickening, patients were divided into 2 groups: group 1 = minimal, mild, or moderate intimal thickness; and group 2 = severe intimal thickness. Cardiac transplant recipients with severe intimal thickness had higher levels of total cholesterol (267 +/- 70 vs 227 +/- 41 mg/dl, p = 0.0008), low-density lipoprotein cholesterol (187 +/- 47 vs 139 +/- 31 mg/dl, p = 0.0001), and triglycerides (237 +/- 75 vs 182 +/- 88 mg/dl, p = 0.0004), a higher percentage of weight gain (12 +/- 4% vs 8 +/- 5%, p = 0.0001), a larger body mass index (30 +/- 4 vs 25 +/- 3, p = 0.0001), and older donor age (27 +/- 5 vs 23 +/- 7 years, p = 0.005) than recipients with mild or moderate intimal thickness. Multiple regression analysis established that total cholesterol, low-density lipoprotein cholesterol, triglyceride levels, obesity indexes, donor age, and years following cardiac transplantation (p < 0.01) were independent predictors of the severity of intimal thickening, and thus the severity of cardiac allograft vasculopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
The complicated pathophysiological and immunological changes in the central nervous system of patients with neurocysticercosis produce a variety of signs and symptoms, which complicate the clinical and surgical management of this disease. A complete and objective classification is needed, to improve the medical approach as a whole. We studied 336 patients, in whom we classified neurocysticerosis according to criteria of viability and location of the parasite in the CNS: active form (37.2%) when the cysticercus is alive, transitional form (32.8%) when it is in the degenerative phase, and inactive form (30%) when the parasite is dead. This classification establishes the correlation between the different forms of neurocysticerosis and its clinical manifestations, and can be used for planning therapeutic strategies.
BACKGROUND: Cardiac allograft vasculopathy remains the leading limitation to long-term survival after cardiac transplantation. While the influence of donor and recipient gender in the pathogenesis of cardiac vasculopathy is still poorly understood, studies have indicated that female allografts may be at higher risk for the development of cardiac allograft vasculopathy. The purpose of this study was to characterize the influence of donor and recipient gender on the early genesis of cardiac allograft vasculopathy by using intravascular ultrasound. METHODS AND RESULTS: Thirty-six consecutive cardiac transplant recipients were divided into three groups on the basis of donor and recipient gender as follows: group 1, female donor and male recipient (n = 8); group 2, male donor and female recipient (n = 7); and group 3, male donor and male recipient (n = 21). The three groups were similar with regard to donor and recipient age, weight, body surface area, serum lipids, left ventricular function, histocompatibility, cellular and vascular rejection, and cytomegalovirus infection. To precisely quantitate the extent of cardiac allograft vasculopathy, intravascular ultrasound was performed in all patients at the time of first annual angiography. Intimal thickening and intimal index were accurately quantitated by intravascular ultrasound. Intimal thickening was significantly greater in group 1 (0.55 +/- 0.15 mm) than in group 2 (0.18 +/- 0.04 mm) or group 3 (0.29 +/- 0.05 mm) (P < .05). In addition, the intimal index was greater in group 1 (0.20 +/- 0.04) than in group 2 (0.07 +/- 0.02) or group 3 (0.15 +/- 0.02) (P < .01, group 1 versus group 2). CONCLUSIONS: Male recipients of female allografts have a higher degree of vascular intimal hyperplasia detected by intravascular ultrasound at 1 year after heart transplantation. These findings indicate that donor and recipient gender influences the early genesis of cardiac allograft vasculopathy.
Angioplasty of coronary saphenous vein grafts has been associated with less favorable results than in native coronary arteries owing to a higher acute complication rate and an increased incidence of restenosis. We placed 16 nonarticulated balloon expandable stainless steel "biliary" stents at the sites of 13 stenotic or occluded aortocoronary saphenous vein graft lesions in 11 patients. All of the lesions were stented successfully. There were no instances of stent thrombosis or stent embolism. The percent diameter stenosis was reduced from 85.5 +/- 14.1% to 3.5 +/- 4.4% (p < .001), and the minimal lumen diameter of the lesion increased from 0.7 +/- 0.7 mm at baseline to 3.7 +/- 0.2 mm (p < .001) after stent placement. We conclude that this noncoronary stent appears to be safe and effective for treating saphenous vein coronary bypass grafts. The high procedural success rate and excellent angiographic results are very encouraging, while the restenosis rates remain to be determined.
A strategy of using a single, conservatively sized percutaneous transluminal rotational ablation device with or without adjunctive balloon angioplasty was employed in 18 vessels in 17 patients selected because of unfavorable lesion morphology for balloon angioplasty alone. Fifteen patients had lower extremity occlusions and/or heavily calcified lesions and two patients had ostial renal artery stenoses. We were able to achieve a 94% (17/18 lesions) technical success rate, and a 94% (16/17 patients) clinical success rate. In the patients with lower extremity lesions, the baseline ankle-brachial blood pressure index increased from 0.55 +/- 0.15 to 0.90 +/- 0.19 (p < .001) 1 day after the procedure. Follow-up at 6.8 +/- 2.8 months revealed clinical evidence of restenosis in only one patient. We conclude that a cost-effective strategy of treating unfavorable lesions with a single Rotablator burr and adjunctive balloon angioplasty is safe and effective.
A pulse oximeter sensor is used to monitor changes in arterial hemoglobin oxygen saturation (SpO2) in anesthetized pediatric patients. The authors compared the kinetics of desaturation and resaturation measured by sensors placed over central (tongue, cheek) and peripheral (finger, toe) vascular beds in children with congenital heart disease. Desaturation time was defined as the time which elapsed between the onset of apnea and a 4% decrease in SpO2 from baseline. The desaturation times averaged 24 +/- 12 s, 56 +/- 34 s, and 58 +/- 28 s for the cheek, finger, and toe, respectively (n = 40; P < 0.0001 for cheek versus finger or toe). Resaturation time was defined as the interval between the resumption of ventilation and a 4% increase in SpO2 above the nadir. Resaturation times averaged 12 +/- 8 s for the cheek, 40 +/- 36 s for the finger, and 47 +/- 25 s for the toe (n = 40; P < 0.0001 for cheek versus finger or toe). A comparison of the kinetics at two central sensor sites, cheek and tongue, respectively, revealed no significant differences in desaturation times (20 +/- 10 s vs 21 +/- 9 s) or resaturation times (10 +/- 6 s vs 7 +/- 3 s) (n = 13). The authors conclude that both desaturation and resaturation are detected earlier by centrally placed sensors.
Sealed right-side-out reticulocyte ghosts transported and accumulated iron offered as 59Fe(2+)-ascorbate (Km = 1.1 microM). The uptake of iron by ghosts presented the characteristics of a transporter-mediated process: it responded to osmotic challenge, the rate of transport increased when iron was present in the opposing side, and the transport rate showed the temperature dependence typical of membrane-mediated processes. The transport of iron was dependent on an associated influx of Cl- in order to keep electroneutrality. Other transition metals, such as Cu2+, Zn2+, and Co2+, inhibited the transport of Fe2+. The overall characteristics of the system make reticulocyte sealed ghosts a very useful model in determining the basic mechanisms of membrane iron transport.