Picture of the month. First branchial arch syndrome.
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Biomedical subjects
Publications and source records attributed to M Garrido.
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This work is part of a project to develop an expert system for automated classification of the sleep/waking states in human infants; i.e. active or rapid-eye-movement sleep (REM), quiet or non-REM sleep (NREM), including its four stages, indeterminate sleep (IS) and wakefulness (WA). A model to identify these states, introducing an objective formalisation in terms of the state variables characterising the recorded patterns, is presented. The following digitally recorded physiological events are taken into account to classify the sleep/waking states: predominant background activity and the existence of sleep spindles in the electro-encephalogram; existence of rapid eye movements in the electro-oculogram; and chin muscle tone in the electromyogram. Methods to detect several of these parameters are described. An expert system based on artificial ganglionar lattices is used to classify the sleep/waking states, on an off-line minute-by-minute basis. Algorithms to detect patterns automatically and an expert system to recognise sleep/waking states are introduced, and several adjustments and tests using various real patients are carried out. Results show an overall performance of 96.4% agreement with the expert on validation data without artefacts, and 84.9% agreement on validation data with artefacts. Moreover, results show a significant improvement in the classification agreement due to the application of the expert system, and a discussion is carried out to justify the difficulties of matching the expert's criteria for the interpretation of characterising patterns.
Mesenteric venous thrombosis has not been reported after an appendicectomy in the pediatric literature. We report on a special and very unusual complication in a girl who presented mesenteric venous thrombosis (MVT) following an appendicectomy for gangrenous appendicitis. The early diagnosis of this entity is vital in order to start the anticoagulation treatment which could allow preservation of bowel viability. The therapy should be continued for a long time to decrease the risk of relapse.
Monica Garrido, an important personality of the Argentine culture, was chosen as a member of the Executive Council of the ICOM. That is the reason her important work in the cultural life of her Mother Country is described here.
Neoplastic transformation of epithelial cells is commonly associated with alterations in the expression of mucin genes. The mechanisms involved in this process are largely unknown. MUC6, isolated from a stomach cDNA library, is mainly expressed in stomach antral glands, as detected by using in situ hybridization and immunohistochemistry. We examined MUC6 expression in normal and pathological breast tissues using immunohistochemistry with MUC6-specific antibodies and in cultured breast cancer cells using immunocytochemistry and Northern blotting. MUC6 was generally not detected in normal breast (1/11) but was detected in fibrocystic disease without atypia (7/17, 41%), in atypical fibrocystic disease (11/11, 100%) and in carcinoma (57/60, 95%). To study the mechanisms involved in mucin gene up-regulation in breast cancer, we examined baseline, growth-related and steroid-induced levels of MUC1, MUC3 and MUC6 in 4 breast cancer cell lines, 2 of which express estrogen receptors. MUC6 levels were up-regulated at post-confluence in 2/4 cell lines, whereas no changes were detected for the other mucin genes examined. MUC6 and MUC3 were constitutively expressed, and steroid-induced, in BT-474 and MCF-7 cells, respectively. As a control, pS2 was induced in both cell lines. Our results indicate that (1) MUC6 is overexpressed in breast cancer and in benign breast disease, (2) in vitro, MUC6 and MUC3 are up-regulated by steroids and (3) abnormal expression of MUC6 in breast cancers may, in part, be explained by hormonal changes associated with tumor development.
The subcommissural organ of vertebrates secretes glycoproteins into the third ventricle that condense to form Reissner's fiber (RF). Antibodies raised against the bovine RF-glycoproteins reacted with the floor plate (FP) cells of two teleost (Oncorhynchus kisutch, Sparus aurata) and two amphibian (Xenopus laevis, Batrachyla taeniata) species. At the ultrastructural level, the immunoreactivity was confined to secretory granules, mainly concentrated at the apical cell pole. In the rostro-caudal axis, a clear zonation of the FP was distinguished, with the hindbrain FP being the most, or the only (Batrachyla taeniata), immunoreactive region of the FP. In all the species studied, the caudal FP lacked immunoreactivity. Both the chemical nature of the immunoreactive material and the rostro-caudal zonation of the FP appear to be conservative features. Evidence was obtained that the FP secretes into the cerebrospinal fluid a material chemically related to the RF-glycoproteins secreted by the subcommissural organ. Thus, in addition to being the source of contact-mediated and diffusible signals, the FP might also secrete compounds into the cerebrospinal fluid that may act on distant targets.
Mesenteric venous thrombosis (MVT) after appendicectomy has not been reported in the pediatric literature. This complication is associated with significant morbidity and mortality rates in adults. The report of this case attempts to analyze the features found in an appendicectomized child documented by radiological examination and surgery before and after starting heparin therapy. Anticoagulation treatment should be started as soon as possible and continued for a long time to decrease the risk of relapse.
BACKGROUND: Pharmacological inhibition of arachidonic acid metabolism has proven therapeutically useful in the prevention of cardiovascular events. METHODS: We have investigated the ability of Bay u 3405, a synthetic thromboxane antagonist, to interfere with platelet aggregation and arachidonic acid metabolism. The antiplatelet action was also analysed in a perfusion system in which vascular subendothelium was exposed to circulating human blood (10 min; shear rate = 800 s-1). Platelet interactions were morphometrically analysed and results compared with those obtained in studies with blood from donors taking aspirin (acetylsalicylic acid, ASA) (500 mg day-1). The additional effect of Bay u 3405 on the antiplatelet action of ASA was also evaluated. RESULTS: Bay u 3405 caused a dose-dependent inhibition of platelet aggregation induced by U46619 with a maximal effect at concentrations > or = 0.01 microgram mL-1. Higher concentrations (> or = 0.05 micrograms mL-1) also inhibited aggregations induced by ADP or collagen. Bay u 3405 did not interfere with platelet arachidonic acid metabolism. In perfusion studies, Bay u 3405 (0.01 microgram mL-1) significantly decreased the total surface of the vessel covered by platelets (%CS = 18.7 +/- 1.09 vs. 24.4 +/- 1.94; P < 0.05) and the formation of large aggregates %T = 7.5 +/- 0.87 vs. 19.3 +/- 1.61; P < 0.01). ASA treatment reduced platelet aggregate formation (%T = 13.7 +/- 2.06; P < 0.05) but did not affect the total surface covered by platelets. The in vitro addition of Bay u 3405 to blood from ASA-treated donors further reduced the formation of large aggregates (%T = 2.7 +/- 0.79; P < 0.01 vs. ASA). CONCLUSIONS: In vitro effect of Bay u 3405 on platelet function were superior to those observed with ASA. The thromboxane antagonism antagonism provided by Bay u 3405 further enhanced the inhibition of platelet aggregate formation found after ASA treatment.
Two putative substitutes for fresh endothelial cell (EC) extracellular matrix (ECM), frozen ECM and Matrigel, were studied using a parallel-plate perfusion system and platelet deposition was evaluated morphometrically. Coverslips covered with ECM were stored frozen at-30 C for 0 (fresh ECM), 1, 2, 3 or 4 weeks. The ability of frozen ECM to support platelet adhesion after freezing was analyzed under three experimental approaches, perfusing blood: (i) at different shear rates; (ii) on a highly reactive ECM obtained from stimulated EC; and (iii) on ECM incubated with a monoclonal antibody against laminin (LM). Matrigel, alone or mixed with different fractions of wet cryoprecipitate, was layered on coverslips as a thin uniform coat, and perfused, as was done with the frozen ECM. Platelet deposition onto fresh ECM was 21.3 1.5%, 25.5 2.1% and 30.8 2.4% (at shear rates of 300, 800 and 1300/s, respectively) and 40.0 3.8% in PMA stimulated ECM perfused at 800/s. Values obtained on frozen ECM did not vary from those obtained using fresh ECM. Results from perfusion studies using ECM preincubated with an anti-laminin antibody and observations from immunofluorescence studies indicated that the presence and distribution of the adhesive proteins in frozen ECM were similar to those observed on fresh ECM. Platelet deposition on Matrigel was practically absent. Addition of a 20% cryoprecipitate fraction partially restored its thrombogenicity. Our results indicate that when ECM is kept frozen for up to 4 weeks, it behaves as fresh ECM in perfusion studies. On the contrary, Matrigel is not a suitable substrate to support platelet attachment under flow conditions.
Iron deficiency anemia has long been thought to have effects on the central nervous system (CNS). Finding direct evidence of this in human infants, however, has been challenging. Auditory brainstem responses (ABRs) provide a noninvasive means of examining an aspect of the CNS that is rapidly maturing during the age period when iron deficiency is most common. ABRs represent the progressive activation of the auditory pathway from the acoustic nerve (wave I) to the lateral lemniscus (wave V). The central conduction time (CCT, or wave I-V interpeak latency) is considered an index of CNS development because myelination of nerve fibers and maturation of synaptic relays lead to an exponential reduction in the CCT from birth to 24 mo. In 55 otherwise healthy, 6-mo-old Chilean infants (29 with iron deficiency anemia and 26 nonanemic control infants), the CCT was longer in those who had been anemic at 6 mo, with differences becoming more pronounced at 12- and 18-mo follow-ups despite effective iron therapy. The pattern of results--differences in latencies but not amplitudes, more effects on the late ABR components (waves III and V), and longer CCTs (as an overall measure of nerve conduction velocity)--suggested altered myelination as a promising explanation, consistent with recent laboratory work documenting iron's essential role in myelin formation and maintenance. This study shows that iron deficiency anemia in 6-mo-old infants is associated with adverse effects on at least one aspect of CNS development and suggests the fruitfulness of studying other processes that are rapidly myelinating during the first 2 y of life.
We report three cases of esophageal obstruction due to solidification of enteral feed refluxed from the stomach in patients being fed through a nasogastric tube. All three patients were administered sucralfate continuously by tube. The few previous descriptions of this rare complication have also implicated sucralfate with its pathogenesis. Given its clinical importance and the growing use of long-term enteral nutrition, this adverse event needs to be considered.
A 12-year-old girl was taken to the Virgen Macarena Universitary Hospital in Seville, Spain, complaining of abdominal pain, nausea, palpitations, and difficulty in breathing. Her school teacher informed that the girl collapsed after a 100-m race at sports in school. Emergency rescue personnel found the patient pale, in a cold sweat, with low peripheral perfusion. Initial ECF revealed supraventricular tachycardia (150 bpm), right bundle branch block and left anterior hemiblock that, eventually, progressed to full cardiac arrest. At autopsy, an isolated multiple congenital anomaly of the left coronary artery was found (initial segment anomaly; course anomaly and tunneled coronary artery anomaly). In our opinion, this appears to be the first reported case of exercise-related sudden cardiac death, due to an isolated multiple congenital anomaly of the left coronary artery (at the origin, on the course and at the termination).
OBJECTIVE: To describe the surgical procedure of an orthotopic heart transplantation in a recipient with persistent left superior vena cava and atresia of right superior vena cava. EXPERIMENTAL DESIGN: Case report. PATIENT: A 43 year old male with persistent left superior vena cava, atresia of the right superior vena cava and dilated cardiomyopathy. INTERVENTIONS: Orthotopic heart transplantation with selective cannulation of the left superior vena cava via recipient coronary sinus for cardiopulmonary bypass. RESULTS: No perioperative complications, satisfactory postoperative course. No rejection episodes at 7 months postoperative with non invasive procedure surveillance. CONCLUSION: Technique described to preserve left superior vena cava is a useful alternative for this patient with no surgical complications.
Calcium channel blockers have complex actions on aqueous humour dynamics that seem to depend on the route of drug administration. When applied topically, verapamil and nifedipine effectively lower intraocular pressure. However, these drugs also produce a slight reduction in aqueous humor outflow through the trabecular meshwork whereby they could modify the effect of other drugs on intraocular pressure. As calcium channel blockers could be effective in the management of ocular hypertension and low-tension glaucoma, the aim of the present work was to assess the interaction between verapamil and timolol when both drugs are topically applied to the eye of albino rabbits. Intraocular pressure was measured with a manual applanation tonometer. The effects of 5-6 different doses of each drug alone and the effects of five mixtures of both drugs at fixed concentration ratios (timolol: verapamil 4:1, 2:1, 1:1, 1:2 and 1:4) were evaluated. After measuring baseline intraocular pressure, one 50 microliters drop of the different solutions was instilled in the left eye. Measures of the intraocular pressure were repeated at intervals of 30 min until the maximal effect was reached. Each set of experiments was carried out in a group of 9-11 rabbits. Dose-response curves were fitted with a nonlinear regression microcomputer programme. The median effect plot was constructed as proposed by Chou and Talalay (1981, 1983, 1984). In order to analyse the nature of the interaction between both drugs, the observed effect was compared with the theoretically expected one and the combination indices, that relate the doses of verapamil and timolol present in the mixtures with the doses of both drugs separately which are equieffective with the combination, were calculated. The effects of verapamil and timolol followed the principle of the mass action law when administered alone. Nevertheless, no adequate dose-response relationship was obtained when the mixtures of both drugs were applied. In general, the observed effects were lower than the expected ones. Combination indices also indicate the presence of antagonism, except for the lowest concentrations of mixtures where verapamil predominates. In this case, combination indices suggest summation of effects or synergy. Both drugs seem to decrease intraocular pressure by reducing aqueous humor secretion through different mechanisms. However, due to the reduction of aqueous humor outflow caused by verapamil, the ocular hypotensive effect of timolol may be antagonized when high doses of verapamil are administered.
The case notes of 394 adults with bleeding disorders registered at our centre together with those of the 72 patients who had died since 1971 were reviewed. 36/72 deceased patients had evidence of HCV infection. Liver decompensation was present at time of death in six. 274 (70%) of the currently registered patients had received factor concentrate or cryoprecipitate and 174 of these were screened for HCV infection. 76% of tested patients were RIBA positive. 87% of RIBA-positive patients were RT-PCR positive. 50 RIBA-positive patients, including nine who were HIV infected, have undergone percutaneous liver biopsy following appropriate factor infusion with no complication. The biopsy was assessed using a Histological Activity Index (HAI) ranging from 0 to 13. Patients with HAI > or = 6 were offered treatment with interferon. Patients with HAI < 6 were followed up with a view to re-biopsy in 2-3 years to assess progression. The median HAI was 4.5 (range 0-10) with HAI > or = 6 in 13 cases (27%). HAI was not correlated with duration of infection. haemophilia severity. RT-PCR status. HIV status or HCV genotype. Liver biopsy, a safe procedure in our hands, is an important investigation in HCV-infected patients to assess suitability for interferon therapy.
The clinical effectiveness of platelet transfusion in refractory patients is still a subject of debate. We have evaluated the possible hemostatic effect of platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet counts were less than 20,000/microliters. Platelet concentrates were always obtained by apheresis procedures from incompatible donors. The posttransfusion platelet recovery was greater than 15% only in 3 cases. In the first 6 patients, measurements of bleeding time performed immediately before transfusion were in all cases longer than 30 min and did not change significantly 10 and 60 min after platelet transfusions. In all patients, ex vivo perfusion experiments with Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were performed immediately before and 10 and 60 min after transfusion. No difference in platelet deposition onto the subendothelial surface was observed after platelet transfusion. Unexpectedly, the deposition of fibrin on the subendothelial surface was statistically augmented in the posttransfusion studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed statistically significant elevations (p < 0.01) in the posttransfusion samples (31.9 +/- 12.6 vs. baseline 5.8 +/- 1.7 ng/ml), not justified by TAT levels in the transfused material (2.3 +/- 0.17 ng/ml). Transfusion of incompatible platelets to refractory patients may activate coagulation mechanisms in the absence of an increase in peripheral platelet count.
BACKGROUND & AIMS: Among the human mucin complementary DNAs thus far identified, two (MUC5AC and MUC6) were cloned from stomach libraries. This study examines the distribution of MUC6 in normal tissues and compares it with that of MUC5AC as well as with the expression of Lewis blood group antigens. METHODS: Affinity-purified rabbit antibodies detecting epitopes within the repetitive sequence of MUC5AC and MUC6 were used in enzyme-linked immunosorbent assays and immunohistochemical assays. RNA expression was analyzed by in situ hybridization. Double-labeling immunofluorescence was used to study apomucin and Lewis antigen coexpression. RESULTS: MUC6 is detected in the stomach, colon, gallbladder, and endocervix. Two patterns of staining are observed, perinuclear and diffuse cytoplasmic, possibly reflecting differences in MUC6 glycosylation. Using both immunohistochemical assays and in situ hybridization on stomach tissue sections, MUC6 is expressed mainly in antral mucous cells, whereas MUC5AC is detected mainly in the superficial epithelium and neck glands. In antral mucosa, MUC6+ cells express Lewis(y), whereas MUC5AC+ cells express Lewis(b) and sialyl-Lewis(a). CONCLUSIONS: It was concluded that MUC6 has a distinct tissue distribution pattern, different from that of MUC1-MUC5; MUC5AC and MUC6 are expressed by different cellular populations in normal stomach; and in this tissue, MUC5AC+ cells and MUC6+ cells show different patterns of Lewis antigen expression.