The synthesis of methyl 5-O-benzoyl-2,3-oxazole-D-ribofuranoside, a tetrahydrofuro [3,4-d]oxazole is described. The key step involves the reaction of methyl 3-amino-3-deoxy-5-O-benzoyl-D-ribofuranoside with N,N-dimethylformamide dimethyl acetal with cyclisation to the 2,3-oxazole via a prototropic rearrangement-elimination reaction.

Monosaccharides↗

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Ovarian stimulation protocol and the outcome of in vitro fertilization are not related to the ability of follicular fluid to induce sperm acrosome reaction.

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Acrosome↗

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Antiproliferative effects of delta 24(25) sterol methyl transferase inhibitors on Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies.

We have studied the antiproliferative effects of two sterol analogs previously reported as potent inhibitors of delta 24(25) sterol methyl transferase (E.C. 2.1.1.43) of yeasts and fungi on epimastigotes and amastigotes on Trypanosoma (Schizotrypanum) cruzi, the causative agents of Chagas disease, as well as its chemotherapeutic effects in a murine model of the disease. On the epimastigote form proliferating in liver infusion tryptose medium at 28 degrees C 22,26-azasterol (AZA), a cholestanol analog with a 6-membered aza ring as a side chain produced a dose-dependent reduction of the growth rate up to 3 microM, but at 10 microM complete growth arest and cell lysis took place after 120-144 h. For 24(R,S),25-epiminolanosterol (EIL), complete growth arrest and lysis took place with 6 microM. In both cases the antiproliferative effects were potentiated by the simultaneous incubation of the epimastigotes with inhibitors of sterol C-14 alpha-demethylase such as ketoconazole or SDZ 89,485, as indicated by concave isobolograms and fractional inhibitory concentrations ranging from 0.11 to 0.46. Analysis of the sterol composition in control and treated cells by thin-layer and capillary gas-liquid chromatography coupled to mass spectrometry showed that growth inhibition correlated with the complete disappearance of the native endogenous sterols of the parasite (ergosterol and 24-ethyl analogs) and the accumulation of 24-desalkyl sterols. Against the clinically relevant amastigote form proliferating inside cultured Vero cells at 37 degrees C, AZA eradicated the parasite of 100 nM, while the corresponding concentration for EIL was 300 nM. Synergic effects of both inhibitors when combined with ketoconazole against this form of the parasite was demonstrated using a three-dimensional analytic method which allowed the identification of optimal drug concentrations. Finally, it was found that daily oral administration of AZA at 50 mg/kg/day for a total of 43 doses to mice infected with a lethal inoculum of T. cruzi allowed survival of all treated animals 25 days after infection, while all control (untreated) animals were dead at this point of time. Increased survival correlated with a 90% reduction in parasitemia in the treated animals. The antiparasitic effects of the azasterol were potentiated in combined treatments with ketoconazole. This is the first report of a successful application of a sterol methyl transferase inhibitor as a chemotherapeutic agent in a protozoal infection.

Animals↗

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[Updating Fanconi's anaemia].

Fanconi's anaemia (FA) is an autosomal recessive syndrome associated with chromosomal instability, and hypersensitivity of the DNA to claustrogenic agents. Clinically it presents a progressive marrow insufficiency, different congenital anomalies and an predisposition to malignancy. Eight complementation groups have been defined and the genes corresponding to six of them have been cloned. Recent advances in molecular biology have made it possible to investigate the relationship between the FA genotype and the nature and severity of the clinical phenotype. The treatment of FA is also the object of intense research that is currently centred on the transplant of hematopoyetic progenitors, especially successful in cases of an HLA-identical brother or sister donor, and in gene therapy, which is still in the phase of clinical research.

Clinical Trials as Topic↗

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[Treatment of pain in hospital paediatrics].

The paper presents a review of pain at the paediatric age, which can be considered a question of maximum interest given the novel application of analgesia or other procedures for avoiding and controlling the different types of pain in the course of normal practice during childhood. After a brief introduction on the history of pain and the scarce attention that it has received until recently, the concepts and different actions for dealing with pain are set out, which depend on its aetiology and localisation: pain in oncology, post-operational pain, pain in chronic or acute diseases, pain in intensive care, etc. Tables are presented with the normal doses used at these ages in the different situations required by the child and which the professional might find himself facing. The non-pharmacological attitude is set out as this can be of great use in the initial stages of controlling pain at these ages, and the different forms of sedation and analgesia at the paediatric age are explained, with regard to the medicines employed, the form of administering them and the importance of a multidisciplinary team: paediatricians, child anaesthetists, nursing personnel as well as the necessary technical support for taking the corresponding action.

English Abstract↗

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[Treatment of hepatic hydatid cysts by percutaneous aspiration and hypertonic saline injection: results of a cooperative work].

Percutaneous puncture-aspiration-injection-reaspiration (PAIR) of hydatid liver cysts, was performed in 38 patients 14-80 years old, with a total of 60 liver hydatid cysts. After aspiration under computed tomography guidance, hypertonic saline was injected into the cystic cavities of patients as a scolecidal agent. No major complications were associated with the procedures. In the follow-up period of 18 months, control CT scans of 35 cysts revealed a gradual decrease in cyst size with a mean volume reduction of 66%. Complications included two cases of urticaria, one case of anaphylaxis and one subcapsular hematoma. No mortality occurred. It is concluded that percutaneous aspiration and hypertonic saline injection for liver hydatid cysts appears to be an effective form of treatment and may eventually prove to be an alternative to surgical intervention.

Adolescent↗

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[The usefulness of electrophysiology in a patient undergoing cardiomyoplasty].

The cardiomyoplasty is a new surgical procedure that uses a skeletal muscle electrostimulated in order to reinforce or even substitute partially the cardiac muscle. We present the electrophysiology aspects in a patient with dilated cardiomyopathy that underwent cardiomyoplasty. First the latissimus dorsi muscle was prepared with a neurostimulant ITREL II. During the surgical procedure a dual-chamber pacemaker mode DDD brand CPI was placed. After three months, ablation radiofrequency of the AV node was performed in order to control the atrial fibrillation that caused heart failure. By means of the AV block we obtained synchrony between the ventricular stimulation and the latissimus dorsi muscle, and by this the patient improved. Using the modern pacemakers and radiofrequency we can control the bradyarrhythmias as well as the tachyarrhythmias frequent in patients with dilated cardiomyopathy, increasing the success rate of cardiomyoplasty.

Adult↗

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[Transesophageal echocardiography in the study of intracardiac thrombosis, tumors and vegetations].

Of 200 consecutive patients, studied with transesophageal echocardiography the findings were analyzed with respect to the presence of thrombi, tumors or vegetations. Thrombus formation was detected in 18 patients; their location and associated pathology are described. Tumors were present in 9 cases and in 10 patients endocarditis in native or prosthetic valves. The information obtained by transesophageal echocardiography was compared with transthoracic echocardiographic data. Transoesophageal echocardiography was demonstrated to be more sensitive, especially in the detection of intracavitary masses in the posterior structures of the heart.

Adolescent↗

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[Surgical resection of a focus of ventricular tachycardia guided by endocardial and epicardial mapping].

We describe a case of a 46 years old female with chagasic heart disease. In one year she presented six episodes of sustained ventricular tachycardia, heart rate 230 beats per minute, morphology of RBBB AQRS -60 degrees, with hemodynamic deterioration that needed electrical cardioversion. She was treated with several antiarrhythmic drugs but not good response was obtained. Programmed electrical stimulation was done and it show three different types of ventricular tachycardia, trough pace-mapping the site of the clinical tachycardia was located in the portion inferior and inferior-posterior of the left ventricle that was confirmed by entrainment. Epicardial mapping was performed in 38 ventricular sites following the modified Harken sketch and the location of the site of outlet was confirmed in the posterior base of the left ventricle, at this point the surgical resection was done with no complication. The results were satisfactory. Eight days later programmed electrical stimulation was done and the ventricular tachycardia could not be induced. Six months afterwards the patient is asymptomatic without medical treatment.

Cardiac Pacing, Artificial↗

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[Pulmonary thromboendarterectomy as a treatment of chronic pulmonary arterial hypertension secondary to unresolved pulmonary thromboembolism. A preliminary report].

This is a preliminary report of our initial experience with thromboendarterectomy in the treatment of four patients with chronic major-vessel thromboembolic pulmonary hypertension. Before surgery, these patients all had severe pulmonary hypertension and cor pulmonale as well as significant abnormalities in lung function (mechanics and gas exchange). They were in class III-IV (NYHA). One of our patients died immediately after the procedure as a result of major bleeding. The remaining three surviving patients have shown a remarkable improvement in both, pulmonary hemodynamics and lung function which has been translated in an also significant improvement in their clinical condition. Although there is still a significant risk involved with this procedure, the thromboendarterectomy represents a reasonable and useful therapeutic approach for selected patients with this deadly form of chronic pulmonary hypertension in which other forms of treatment have proved to be unsuccessful.

Adult↗

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[Doppler color transesophageal echocardiography. Report of the first 110 studies carried out at the Ignacio Chávez National Institute of Cardiology].

Transesophageal echocardiography allows views of the posterior structures of the heart. This approach provides additional and complementary information to the transthoracic study, it is also an alternative in those patients with technical limitations for optimal precordial imaging. This study analysis the first 110 cases studied with transesophageal echocardiography in the National Institute of Cardiology Ignacio Chávez. They correspond to patients with valvular heart disease, prosthesis, acute and chronic ischemic heart disease, dissecting aortic aneurysm, cardiomyopathies, thrombus, tumors and masses. As well as paediatric and adult with complex congenital heart disease. The advantages of the transesophageal technique compared with the precordial approach are described.

Adolescent↗