Palatal tremor and myorhythmia in Hashimoto's encephalopathy.
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Adult↗
Biomedical subjects
H Carrasco
Publications and source records attributed to H Carrasco.
Tubular hydrogen-bonded networks sustained by water molecules.
The design concept of functional solids relies on controlling the topology of crystal packing through exploitation of weak intermolecular forces. In the context of cyclic aggregates, the ability to anticipate the consequences of ring constituents and their stereochemistries on ring conformation is vitally important since even an apparently slight structural change effected on molecules can dramatically alter the crystal structure. We have found that solid-state structures formed by hydroxy acids with a general structure (+/-)-1 depend on steric interactions. Thus, with the exception of molecules 1b and 1e, compounds (+/-)-1a-(+/-)-1m, which possess bulky and conformationally rigid substituents, aggregate by forming tapes and sheets by alternating (+) and (-) subunits held together through carboxylic acid-to-alcohol hydrogen bonds. Homologue (+/-)-1n, with conformationally flexible substituents which allow conformational deformation, gives, by incorporation of molecules of water, an efficient hexagonal assembly which extends to the third dimension to form tubular H-bonding networks. Each puckered channel can be described as interconnected closely packed hexagons in chairlike conformations. The ethyl groups presented in (+/-)-1n gave the volume required to lock the inner hexagonal wall into a rigid structure. Attempts to obtain cyclic aggregates using small substituents, compounds (+/-)-1o-(+/-)-1q, failed. The observed supramolecular assemblies of the anhydrous compounds can be classified into one-dimensional strands and two-dimensional sheets, while three-dimensional networks are present only in the hydrated molecules (1b, 1e, and 1n). The crystal structure of the anhydrous (+/-)-1n compound confirms the important role played by water molecules in the formation of tubular structures.
Journal Article↗
Detection and significance of inapparent infection in Chagas disease in western Venezuela.
Inapparent infections of Trypanosoma cruzi were detected in symptomless seropositive people living in close proximity, and under the same conditions of risk, to patients with acute Chagas disease. Similar infections were also detected in sera samples of people from 25 villages of western Venezuela where Chagas disease is endemic. Seropositivity in all the 1,251 studied samples was established by use of 3 serological methods (direct agglutination test, indirect immunofluorescence antibody test, and enzyme-linked immunosorbent assay). Each seropositive sample was tested for detection of anti-T. cruzi-specific immunoglobulin (Ig) M and IgG levels and specific T. cruzi infection by molecular methodology (polymerase chain reaction assay). The combined analysis of the serologic (IgM and IgG levels), molecular (specific T. cruzi DNA), and statistical findings demonstrated the existence of a different stage of T. cruzi infection in asymptomatic patients, which is suggested to be recognized as inapparent infection. Its definition, significance, and comparison with typical Chagas disease phases are presented, and its potential epidemiological importance is discussed.
Adolescent↗
A synthetic hydroxy acid that shows tubular-shaped structure in solid-state and ionophoric activity in phospholipid bilayers
[formula: see text] In this contribution, we describe the ability of compound (+/-)-1b and six molecules of water to form in solid-state hexameric aggregates, which self-assemble to give hollow tubular structures. Single-crystal X-ray analysis shows that these tubes are open-ended, with irregular shape and internal van der Waals pore diameter between 6 and 9 A. In addition, transmembrane sodium transport activity was also assessed for (+/-)-1b using dynamic Na(+)-NMR technique.
Journal Article↗
Acute Chagas' disease in western Venezuela: a clinical, seroparasitologic, and epidemiologic study.
A clinical, parasitologic, and serologic study carried out between 1988 and 1996 on 59 acute-phase patients in areas of western Venezuela where Chagas' disease is endemic showed 19 symptomatic patterns or groups of symptoms appearing in combination with different frequencies. The symptomatic pattern with the highest frequency was that showing simultaneously fever, myalgia, headache, and Romaña's sign, which was detected in 20% of the acute-phase patients. Asymptomatic individuals and patients with fever as the only sign of the disease made up 15% and 11.9% of the total acute cases, respectively. Statistical correlation analysis revealed that xenodiagnosis and hemoculture were the most reliable and concordant of the five parasitologic methods used; these two methods also showed the highest proportions in detecting any clinical symptomatic pattern in acute-phase patients. A similar high reliability and concordance was obtained with a direct agglutination test, an indirect immunofluorescent antibody test, and an ELISA as serologic tests, which also showed a higher proportion of positive detection of clinical patterns than parasitologic methods (P < 0.001). It is recommended that individuals coming from endemic areas showing mild and/or severe clinical manifestations should be suspected of being in contact or having been in contact with Trypanosoma cruzi, be referred for parasitologic and serologic evaluations to confirm the presumptive clinical diagnosis of acute Chagas' disease, and start specific treatment. The epidemiologic implications of the present findings are discussed and the use of similar methodology to evaluate other areas where Chagas' disease is endemic is suggested.
Acute Disease↗
Myocardial parasite persistence in chronic chagasic patients.
The persistence of Trypanosoma cruzi tissue forms was detected in the myocardium of seropositive individuals clinically diagnosed as chronic chagasic patients following endomyocardial biopsies (EMBs) processed by immunohistochemical (peroxidase-anti-peroxidase [PAP] staining) and molecular (polymerase chain reaction [PCR]) techniques. An indirect immunofluorescent technique revealed antigenic deposits in the cardiac tissue in 24 (88.9%) of 27 patients. Persistent T. cruzi amastigotes were detected by PAP staining in the myocardium of 22 (84.6%) of 26 patients. This finding was confirmed with a PCR assay specific for T. cruzi in 21 (91.3%) of 23 biopsy specimens from the same patients. Statistical analysis revealed substantial agreement between PCR and PAP techniques (k = 0.68) and the PCR and any serologic test (k = 0.77). The histopathologic study of EMB specimens from these patients revealed necrosis, inflammatory infiltrates, and fibrosis, and made it possible to detect heart abnormalities not detected by electrocardiogram and/or cineventriculogram. These indications of myocarditis were supported by the detection of T. cruzi amastigotes by the PAP technique or its genome by PCR. They suggest that although the number of parasites is low in patients with chronic Chagas' disease, their potential for heart damage may be comparable with those present during the acute phase. The urgent necessity for testing new drugs with long-term effects on T. cruzi is discussed in the context of the present results.
Adult↗
Results of electrophysiologic studies in patients with acute Chagasic myocarditis.
BACKGROUND: As the acute stage of Chagas' myocarditis is rarely detected, little is known about the electrophysiologic characteristics of that stage. HYPOTHESIS: This investigation was undertaken to conduct an electrophysiologic study of the properties of the heart during the acute phase of Chagasic myocarditis. METHODS: We studied eight patients who had positive xenodiagnosis, positive mice culture, and positive complement fixation test for Chagas' disease. RESULTS: Trypanosoma cruzi were identified in all of the patients' stained blood samples. Right ventricular endomyocardial biopsies were obtained, evidencing a distinct infiltrate of lymphocytes that confirmed the diagnosis of acute myocarditis. The cardiac dimensions and the ventricular systolic and diastolic function were preserved in all patients. The electrocardiogram evidenced conduction defects in two patients. The signal-averaged electrocardiogram displayed late potentials in three patients. In the electrophysiologic study, atrial fibrillation or flutter was induced in four patients. When compared with control patients, Chagasic patients were found to have greater values of atrial threshold, A-H interval, and atrioventricular (AV) nodal effective refractory period. The H-V interval was mildly prolonged in two patients, but the dynamic AV nodal conduction was preserved (1:1 conduction during right atrial stimulation at a cycle length of 400 ms) in all the Chagasic patients. The ventricular parameters were within normal limits, and no sustained ventricular arrhythmia could be induced. CONCLUSIONS: Patients with mild acute Chagasic myocarditis may suffer from electrical abnormalities and arrhythmias that are more evident at the supraventricular level and the AV junction.
Acute Disease↗
Phase II trial of hepatic arterial infusion of fluorouracil and recombinant human interferon alfa-2b for liver metastases of colorectal cancer refractory to systemic fluorouracil and leucovorin.
PURPOSE: To determine the toxicity, response rate, and survival in patients treated with hepatic arterial infusion (HAI) of fluorouracil (5-FU) plus recombinant human interferon alfa-2b (rIFN-alpha 2b) (Intron-A; Schering-Plough, Inc, Kenilworth, NJ) for colorectal carcinoma (CRC) liver metastases refractory to systemic 5-FU plus leucovorin (LCV). PATIENTS AND METHODS: Forty-eight patients were given a 6-hour HAI of rIFN-alpha 2b 5 MU/m2 followed by an 18-hour HAI of 5-FU, 1,500 mg/m2 daily for 5 days. Twenty-nine patients were treated through percutaneously placed catheters and 19 through implantable infusion pumps (Shiley Infusaid Inc, Noorwood, MA). Treatment cycles were repeated every 28 to 35 days. RESULTS: There were three (6.6%) complete remissions (CRs) and 12 (26.6%) partial remissions (PRs), for a CR plus PR rate of 33.3% among 45 assessable patients (95% confidence interval [CI], 20% to 49%). The median response duration was 7 months, while median survival duration was 15 months. Grade 3 to 4 treatment-related toxic effects included mucositis (40%), neutropenia (42%), and thrombocytopenia (12%). No hepatobiliary toxicity was encountered in any of the patients. Treatment was discontinued because of progressive liver disease in 23 patients and extrahepatic progression in 16, while six patients continue treatment through an infusaid pump. CONCLUSION: HAI of 5-FU plus rIFN-alpha 2b is well tolerated, devoid of hepatobiliary toxicity, and can produce a response rate of 33.3% among patients refractory to bolus intravenous (IV) 5-FU plus LCV. The lack of hepatobiliary toxicity may permit salvage HAI with floxuridine (FUDR) in patients whose liver tumors fail to respond to HAI of 5-FU plus rIFN-alpha 2b. Because diarrhea was not a common side effect of HAI of 5-FU plus rIFN-alpha 2b, it would be of interest to investigate whether alternating HAI of 5-FU and rIFN-alpha 2b with systemic irinotecan (CPT-11) will decrease the incidence of both hepatic and extrahepatic disease progression.
Adult↗
Expandable stents.
Expandable metallic stents are effective in selected patients with malignant or benign airway stenoses. When used for malignant lesions, the primary purpose of the stent is to improve the quality of life; stents are usually chosen for palliation of symptoms in recognition of the low likelihood of success for other therapy. For patients with benign stenoses, the stents provide a permanent source of structural support to alleviate the narrowed segment. The advantages of the expandable metallic stents are as follows: (1) they can be inserted through an endotracheal tube or under local anesthesia with relative simplicity under fluoroscopic guidance; (2) they do not impair the drainage of sputum because ciliary movement is not interrupted; (3) over a period of a few weeks, the meshwork is gradually covered with mucosa as the stent becomes incorporated into the airway wall; (4) ventilation usually is not impaired if the metallic mesh stent covers another nonstenosed bronchus, because the interstices of the stent are nonobstructive; and (5) they are dynamic and continue to expand over time, particularly if concurrent treatment achieves an effect on the lesion that caused stenosis. Disadvantages of the expandable stent include (1) they often are only temporarily effective for tracheobronchial stenosis due to intraluminal tumor or granulation tissue, both of which can grow between the wires; (2) they are considered permanent stents because removal is difficult; and (3) they can be poorly positioned during placement or can become displaced by progressive migration after placement, and they cannot be repositioned. A relative contraindication to insertion is an inflammatory process or infection that can predispose to granulation formation, particularly at the points of maximal contact pressure of the stent to the airway mucosa. In the presence of inflammation, it may be better to use a silicone prosthesis until the inflammatory process subsides and fibrosis occurs. Granulation tissue is less likely to occur in areas of established scar than in areas of acute inflammation. In circumstances in which it is essential that a stent remain only temporarily, an expandable stent should not be inserted in favor of a silicone stent, which can be removed. In the future, expandable stents may have silicone coverings or may be constructed of materials that facilitate removal. Until that time, expandable stents should be considered permanent and nonremovable. Subtle differences exist among the available stents. Standard is low-profile expandable construction from wire mesh. A relatively minor difference is the slightly wider expansibility of the Gianturco stent, a quality that makes it the best suited of the three stents for lesions that involve tracheomalacia. Perhaps the only major difference between the Wallstent and the Gianturco and Palmaz stents is its better ability to conform to tortuous lesions. In an acutely angled stricture, a Wallstent offers a better opportunity for successful placement than other stents. The filamentous meshwork of the Wallstent allows it to bend and conform better to distorted airways. The Gianturco and Palmaz stents have little longitudinal elasticity, which makes them less effective in a tortuous or highly angulated airway stenosis. Expandable stents have demonstrated their efficacy and exposed their limitations in the treatment of airway stenoses. Refinements in design should help to lessen specific disadvantages and problems. Covered expandable stents, a realistic prospect, have specific advantages over standard expandable stents; they will be removable and prevent tumor ingrowth. Current investigative work with such prostheses for the vascular system may provide the foundation for their investigative use in the airway. In essence, two categories of expandable stents are evolving, covered and uncovered, each having unique features adaptable to the specific clinical needs.
Bronchial Diseases↗
What is the role of fine needle biopsy in the diagnosis of lymphoma?
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Biopsy, Needle↗
Comparison of chagasic and non-chagasic myocardiopathies by ELISA and immunoblotting with antigens of Trypanosoma cruzi and Trypanosoma rangeli.
Trypanosoma cruzi associated myocardiopathy, or Chagas disease, continues to be a serious problem in Venezuela, for which there is neither a vaccine nor a cure. In order to learn more about the humoral immune response to trypanosomal antigens, and to try to identify dominant antigens, we used ELISA and immunoblotting to study the reactivity of sera from patients with chagasic and non-chagasic myocardiopathies, against surface and secreted proteins from T. cruzi and T. rangeli. Both species are found in the same insect vector, but only T. cruzi is thought to be pathogenic in vertebrates. The ELISA results fell into three patterns: (1) high reactivity values with both T. cruzi and T. rangeli surface and secreted proteins; (2) high values to T. cruzi but low values with T. rangeli; and (3) high values to T. rangeli and low values with T. cruzi. This finding that some chagasic sera react more strongly against T. rangeli than against T. cruzi is intriguing, and warrants further investigation. When chagasic sera were tested on Western blots of total extracts of T. cruzi and T. rangeli, the pattern of reactive bands was similar against both parasites, but no two sera showed an identical pattern. Furthermore, there was no correlation between a particular immunoblotting pattern and either the antibody titer, or the severity of the disease. Several T. cruzi and T. rangeli antigens were recognized by sera from healthy controls as well as from patients with other tropical diseases endemic in Venezuela. Overall, our results suggest that the humoral immune response to trypanosomal antigens is complex, and no single antigen may be the determining factor in the pathogenesis of chagasic myocardiopathy.
Adult↗
Hepatic arterial infusion of floxuridine, leucovorin, doxorubicin, and cisplatin for hepatocellular carcinoma: effects of hepatitis B and C viral infection on drug toxicity and patient survival.
PURPOSE: To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival. PATIENTS AND METHODS: Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks. RESULTS: Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all). CONCLUSION: HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.
Aged↗
Elevated levels of antibodies against sulphatide are present in all chronic chagasic and dilated cardiomyopathy sera.
A natural anti-sulphatide antibody was found to be present in the serum of every normal individual studied. The reactivity of the antibody was assessed by its interaction with galactosylceramide-I3-sulphate. Antigen-antibody binding was strongly blocked by 1 mM heparin, dextran sulphate and chondroitin sulphate A, and by 5 mM chondroitin sulphate B. Antibodies avidly absorb to rabbit erythrocytes, but discretely to rat erythrocytes, suggesting that they are different from galactocerebroside antibodies. Elevated levels of sulphatide antibodies were present in all of 102 chronic Trypanosoma cruzi-infected patients studied, but not in other patients having cutaneous or visceral leishmaniasis, T. rangeli infection or several other protozoal, helminthic or mycotic infections. Interestingly, 100% of 40 dilated cardiomyopathy patients also have elevated levels of sulphatide antibodies. As T. cruzi is rich in galactocerebroside sulphate, it is proposed that in chagasic patients this glycolipid could act as an immunogen, inducing elevated titres of sulphatide antibodies, which could be important in the pathogenesis of cardiac or peripheral nerve symptoms.
Adolescent↗
High lipoprotein(a) in children from kindreds with parental premature myocardial infarction.
In 98 children from 98 kindreds, 49 with and 49 without parental premature myocardial infarction (age < or = 45 y), our specific aim was to determine whether, and to what degree, lipoprotein(a) [Lp(a)] and other atherogenic lipids and lipoproteins might be overexpressed in children from premature infarction kindreds. Median Lp(a) (270 mg/L) in case boys was nearly twice that in control boys (140 mg/L) (p < or = 0.001). In a logistic regression model including age, Quetelet index (relative ponderosity), Lp(a), apo A1, apo B, triglyceride, and pubertal status, the 24 case boys had higher Lp(a) (p = 0.03), higher triglyceride (p = 0.036), and marginally lower apo A1 (p = 0.06) than the 26 control boys. Median Lp(a) in case girls (200 mg/L) was much higher than in control girls (150 mg/L) (p < or = 0.01). In a logistic regression model including age, Quetelet index, Lp(a), apo A1, apo B, triglyceride, and menarchal status, Lp(a) was higher (p = 0.02), apo B was marginally higher (p = 0.07), and apo A1 was lower (p = 0.008) in 25 case girls than in 23 control girls. Reflecting familial clustering of major lipid-lipoprotein risk factors for coronary heart disease, children from kindreds with premature parental myocardial infarction were distinguished from children from control kindreds by high Lp(a) and also had higher apo B and triglyceride and lower apo A1 levels.
Adolescent↗
From protest to productivity: the evolution of indigenous federations in Ecuador.
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Agriculture↗
Effect of physical training on lipids, lipoproteins, apolipoproteins, lipases, and endogenous sex hormones in men with premature myocardial infarction.
In 17 men, aged 27 to 54 years, with myocardial infarction 2 to 10 months before the current exercise study, we aimed to determine whether 3 months of exercise training, at a level designed to elevate high-density lipoprotein cholesterol (HDLC), would be associated with changes in endogenous sex steroid hormones and postheparin lipoprotein and hepatic lipases, and whether the changes in sex hormones, lipids, lipoproteins, apolipoproteins, and physical activity were interrelated. Supervised bicycle ergometry, 30 minutes, 3 days per week, eliciting 75% of maximum heart rate, produced a significant training effect, with a 26% increase in the duration of the exercise test at a standardized, submaximal workload (P less than or equal to .001), and a reduction in heart rate measured at a standardized submaximal workload, P = .08. After 3 months' training, mean HDLC increased 23% (30 to 37 mg/dL), P less than or equal to .001, mean apo A2 increased 19% (43 to 51 mg/dL), P less than or equal to .001, and the ratio of total cholesterol (TC) to HDLC decreased 26% (P less than or equal to .01), while estradiol (E2) levels decreased 45% (50.1 to 27.8 pg/mL), P less than or equal to .0001. After 1 and 2 months' exercise, TC (12% [P less than or equal to .001], 11% [P less than or equal to .01]), and low-density lipoprotein cholesterol (LDLC) (13% [P less than or equal to .01], 12% [P less than or equal to .01]) were reduced. Hepatic lipase decreased 16% (P less than or equal to .01) and 16% (P less than or equal to .05) after 1 and 3 months' exercise. There were no significant changes in apo A1, lipoprotein lipase, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), or weight. By stepwise regression analysis, after 3 months' training, 66% (P = .0025) of the variance for the increase in HDLC from baseline to day 90 was accounted for independently by a decrease in triglyceride (F = 13.2, P = .003), by reduced heart rate on a fixed submaximal load (F = 12.7, P = .0035), and by a decrease in hepatic lipase (F = 5.5, P = .036). A modest, achievable exercise program can have significant cardiovascular benefit for men after myocardial infarction by ameliorating their hyperestrogenemia, reducing TC and LDLC, improving the TC to HDLC ratio, and elevating HDLC and apo A2. The increment in HDLC was related independently to improved capacity to sustain submaximal exercise and to exercise-induced reductions in triglyceride and postheparin hepatic lipase.
Adult↗
[Ventricular mechanics and cardiac arrhythmias in patients with chagasic and primary dilated cardiomyopathy. Echo-electrocardiographic follow-up].
PURPOSE: To determine the prognostic significance of several parameters of left ventricular mechanics and of complex ventricular arrhythmias. PATIENTS AND METHODS: 184 chronic chagasic and 85 primary dilated cardiomyopathy patients were submitted to non-invasive and invasive studies, including Holter monitoring and "M" mode echocardiogram and followed for a maximum of 8 years. RESULTS: Finding of a depressed left ventricle (LV) systolic function (% AC) was the most important independent prognostic factor in both groups of patients. The presence of complex ventricular arrhythmias had an additional, but very limited, independent prognostic importance, observed only in chagasic patients with depressed LV systolic function. When patients with similar degrees of left ventricular systolic dysfunction, inadequate hypertrophy or increased afterload were compared, chagasic patients had significantly worse prognosis than those with primary dilated cardiomyopathy. This is partly attributed to higher prevalence of complex ventricular arrhythmias. CONCLUSION: The higher prevalence of complex ventricular arrhythmias in patients with chronic Chagas' disease may explain the prognostic differences between the groups.
Arrhythmias, Cardiac↗
Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group.
Sixty patients with extremity osteosarcoma were treated with intraarterial cisplatin. This was followed by surgical resection (amputation or limb salvage) and postoperative adjuvant chemotherapy utilizing two different protocols. Seventy-five percent of patients achieved an initial response. Overall disease-free survival was 58%. The number of patients treated with limb-salvage surgery gradually increased to the extent that 80% of newly-registered patients achieved a response and were subjected to limb salvage. Disease-free survival was 48% in amputation and 68% in limb salvage. The only factors found to have prognostic significance in determining disease-free survival were extent of tumor destruction induced by preoperative chemotherapy and tumor size.
Adolescent↗