Estudio piloto de utilización deantifúngicos sistémicos en el HospitalClínico San Carlos. Propuesta de unmétodo de estudio / Pilot Drug Utilization Study of systemic antifungal agents in the Hospital Clínico San Carlos. Proposal of a study method

Introducción. El estudio propone definir una metodologíade evaluación del uso habitual de antifúngicos sistémicosy ponerla a prueba en un estudio piloto con el fin de facilitarel diseño de estudios de mayor tamaño.Método. Se diseñó en un Estudio de Utilización deMedicamentos, piloto, observacional, de prescripción-indicación.Se propuso una definición de tipo de tratamiento antifúngico(microbiológico, empírico y uso profiláctico) utilizandolos criterios de la EORTC (European Organization for Researchand Treatment of Cancer), la clínica del paciente y la evidenciamicrobiológica, conforme a las pautas de diagnóstico en lapráctica clínica habitual. La adecuación de los tratamientos sevaloró según tres patrones de comparación: ficha técnica, recomendacioneshospitalarias y comité de expertos.Resultados. Se recogieron 60 prescripciones de antifúngicos.39 casos fueron de fluconazol, 6 de itraconazol, 5 deanfotericina liposomal, 5 de caspofungina y 5 de voriconazol.El inicio del tratamiento se realizó en 28 casos como tratamientomicrobiológico (46,7%), en 22 casos como empírico(36,7%) y en 7 casos como uso profiláctico (11,7%). La indicaciónde tratamiento antifúngico se consideró adecuada enmás de un 90% de los casos para los tres patrones de comparación,mientras que adecuación de la selección osciló entreun 75 y un 83%.Conclusiones. El método propuesto para la definición deltipo de tratamiento antifúngico según criterios aplicables en lapráctica clínica se considera satisfactorio y se propone para suempleo en un estudio de mayor tamaño. Para todos los antifúngicosy patrones de comparación, la evaluación resultó conun alto grado de adecuación, sin embargo no resulta fácil sistematizarlas condiciones de utilización de los antifúngicos, debidoa la heterogeneidad de los pacientes e indicaciones (AU)

Introduction. The study aims to define a method forthe evaluation of the usage of systemic antifungal agents,and test it, in order to be able to develop larger studies.Method. Drug Use Study, pilot, observational, prescription-indication. We proposed a definition of antifungaltype of treatment using as host factors the EORTC(European Organization for Research and Treatment ofCancer) criteria, the patient’s clinical data as well as anyevidence of fungal infection. Adequate use was evaluatedby three standards of comparison: summary of productcharacteristics, hospital recommendations and an experts’committee.Results. 60 antifungal prescriptions were recovered:fluconazole: 39; itraconazole: 6; liposomal amphotericinB: 5; caspofungin: 5; voriconazole: 5. Treatment wasstarted as follows (N;%): microbiological (28;46.7), empirical(22;36.7) and prophylactic use (7;11.7). The indicationfor antifungal treatment was considered adequatein more than 90% of the cases for the three standards ofcomparison, whereas selection in 75-83% of the cases.Conclusions. The method is considered satisfactoryfor the evaluation of antifungal treatments and is proposedfor being used in larger studies. For all the antifungalagents evaluated, a high degree of appropriateness of usewas found, though some conditions are considered improvable (AU)

[Pilot Drug Utilization Study of systemic antifungal agents in the Hospital Clínico San Carlos. Proposal of a study method]. / Estudio piloto de utilización de antifúngicos sistémicos en el Hospital Clínico San Carlos. Propuesta de un método de estudio.

INTRODUCTION: The study aims to define a method for the evaluation of the usage of systemic antifungal agents, and test it, in order to be able to develop larger studies. METHOD: Drug Use Study, pilot, observational, prescription- indication. We proposed a definition of antifungal type of treatment using as host factors the EORTC (European Organization for Research and Treatment of Cancer) criteria, the patient's clinical data as well as any evidence of fungal infection. Adequate use was evaluated by three standards of comparison: summary of product characteristics, hospital recommendations and an experts' committee. RESULTS: 60 antifungal prescriptions were recovered: fluconazole: 39; itraconazole: 6; liposomal amphotericin B: 5; caspofungin: 5; voriconazole: 5. Treatment was started as follows (N;%): microbiological (28;46.7), empirical (22;36.7) and prophylactic use (7;11.7). The indication for antifungal treatment was considered adequate in more than 90% of the cases for the three standards of comparison, whereas selection in 75-83% of the cases. CONCLUSIONS: The method is considered satisfactory for the evaluation of antifungal treatments and is proposed for being used in larger studies. For all the antifungal agents evaluated, a high degree of appropriateness of use was found, though some conditions are considered improvable.

Tratamiento del cálculo coraliforme: ¿monoterapia con ESWL? / Treatment of the choraliform calculus: ESWL therapy?

La monoterapia con ESWL del cálculo coraliforme constituye un punto de controversia habitual en la bibliografía y en la práctica clínica. Este trabajo presenta la clasificación actual del cálculo coraliforme, así como un protocolo de tratamiento (AU)

Paciente joven afecto de cistinuria y litiasis renal de cistina. Aspectos clínicos y terapéuticos. A propósito de un caso / Young patient with cystinuria and renal lithiasis of cistine. Clinical and therapeutic aspects. About a clinical case

Un enfoque terapéutico adecuado e individualizado es la base fundamental para prevenir la recidiva litiásica en la cistnuria. Al ser un tratamiento de por vida existe una elevada falta de adherencia al mismo, por lo que se requiere de un seguimiento periódico por parte del médico. A pesar de todas las medidas terapéuticas y normas de conducta empleadas, en algunos casos la recidiva litiásica puede persistir (AU)

Identification of missing persons: the Spanish "Phoenix" program.

In 1999, Spain was the first country to officially start a National Program to try to identify cadavers and human remains which could not be identified by the use of traditional forensic approaches. This attempt is called "Phoenix Program". Two independent mitochondrial DNA (mtDNA) databases were generated, which can automatically compare and match identical or similar sequences. One is the Reference Database, with mtDNA sequences from maternal relatives of missing persons, who provide the samples (buccal swabs) voluntarily; the other is the Questioned Database, comprised of mtDNA data of unknown remains and cadavers. Although the first phase of the program (typing of all unidentified human remains) will probably not be completed until December 2003, positive identifications are being made in the interim. To date, more than 1,200 families have contacted Phoenix, and at least 280 reference samples and 48 questioned evidences have been analyzed. When mtDNA matches are found, another independent analysis is performed as a part of the quality control mechanism. Once a match is confirmed (so far in 6 cases), an attempt is made to analyze short tandem repeat (STR) loci. We call for international collaboration to make this effort valuable worldwide.

Aislamiento y mantenimiento in vitro de Plasmodium falciparum

Se aislaron 08 cepas de Plasmodium falciparum a partir de 10 pacientes. Luego fueron adaptadas y mantenidas en cultivo in vitro durante 60 días en eritrocitos humanos grupo O, en medio RPMI 1640 enriquecido con plasma humano grupo O, bajo una atmósfera de 5% de CO2, 5% de O2 y 90% de Nitrógeno y luego preservados a -70ºC.

Eight strains of Plasmodieum Flaciparum, were isolated from 10 patients. They were adapted and mantained in culture during 60 days using human red celis, group O, RPMI 16 40 medium and human plasma, group O, under 5% oxigen and 90% Nitrigen mixed gases. Finally, they were preserved at -70º C.

The effect of deliberate omission of Trinordiol or Microgynon on the hypothalamo-pituitary-ovarian axis.

The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 micrograms + levonorgestrel 50 micrograms: 6 tablets; ethinyl estradiol 40 micrograms + levonorgestrel 75 micrograms: 5 tablets; ethinyl estradiol 30 micrograms + levonorgestrel 125 micrograms: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms: 21 tablets) on the hypothalamo-pituitary-ovarian axis were studied. Thirty-six women were recruited to the study and divided equally between the two types of pill. Medication was begun on the 8th pill-free day of the cycle and continued for 7 days (Group 1), 14 days (Group 2) or 21 days (Group 3). Levels of FSH, LH, estradiol (E2) and progesterone (P) were measured in plasma on alternate days during the final week of pill therapy, and daily for the 7 days after stopping the pill. For the first 2 weeks of pill therapy, follicular activity, as judged by plasma levels of E2, was greater in women taking Trinordiol than in those taking Microgynon, but was similar in both groups by the third week of pill treatment. Five women taking Trinordiol (2 in Group 1 and 3 in Group 2) had plasma levels of E2 in excess of 500 pmol/l whilst taking the pills, and only 1 patient achieved this degree of follicular activity after stopping the tablets. One woman who had taken 7 days of Trinordiol (Group 1) showed a rise of plasma levels of P to 6.8 nmol/l, but luteinization did not occur in any of the remaining 35 women who took Trinordiol or Microgynon. These findings suggest that follicular activity is less completely suppressed by Trinordiol than Microgynon, at least in the first 2 weeks of pill therapy, but that normal ovulation is still a rare event in the week after cessation of either of these pills, even if only 7 days of medication have been taken.

PIP: The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 microgram + levonorgestrel 50 microgram: 6 tablets; ethinyl estradiol 40 microgram + levonorgestrel 75 microgram: 5 tablets; ethinyl estradiol 30 microgram + levonorgestrel 125 microgram: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 microgram + levonorgestrel 150 microgram: 21 tablets) on the hypothalamo-pituitary-ovarian axis were studied. 36 women were recruited to the study and divided equally between the 2 types of pill. Medication was begun on the 8th pill-free day of the cycle and continued for 7 days (Group 1), 14 days (Group 2) or 21 days (Group 3). Levels of FSH, LH, estradiol (E2) and progesterone (P) were measured in plasma on alternate days during the final week of pill therapy, and daily for the 7 days after stopping the pill. For the 1st 2 weeks of pill therapy, follicular activity, as judged by plasma levels of E2, was greater in women taking Trinordiol than in those taking Microgynon, but was similar in both groups by the 3rd week of pill treatment. 5 women taking Trinordiol (2 in Group 1 and 3 in Group 2) had plasma levels of E2 in excess of 500 pmol/l whilst taking the pills, but this level of follicular activity was maintained in only 3 of these women in the 7 "pill-free" days. None of the women taking Microgynon had levels of E2 above 500 pmol/l whilst taking the pills and only 1 patient achieved this degree of follicular activity after stopping the tablets. 1 woman who had taken 7 days of Trinordiol (Group 1) showed a rise of plasma levels of P to 6.8 nmol/l, but luteinization did not occur in any of the remaining 35 women who took Trinordiol or Microgynon. These findings suggest that follicular activity is less completely suppressed by Trinordiol than Microgynon, at least in the 1st 2 weeks of pill therapy, but that normal ovulation is still a rare event in the week after cessation of either of these pills, even if only 7 days of medication have been taken.

Trastornos cardiovasculares en pacientes con malformaciones somaticos turnerianas. / Cardiovascular disorders in patients with Turner's somatic malformations

Se investigaron los trastornos cardiovasculares en 81 pacientes con malformaciones somaticas turnerianas; 68 de ellos eran portadores de un sindrome de Turner y 13 de un sindrome de Noonan. El 7,3% de los pacientes con sindrome de Turner presentaron alteraciones cardiovasculares; tres de ellos hipertension arterial idiopatica (4, 4%) y dos estenosis aortica (2,9%), se hallaron alteraciones electrocardiograficas en 18/63 casos restantes (28,6%), que en 17 consistio en trastornos de la conduccion y en uno fue hipertrofia ventricular izquierda. En el 30,8% de los pacientes con sindrome de Noonan se hallaron alteraciones cardiovasculares; dos de ellos tenian estenosis pulmonar y dos comunicacion interventricular. En 2/9 casos restantes se observo hipertrofia ventricular izquierda en el electrocardiograma. Los resultados de este estudio demuestran la alta frecuencia de anomalias cardiovasculares en el sindrome de Noonan con respecto al sindrome de Turner, y ademas sugieren que los trastornos cardiovasculares son diferentes en estos dos sindromes. El examen cardiovascular puede ayudar al diagnostico diferencial de estas dos enfermedades

Caracteristicas quimicas del semen en un grupo de hombres aparentemente sanos. / Chemical characteristics of semen in a group of apparently healthy men

El estudio quimico del semen realizado en un grupo de 144 hombres normales arrojo los siguientes resultados: acido critico 589,9 +/- 340,2 mg%; fructosa 374,7 +/- 156,5 mg%; acido ascorbico 7,2 +/- 4,0 mg% calcio 34,5 +/- 29,7 mg%; cloruros 163,6 +/- 34,6; magnesio 9,5 +/- 4,1 mg%; sodio 265,4 +/- 43,2 mg%; potasio 102,4 +/- 41,9 mg% y proteinas totales 5,2 +/- 1,8 g/100 ml. Se sugiere la utilizacion de estos valores como referencia de la normalidad en nuestro medio

Caracteristicas quimicas del semen en un grupo de hombres aparentemente sanos. / Cheical characteristics of semen in a group of apparently healthy men

El estudio quimico del semen realizado en un grupo de 144 hombres normales arrojo los siguientes resultados: acido critico 589,9 +/- 340,2 mg%; fructosa 374,7 +/- 156,5 mg%; acido ascorbico 7,2 +/- 4,0 mg% calcio 34,5 +/- 29,7 mg%; cloruros 163,6 +/- 34,6; magnesio 9,5 +/- 4,1 mg%; sodio 265,4 +/- 43,2 mg%; potasio 102,4 +/- 41,9 mg% y proteinas totales 5,2 +/- 1,8 g/100 ml. Se sugiere la utilizacion de estos valores como referencia de la normalidad en nuestro medio

Trastornos cardiovasculares en pacientes con malformaciones somaticos turnerianas. / Cardiovascular disorders in patients with Turner's soatic malformations

Se investigaron los trastornos cardiovasculares en 81 pacientes con malformaciones somaticas turnerianas; 68 de ellos eran portadores de un sindrome de Turner y 13 de un sindrome de Noonan. El 7,3% de los pacientes con sindrome de Turner presentaron alteraciones cardiovasculares; tres de ellos hipertension arterial idiopatica (4, 4%) y dos estenosis aortica (2,9%), se hallaron alteraciones electrocardiograficas en 18/63 casos restantes (28,6%), que en 17 consistio en trastornos de la conduccion y en uno fue hipertrofia ventricular izquierda. En el 30,8% de los pacientes con sindrome de Noonan se hallaron alteraciones cardiovasculares; dos de ellos tenian estenosis pulmonar y dos comunicacion interventricular. En 2/9 casos restantes se observo hipertrofia ventricular izquierda en el electrocardiograma. Los resultados de este estudio demuestran la alta frecuencia de anomalias cardiovasculares en el sindrome de Noonan con respecto al sindrome de Turner, y ademas sugieren que los trastornos cardiovasculares son diferentes en estos dos sindromes. El examen cardiovascular puede ayudar al diagnostico diferencial de estas dos enfermedades

Psychological characterization of testicular feminization syndrome.

Ten cases with testicular feminization syndrome (TFS) diagnosed at the National Institute of Endocrinology and Metabolism, were studied. The patients were interviewed and subjected to the following psychological tests: Raven's Progressive Matrices, the MMPI, the 16PF, and the TAT. Laboratory determinations included: nuclear chromatin, karyotype, FHS, LH, estradiol, testosterone and nitrogen retention test. Intellectual achievement was found normal, and as far as psychological stability is concerned (MMPI) there was no common profile typical of the group. Psychosexual attitudes showed alterations related to acceptance of body image, fears to be unable to maintain the stability of the couple, and lack of a strong maternal drive. Personality profile manifested two outstanding traits in the group: Dominance (E+) and Shrewdness (N+), the former being remarkably high for a female population. A hypothesis is advanced in regard to the psychological alterations of the possible role of partial androgenization of the central nervous system in these patients.

A preliminary pharmacological trial of the monthly injectable contraceptive cycloprovera.

A comparative pharmacological pilot study of the monthly injectable contraceptive CycloProvera was carried out in 11 women in four centres. There were no significant differences in the results between the centres except that the injection-bleeding interval appeared to be shorter in Swedish women than in those in Havana and Mexico. Medroxyprogesterone acetate was detectable in blood for 28 to 62 days after injection of CycloProvera and although follicular activity returned in less than 28 days after injection in many of the women, corpus luteum function was suppressed for at least seven weeks in all women. Most of the women retained a regular menstrual pattern; six of 33 cycles were amenorrhoeic. There was no significant change in any of the biochemical and haematological analyses.

Sterility caused by functional absence of ejaculatory ducts.

Five patients with functional absence of genital excretory ducts are presented, with emphasis on the scarcity of physical and complementary data obtained. The low impairment of spermatogenesis is pointed out. Seminal characteristics are analysed and the diagnostic importance of spermogram data stressed. The importance of the qualitative determination of fructose for the diagnosis of this syndrome is noted, as well as the incidence of this syndrome as the cause of azoospermia and sterility. The existence of a unilateral congenital absence of ejaculatory ducts is demonstrated. Cases of this sort cannot be detected unless a contralateral acquired lesion occurs.

Spermatogenesis in Klinefelter's syndrome.

The results of a study of seminal fluid, chromosomal formula and testicular tissue performed on 32 patients with Klinefelter's syndrome are presented. The significance of the microscopic study of seminal fluid in this syndrome is well emphasized. The possible relationship of the histological pattern to spermatogenic function and chromosomal constitution is discussed. Our conclusions are that most patients were azoospermic and the the volume of the ejaculate was low or absent. The decreased density of seminal fluid was the result of the absence of spermatozoa. The seminal pH remained normal during the study. Finally, we consider that cases showing areas of spermatogenesis with spermatozoa might correspond to a gondal mosaicism we have failed to diagnose.

PIP: The results of an analysis of seminal fluid, chromosomal formula, and testicular tissue performed on 32 men (including 2 prepubertal boys) with Klinefelter's syndrome are presented. 11 patients failed to yield any seminal fluid, and in 12 patients the seminal volume was less than 2 ml. Seminal density was normal in 50% of cases and diminished in the remainder. Azoospermia was noted in 20 cases, aspermia in 11 cases, and oligospermia in 1 case. Histologic study revealed tubular hyalinization and complete lack of cells involving most seminiferous tubules in 20 patients. A nuclear chromatin study revealed a positive pattern in 31 of the 32 patients. Karotype determination showed a 47,XXY formula in 15 of 16 patients studied. The low volume of ejaculate noted in the majority of these men suggests a severe hypoandrogenism and atrophy of the sex accessory glands. The presence of small amounts of fructose in the semen of these patients reaffirms the existence of a certain degree of androgenic function in Klinefelter's syndrome. Small areas of spermatogenesis were also observed in this series, suggesting the possible existence of an XY cellular line in the gonads whose action permits a certain amount of development of the germinal epithelium. Fertility is possible in some such cases. This syndrome is thought to be present in a latent form during early life, until the arrival of puberty brings about testicular alterations. Both prepubertal boys in this series showed immature tubules, populated almost exclusively by undifferentiated cells resembling presertolian cells.