Structural model and functional significance of pH-dependent talin-actin binding for focal adhesion remodeling.

Actin filament binding by the focal adhesion (FA)-associated protein talin stabilizes cell-substrate adhesions and is thought to be rate-limiting in cell migration. Although F-actin binding by talin is known to be pH-sensitive in vitro, with lower affinity at higher pH, the functional significance of this pH dependence is unknown. Because increased intracellular pH (pH(i)) promotes cell migration and is a hallmark of metastatic carcinomas, we asked whether it increases FA remodeling through lower-affinity talin-actin binding. Talin contains several actin binding sites, but we found that only the COOH-terminal USH-I/LWEQ module showed pH-dependent actin binding, with lower affinity and decreased maximal binding at higher pH. Molecular dynamics simulations and NMR of this module revealed a structural mechanism for pH-dependent actin binding. A cluster of titratable amino acids with upshifted pK(a) values, including His-2418, was identified at one end of the five-helix bundle distal from the actin binding site. Protonation of His-2418 induces changes in the conformation and dynamics of the remote actin binding site. Structural analyses of a mutant talin-H2418F at pH 6.0 and 8.0 suggested changes different from the WT protein, and we confirmed that actin binding by talin-H2418F was relatively pH-insensitive. In motile fibroblasts, increasing pH(i) decreased FA lifetime and increased the migratory rate. However, expression of talin-H2418F increased lifetime 2-fold and decreased the migratory rate. These data identify a molecular mechanism for pH-sensitive actin binding by talin and suggest that FA turnover is pH-dependent and in part mediated by pH-dependent affinity of talin for binding actin.

Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial.

The effects of weight loss on erectile function and hormones have not been well studied. The aim of this study was to measure the degree to which sexual function and in particular erectile function and hormonal environment change after substantial weight loss, surgically and non-surgically induced in the morbidly obese male in a prospective randomized long-term controlled trial. Furthermore, how surgery makes a difference when treating morbidly obese men was envisaged in this context. We prospectively studied 20 morbidly obese men for 24 months, divided into two groups: group A included 10 patients who underwent life style modifications (exercise and diet) for 4 months and subsequently gastric bypass, and another 10 patients in group B were kept on weekly follow-up. None of the men were taking phosphodiesterase type-5 inhibitors. All patients underwent International Index of Erectile Function (IIEF)-5 questionnaire, serum oestradiol, prolactin (PRL), luteinizing (LH) and follicle-stimulating (FSH) hormones, free and total testosterone (FT and TT) at baseline (time 0), surgery - 4 months latter baseline (time 1) and final evaluation - 24 months (time 2). From times 0 to 1, group A presented a mean body mass index (BMI) reduction of 12.6 (p < 0.0001), whereas group B, 2.1 (p > 0.05). The BMI reductions between times 0 and 2 were 24.7 (p < 0.0001) and 0.7 (p > 0.05) for groups A and B respectively. BMI average between the two groups was similar at time 0 (p = 0.2142), and different at times 1 (p = 0.0033) and 2 (p < 0.0006). Increase in IIEF-5 score (p = 0.0469), TT (p = 0.0349) and FSH levels (p = 0.0025), and reduction in PRL level (p < 0.0001) were observed in group A from times 0 to 2 and 1 to 2. There were no changes from times 0 to 1. Comparing groups A and B at time 2, IIEF-5, TT and FT increased significantly in group A (p = 0.0224, 0.0043 and 0.0149 respectively). Surgery-induced weight loss increased erectile function quality measured by IIEF-5 questionnaire, increased TT, FT and FSH and reduced PRL levels. The hormonal impact verified could justify the improvement in erectile function. Lifestyle modifications impacted BMI without hormonal or sexual impact in morbidly obese. New studies are warranted in the field to support our data.

Viral phenotype, antiretroviral resistance and clinical evolution in human immunodeficiency virus-infected children.

BACKGROUND: The syncytium-inducing (SI) viral phenotype and the emergence of viral strains resistant to zidovudine have been described in persons infected with HIV, and in some cases they have been associated with poor prognosis. METHODS: HIV isolates obtained from 37 HIV-infected children were analyzed to determine whether the SI viral phenotype and the mutation on the 215 position of the reverse transcriptase (M215) could be used as markers of disease progression. We performed peripheral blood coculture mononuclear cells, and we analyzed the induction of syncytia using the MT-2 cell line. The emergence of mutations on the 215 position was determined by PCR. RESULTS: We found a statistically significant association (P < 0.05) between SI viral phenotype and (1) recurrent serious bacterial infections, (2) absolute CD4+ cell counts <2 SD, (3) progression to AIDS and (4) death. Sixty percent of the children treated with zidovudine developed 215 mutant viral strains without statistically significant association with clinical or immunologic findings. The SI viral phenotype was statistically associated with the presence of the 215 mutation (P < 0.05). CONCLUSIONS: SI viral phenotype is a marker associated with a poor clinical and immunologic progression of the disease and it may facilitate the emergence of mutant strains in children treated with zidovudine.

Allogeneic BMT in a patient with CML and prior disseminated infection by mycobacterium avium complex.

A patient with chronic myeloid leukemia (CML) who developed a disseminated infection by mycobacterium avium complex (MAC) was successfully treated with rifampin, ethambutol, isoniazid, cycloserin and ciprofloxacin. Diagnosis was proven by histologic examination of hepatic biopsy and culture of the liver biopsy material. Two years later the patient underwent allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor. Antimycobacterial prophylaxis to MAC with ethambutol, cycloserin and ciprofloxacin was given throughout the immediate post-transplant period. On day +25 post-BMT secondary prophylaxis was changed to ciprofloxacin and clarithromycin due to hepatic toxicity. Treatment was maintained until day 100 without side effects. There was no evidence of recurrent mycobacteriosis. Eight months after BMT the patient is well, with a good performance status and chronic graft-versus-host disease (GVHD) limited to the oral mucosa. Thus, MAC infection prior to transplant need not be a contraindication to successful BMT.

A scanning electron microscope study of the nematode Spirura dentata (Spiruroidea) with notes on the morphometric variations in a Spanish population of this species.

This work provides a detailed morphological description by optic and scanning electron microscopy of the nematode Spirura dentara (Monnig, 1938), a parasite of Herpestes ichneumon in southern and central Spain, together with an analyses of the morphometric variations within this population. Our findings in adult specimens include some important characters not recorded in previous descriptions, and contradict these in a few details: a) the four denticles arising from the inner wall of the oral opening are double, not simple as reported in the original description, b) four simple denticles are present, each located between the corresponding double denticles and the central protuberance of the pseudolabium, c) lateral crests are present running along the first third of the body in the adult, starting a short distance behind the deirids, and d) the pair of small submedian post-cloacal papillae mentioned in the original description has not been observed. The fourth-stage larva is described for the first time. The relative growth rate (i.e., growth rate with respect to body length) of the reproductive zone was higher in females. In adult males, the growth of the left (longer) spicule was positive, whereas that of the right (shorter) spicule was negative.

[Solitary hepatic carcinoid tumor in a man with prior treatment for rectal adenocarcinoma. Rapid growth without carcinoid syndrome]. / Tumor carcinoide hepático único en un paciente tratado por adenocarcinoma de recto. Crecimiento rápido sin síndrome carcinoide.

We describe a case of hepatic carcinoid tumor that was diagnosed after right hepatectomy. The tumor was initially believed to be metastases from a rectal adenocarcinoma for which surgery had been performed seven years earlier. We highlight the localization of the tumor in the liver only, its large size and rapid growth, as well as the absence of carcinoid syndrome. Diagnostic studies of function and localization are presented. The absence of neoplasia in other locations suggested that this neoplasm was probably a primary hepatic carcinoid tumor. The association of carcinoid tumors with other neoplasms is well-known. However, because of our patient's history and the absence of symptoms, the preoperative diagnosis was incorrect. The definitive diagnosis was confirmed by pathological analysis, allowing specific studies of function and localization to be performed and therapeutic and follow-up measures to be adopted. Although surgery plays a crucial role in the treatment of these tumors, it should be performed in the context of the multidisciplinary management recommended for this disease.

[Evaluation of tissue perfusion by simultaneous non-invasive monitoring of the hemodynamic profile and capnography]. / Evaluación de la perfusión tisular mediante la monitorización simultánea del perfil hemodinámico no invasivo y la capnografía.

OBJECTIVES: To assess the simultaneous variations in blood gases and CO2 tele-expiratory pressure (ETCO2) produced by changes in tissue perfusion in anesthetized patients with stable lung perfusion, alveolar ventilation and metabolic states. MATERIAL AND METHODS: Forty patients were divided into two groups. Group 1 included 20 ASA I patients undergoing orthopedic surgery on the lower extremities. Group 2 included 20 ASA I-III patients undergoing peripheral vascular surgery during which myocardial depression developed after isoflurane administration. The decrease in minute volume was measured in the descending aorta by esophageal ultrasound in both groups. Other hemodynamic parameters were measured by digital plethysmography. ETCO2 was measured by lateral aspiration capnography, and central venous pressure was measured in group 2 by subclavian venous catheter. Measurements were taken before and after release of the tourniquet in group 1, and before and after the decrease in minute volume (> 30%) in group 2. RESULTS: Release of the tourniquet after a mean compression time of 51 +/- 07 minutes produced an increase of 52% (p < 0.001) in minute volume in all patients in group 1; an increase of 23% (p < 0.001) in ETCO2; and a decrease of 60% (p < 0.001) in total vascular resistance. In group 2 a 15% decrease in ETCO2 (p < 0.01) was observed, coinciding with a 35% decrease in minute volume (p < 0.01). CONCLUSIONS: An increase in minute volume produces an increase in ETCO2 while a decrease in minute volume results in a decrease in ETCO2. This means that sharp changes in ETCO2 may be useful in judging the degree of change in tissue perfusion when other parameters like alveolar ventilation, lung perfusion and metabolic rate remain constant.

[Frequency of Chlamydia trachomatis in the cervix of pregnant women during prenatal examinations]. / Frecuencia de Chlamydia trachomatis en el cérvix de pacientes embarazadas en control prenatal.

From February 1993 to October 1995, 80 endocervical samples taken from 80 pregnant patients in pre-natal control were examined in private practice at the Hospital Angeles del Pedregal in Mexico City for purposes of detecting Chlamydia trachomatis by direct inmunoflorecency. Gestational ages ranged from 20 to 39 week. A positive reaction to Chlamydia trachomatis was observed in 10% (8 patients) of the participating patients. Taking into account this frequency it is suggested that this study be a part of prenatal control.

Helminth fauna of Falconiform and Strigiform birds of prey in Galicia, Northwest Spain.

This is a survey of the helminth fauna of 285 individuals of 14 species of birds of prey (Falconiformes and Strigiformes) from Galicia (northwest Spain), namely Buteo buteo, Accipiter nisus, A. gentilis, Milvus migrans, M. milvus, Pernis apivorus, Circus pygargus, Falco tinnunculus, F. peregrinus, F. subbuteo, Tyto alba, Strix aluco, Asio otus and Athene noctua. A total of 15 helminth species were detected, namely 8 nematodes ( Eucoleus dispar, Capillaria tenuissima, Synhimantus laticeps, Microtetrameres sp., Physaloptera alata, Procyrnea leptoptera, Hovorkonema variegatum and Porrocaecum angusticolle), 4 cestodes ( Cladotaenia globifera, Paruterina candelabraria and Mesocestoides sp.), 2 trematodes ( Neodiplostomum attenuatum and Strigea falconis), and 1 acanthocephalan ( Centrorhynchus globocaudatus). The helminth communities observed were basically similar, although there were marked differences in species richness, which was higher in falconiforms (except for A. gentilis) than in strigiforms. More specifically, species richness was highest in B. buteo (13 species), followed by A. nisus (11 species). In the falconiforms, the helminth species present generally exhibited a clear relationship with host diet. In the strigiforms, by contrast, species richness was lower than expected given the host's diet, suggesting that a different explanation is needed.

Reversible bone marrow depression by high-dose piperacillin/tazobactam.

Bone marrow toxicity, mainly neutropenia, has been described as an uncommon secondary effect of most beta-lactams, and it is usually related to large cumulative doses. Although previously described for piperacillin, no cases of marrow depression caused by piperacillin/tazobactam have been reported to date. We report a case of reversible pancytopenia, with evidence of bone marrow depression, which occurred after a 17 d course of piperacillin/tazobactam. The drug was given to an underweight 18-year-old woman, at the usual dosage of 4/0.5 g three times a day. We stress the need for reducing the recommended dosage when treating underweight adult patients, and also of monitoring haematological parameters during prolonged treatments.

[Lymphocytic meningitis. Virologic study. Analysis of the study carried out from 1984 to 1986 (632 cases)]. / Meningitis linfocitaria. Estudio virológico. Análisis de estudio realizado entre 1984-1986 (632 casos).

The experience with the virological diagnosis of lymphocytic meningitis in the Centro Nacional de Microbiología during 3 years (1984-1986) included 632 cases. The most common causative organism was the parotiditis virus (46.9%), particularly in children (64.6%), followed by the non-polio enteroviruses (25.3%). The varicella-zoster virus was the most common organism found in adults (33.3%). We describe some clinical and epidemiological aspects, emphasizing the absence of clinical features suggesting herpesvirus infection in about 50% of cases. Finally, we indicate the study techniques or methods more adequate in each instance (specific IgM detection, isolation techniques or detection of intrathecal antibody production), and we define a study protocol for cases of acute lymphocytic meningitis which permits a high diagnostic yield (44.1-54.9%).

Inmunidad y "stress": sus relaciones con la técnica anestésica / Immunity and stress: their relation with anesthetic technic

Los procedimientos anestésico-quirúrgicos podrían provocar severas modificaciones metabólicas e inmunológicas en la respuesta de adaptación de stress. Hemos estudiado 20 pacientes seleccionados que fueron sometidos a dos tipos diferentes de técnicas anestésicas. En el primer grupo (11 pacientes) el procedimiento fue anestesia raquídea y en el segundo grupo (9 pacientes) anestesia geral. En todos los casos el procedimiento quirúrgico fue herniorrafia inguinal. Los exámenes de laboratorio fueron: nivel de Cortisol plasmático, nivel de inmunologlobulinas, nivel de C3, recuento leucocitario (relativo y absoluto) y recuento de subpoblaciones linfocitarias. En todos los casos el análisis de laboratorio se realizó al inicio y al final del procedimiento quirúrgico, a las 24 horas y a las 72 horas. Los resultados mostraron que los niveles de Cortisol plasmático estaban aumentados al final del procedimiento quirúrgico en pacientes sometidos a anestesia general. No se observaron variaciones significativas del Cortisol plasmático en pacientes sometidos a anestesia raquídea y el recuento periférico de neutrófilos aumentó en ambos grupos de pacientes 24 horas después de finalizar el acto quirúrgico. Los parámetros inmunológicos no muestran variaciones significativas antes o después del procedimiento quirúrgico en ambos grupos de pacientes. Nuestros resultados demuestran que la respuesta neuroadaptativa está sólo presente en los pacientes sometidos a anestesia general y no se correlacionan con modificaciones inmunológicas. Se sugiere que los procedimientos anestésicos por sí mismos no producen alteraciones inmunológicas

Intubacion selectiva y ventilacion unilateral en al resection pulmonar. / Selective intubation and unilateral ventilation in pulmonary resection

Se estudiaron 10 pacientes en los que se realizo anestesia con intubacion selectiva para cirugia pulmonar. Se analizo la repercusion de esta tecnica sobre el intercambio faseoso y el equilibrio acidobasico. En ningun caso se comprobo tensiones parciales de O2 que comprometieran la seguridad de los pacientes. En casos que se utilizo circuito con reinhalacion se detectaron hipercapreas y descensos del pH significativos. Se aconseja patrones ventilatorios que eviten esa situacion. En ningun caso se comprobo la instalacion de atelectasia. Se enfatiza las ventajas de esta tecnica al facilitar las maniobras quirurgicas.

Comparación hemodinámica entre isoflurane y sevoflurane en el paciente quemado / Hemodynamic comparison of isoflurane and sevoflurane in the burn patient

Se estudiaron prospectivamente 27 operaciones en 13 pacientes, con una superficie corporal total quemada media de 21 por ciento (10-57). La edad promedio fue de 37 años (16-78). Se excluyeron pacientes con distress respiratorio y/o con repercusión hemodinámica que requirieran drogas vasoactivas. En todos se obtuvo un perfil hemodinámico continuo, en tiempo real y no invasivo del gasto aórtico (GAM), presión arterial media (PAM), resistencia vasculares sistémicas (RVST) e intervalo tiempo sistólicos (ITS), PePi, LVET y relación PePi/LVET. Se inició la anestesia general con sevoflurane o isoflurane en forma randomizada y, en situación estable, se cambió de agente midiendo a los 30 minutos las eventuales repercusiones hemodinámicas. Ninguna de las diferencias fueron estadísticamente significativas. Todos los valores hemodinámicos medios de ambos agentes estuvieron dentro de los rangos de normalidad para esta etapa de los quemados. Como conclusión, parece no haber diferencias hemodinámicas significativas entre ambos agentes en este tipo particular de pacientes estudiado