Long-term outcomes after robotic sacrocolpopexy in pelvic organ prolapse: prospective analysis.

OBJECTIVE: To evaluate the feasibility and long-term outcomes of our initial series of robot-assisted laparoscopic sacrocolpopexy. METHODS: We conducted a prospective analysis of our series of robotic sacrocolpopexy. INCLUSION CRITERIA: patients with grades III and IV cystocele and or other symptomatic pelvic organ prolapse. We performed a transperitoneal four-trocar technique with the Da Vinci robotic system using two polypropylene meshes for fixation to the sacral promontory. The primary outcome was recurrence; secondary outcomes included operating room time, blood loss, conversion to open surgery, complications and length of stay. RESULTS: 31 consecutive procedures were included. Mean patient age was 65.2 (50-81) years. Mean operating room time was 186 (150-230) min. We converted 1 case to laparoscopy (3.2%). There were two major complications (1 acute myocardial infarction and 1 reoperation for excess tension with syncopes), two minor complications (1 wound infection and 1 ileus) and no recurrences at a mean follow-up of 24.5 (16-33) months. CONCLUSIONS: Robotic sacrocolpopexy could possibly improve with experience after overcoming the learning curve. There is no doubt it is a reproducible technique, but its safety and efficacy still need to be proven. Our initial series demonstrated good outcomes and no recurrences at 24.5 months of follow-up.

Neurotrophin and Trk neurotrophin receptors in the inner ear of Salmo salar and Salmo trutta.

Neurotrophins (NTs) and their signal transducing Trk receptors play a critical role in the development and maintenance of specific neuronal populations in the nervous system of higher vertebrates. They are responsible for the innervation of the inner ear cochlear and vestibular sensory epithelia. Neurotrophins and Trks are also present in teleosts but their distribution in the inner ear is unknown. Thus, in the present study, we used Western-blot analysis and immunohistochemistry to investigate the expression and cell localization of both NTs and Trk receptors in the inner ear of alevins of Salmo salar and Salmo trutta. Western-blot analysis revealed the occurrence of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor (NGF), as well as all three Trk receptors, i.e. TrkA, TrkB and TrkC, the estimated molecular weights of which were similar to those expected for mammals. Specific immunoreactivity for neurotrophins was detected mainly in the sensory epithelia. In particular, BDNF immunoreactivity was found in the maculae of the utricle and saccule, whereas NT-3 immunoreactivity was present in the sensory epithelium of the cristae ampullaris. As a rule the sensory epithelia of the inner ear lacked immunoreactivity for Trks, thus excluding possible mechanisms of autocrinia and/or paracrinia. By contrast, overlapping subpopulations of neurons in the statoacoustic ganglion expressed TrkA (about 15%), TrkB (about 65%) and TrkC (about 45%). The present results demonstrate that, as in mammals and birds, the inner ear of teleosts expresses the components of the neurotrophin-Trk system, but their roles remain to be elucidated.

Lung graft dysfunction in the early postoperative period after lung and heart lung transplantation.

BACKGROUND: We present a retrospective study of 9 years of experience in the management of graft dysfunction in the early postoperative period after lung transplantation (LT) and heart lung transplantation (HLT). MATERIAL AND METHODS: There were 190 LT and HLT (22.63% single LT, 71.05% bilateral sequential LT, and 7.36% HLT) performed from 1993 to 2002. Hemodynamic and respiratory parameters were monitored during the operative technique and critical care for the first 24 hours. We analyzed ischemic time, bypass need, and type of transplant. RESULTS: Lung graft dysfunction occurred in 37.2% of patients, but only in 12.2% was it severe. Nearly all patients were ventilated on a 50% fraction of inspired oxygen during the first 24-48 hours; 61.56% of patients were extubated before the first 5 postoperative day and 38.43% thereafter. The mean ischemia time for the first lung was 220 +/- 28 minutes: for the second lung, it was 378 +/- 31 minutes. The anesthetic time was 500-600 minutes. The variables associated with a significantly increased graft dysfunction were as follows: bilateral LT, and cardiopulmonary bypass requirement. The residence in the intensive care unit (ICU) was longer for patients with graft dysfunction than for those without that problem. Mortality directly related to graft dysfunction was only 4.07%. CONCLUSIONS: A correlation among graft ischemia and early postoperative morbidity and duration of ICU stay did not have a significant impact on mortality.

Tumores estromales gástricos: formas de presentación y opciones quirúrgicas / Gastric stromal tumors: clinical presentation and surgical options

Los tumores estromales representan el 1-3 por ciento de las neoplasias gástricas primitivas. Se pueden presentar a cualquier edad, bajo muy diversas formas clínicas, siendo raro que alcancen un tamaño superior a los 10 cm. Estos raros tumores se encuadran en la actualidad dentro de los denominados tumores del estroma gastrointestinal (GIST´s) , cuya clasificación continúa siendo controvertida. La cirugía es el tratamiento de elección y su extensión viene determinada por el tamaño del tumor, la afectación de órganos vecinos y la presencia o no de metástasis. En casos seleccionados, la cirugía mínimamente invasiva puede llevarse a cabo con excelentes resultados. Presentamos cuatro casos que resumen las distintas formas de presentación clínica de estos tumores así como su manejo terapéutico (AU)

Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty.

BACKGROUND: The Peptide YY (PYY) secretion pattern was assessed in morbidly obese (MO) patients before and after vertical banded gastroplasty (VBG). METHODS: 12 MO patients (10 women, 2 men) age 29-62 years, BMI 50.7 +/- 9.6 kg/m2, treated with a VBG were studied. Before surgery, blood samples were taken in basal conditions of fasting and 10, 15, 20, 30 and 60 min after the ingestion of a semiliquid test meal. This was repeated in the same patients 6 and 12 months after VBG. Blood samples were also taken from 6 healthy non-obese subjects as controls. PYY plasma concentration was measured by radioimmunoassay with I125. RESULTS: There were statistically significant differences between the preoperative PYY concentration in MO patients compared to controls. After a VBG, PYY concentration varied significantly compared to the preoperative levels. There was no significant difference between the PYY concentrations in the MO patients after VBG and the controls. CONCLUSION: PYY concentration is lower in MO patients compared with non-obese. After VBG, PYY concentration gradually rises to the control levels.

[The phospholipase A2 inhibitor, aristolochic acid, inhibits chloride secretion without altering barrier function]. / El inhibidor de la fosfolipasa-A2, el ácido aristolóquico, inhibe la secreción de cloro sin alterar la función de barrera.

AIM: To study the effect of aristolochic acid (AA) and the effect of phospholipase A2 (PLA2) on barrier function and electrogenic chloride secretion in intestinal epithelium. MATERIAL AND METHODS: Electrophysiological studies were performed in the T84 cell line and rat distal colon. Ionic secretion and transepithelial resistance were determined. RESULTS: Exogenous AA increased calcium-stimulated secretion in the T84 cell line. Incubation of rat distal colon in the presence of AA, a PLA2 inhibitor, reduced basal ionic secretion without affecting transepithelial resistance and inhibited ionic secretion stimulated by a cyclic adenosine monophosphate (AMPc) agonist, forskolin. In T84 cells, AA inhibited both carbachol- and forskolin-stimulated secretion. CONCLUSION: PLA2 modulates electrogenic chloride secretion but has no effect on barrier function in the T84 cell line or in rat distal colon.

Lactate metabolism during laparoscopic cholecystectomy: comparison between CO2 pneumoperitoneum and abdominal wall retraction.

Recent reports have implicated CO2 pneumoperitoneum for laparoscopic surgery in the occurrence of postoperative mesenteric ischemia. With this kind of surgery, the increase in blood lactate levels has been attributed to anaerobic metabolism, probably due to tissue ischemia induced by high intraabdominal pressure (IAP). The aim of this study was to evaluate the metabolic repercussion of CO2 pneumoperitoneum during laparoscopic cholecystectomy (LC). This was a prospective randomized study of CO2 pneumoperitoneum (PP group, n = 19) versus abdominal wall retraction (AWR group, n = 15). Demographic data were collected preoperatively. Four-trocar LC was performed with either a CO2 pneumoperitoneum (IAP of 12 mmHg) or abdominal wall retraction (abdominal wall pressure 6-10 kp). Intraoperative and postoperative blood samples were collected and lactate levels determined by enzymatic analysis. Repeated measures analysis of variance (MANOVA) was used for statistical analysis. Significance was evaluated at p < 0.05. The groups were shown to be homogeneous. Lactate concentration, expressed as mean (SD), went from 25.4 (14.4) mg/dl at baseline to 18.9 (13.6) mg/dl 4 hours after surgery in the PP group and from 19.4 (6.1) mg/dl at baseline to 17.8 (14.7) mg/dl in the AWR group. No significant differences were found between groups intraoperatively (p = 0.116) or postoperatively (p = 0.99). Our study did not show significant differences in blood lactate levels during LC with CO2 pneumoperitoneum compared to the same procedure with abdominal wall retraction.

Reduction of glial fibrillary acidic protein-immunoreactive astrocytes in some brain areas of old hairless rhino-j mice (hr-rh-j).

Mutations in the hairless (hr) gene of mice result in hair follicle and other epithelial defects. The hr gene is expressed at high levels in the brain where it probably participates in the survival and maintenance of some neuronal populations, but whether it also supports glial populations of the central nervous system has been not investigated. To clarify this, quantitative immunohistochemistry for astrocytes (glial fibrillary acidic protein (GFAP)) and microglial cells (CD11b macrophage antigen) was used in the brain of a mutant mouse strain, the hairless (hr-rh-j) type, which carries the homozygous hr gene rhino mutation. The glial cell density was assessed in the cerebral cortex, hippocampus, striatum, hypothalamus and cerebellum of young (3 months) and old (9 months) hr-rh-j mice. No significant differences were found between young wild-type and hr-rh-j mice. The density of GFAP immunoreactive astrocytes normally increased as a function of age, but in older hr-rh-j mice there was a severe reduction (P<0.01) in the striatum, hypothalamus, and hippocampus. Conversely, the microglial cells were insensible to aging or to hr-rh-j mutation. These results suggest that the hr gene is involved in the maintenance of the GFAP immunoreactive cells in some cerebral areas. Nevertheless, because these animals do not show any neurological signs, the functional significance of the present findings remains to be established.

The thymus of the hairless rhino-j (hr/rh-j) mice.

The hairless (hr) gene is expressed in a large number of tissues, primarily the skin, and a mutation in the hr gene is responsible for the typical cutaneous phenotype of hairless mice. Mutant hr mouse strains show immune defects involving especially T cells and macrophages, as well as an age-related immunodeficiency and an accelerated atrophy of the thymus. These data suggest that the hr mutation causes a defect of this organ, although hr transcripts have not been detected in fetal or adult mice thymus. The present study analyses the thymus of young (3 mo) and adult (9 mo) homozygous hr-rh-j mice (a strain of hairless mice) by means of structural techniques and immunohistochemistry to selectively identify thymic epithelial cells, dendritic cells, and macrophages. There were structural alterations in the thymus of both young and adult rh-rh-j mice, which were more severe in older animals. These alterations consisted of relative cortical atrophy, enlargement of blood vessels, proliferation of perivascular connective tissue, and the appearance of cysts. hr-rh-j mice also showed a decrease in the number of epithelial and dendritic cells, and macrophages. Taken together, present results strongly suggest degeneration and accelerated age-dependent regression of the thymus in hr-rh-j mice, which could explain at least in part the immune defects reported in hairless mouse strains.

Gasless laparoscopic cholecystectomy is not more time-consuming.

BACKGROUND: Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy (LC), many surgeons have found that, when this option is chosen, more time is needed to prepare for and carry out the surgical procedure. Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide (CO2) pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR). METHODS: We performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR LC group (n = 15). Demographic data were collected preoperatively. LC was performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were considered: (a) time employed to create the surgical field (phase 1) and (b) operating time (phase 2). The chi-square test was used to compare the medians of the two groups. RESULTS: The two groups were homogeneous. Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60 min in both groups (p = 0.76). CONCLUSION: We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time.

Efecto de un inhibidor de las tirosinfosfatasas sobre la secreción de cloro del epitelio intestinal humano / Effects of a tyrosine phosphatase inhibitor on chloride secretion in human intestinal epithelia

OBJETIVO: el transporte transcelular de cloro es el proceso clave en la hidratación del epitelio intestinal. En la actualidad poco se sabe sobre la implicación de las tirosinfosfatasas en la regulación de la secreción basal y activada en el epitelio intestinal humano. El objetivo es investigar los efectos de un inhibidor de las tirosinfosfatasas, el ortovanadato, sobre la secreción de CI en el colon humano. DISEÑO EXPERIMENTAL: electrofisiología. Medida de los cambios en la corriente de cortacircuito por un clamp de voltaje/corriente en mucosa de colon humano y monocapas de una línea celular análoga a las células de las criptas intestinales montadas en cámaras de Ussing modificadas. RESULTADOS: el ortovanadato (1 mM) aplicado en la vertiente serosa ocasionó un incremento de la corriente de cortacircuito en la mucosa de colon humano. La corriente de cortacircuito equivale al movimiento transcelular de cloro. El mismo efecto se observó en monocapas de la línea celular. La respuesta al ortovanadato se ve potenciada por el tratamiento previo de las monocapas con un inhibidor de las tirosincinas, la genisteina, pero sólo cuando se añade a la superficie basolateral del epitelio. Además esta potenciación no se observa si las monocapas epiteliales son tratadas previamente con un agonista del AMPc, la forskolina. CONCLUSIONES: demostramos que las tirosinfosfatasas pueden estar implicadas en la regulación de la secreción epitelial de cloro y que el ortovanadato, un inhibidor de las fosfatasas, estimula el transporte transcelular de cloro en el epitelio cólico humano (AU)

Quantitative study of metals in bile from patients with cholelithiasis.

OBJECTIVE: Biliary lithiasis is a multifactorial phenomenon that is decisively influenced by the composition of bile. We analyzed the presence of eight metals in bile and compared their concentrations in healthy persons and patients with cholelithiasis. METHODS: We studied bile from 119 patients who underwent cholecystectomy because of symptomatic cholelithiasis, and from 25 control subjects in whom the gallbladder was removed for reasons other than cholelithiasis. Metal concentrations were analyzed by atomic absorption spectrophotometry. The subjects were divided into subgroups according to age, sex and type of stone. RESULTS: Bile from patients with cholelithiasis contained significantly less of the essential element magnesium (Mg) and the toxic element lead (Pb) than bile from control subjects. Calcium (Ca) and strontium (Sr) concentrations were also lower in patients with gallstones than in the control group, although the differences were not significant. CONCLUSIONS: Biliary concentrations of Mg and Pb were significantly lower in patients with cholelithiasis than in the control group. The biliary excretion of Ca and Sr was lower in patients than in controls, although the differences were not statistically significant.

Formación del cirujano en cirugía laparoscópica / Laparoscopic training for surgeons

La cirugía laparoscópica es una nueva vía de abordaje quirúrgico que posee una serie de características diferenciales con la cirugía convencional: creación de una cavidad real mediante la introducción de gas y el impacto de éste sobre los órganos intraabdominales, utilización de material sofisticado (óptica, cámara, etc.) y modificación de los sentidos del cirujano en cuanto a su interrelación con la intervención. Se incrementa el detalle y se magnifica el campo, pero se pierde la tercera dimensión. El tacto se modifica de forma sustancial por el tipo de instrumentos, con la pérdida de la sensibilidad estereognóstica (reconocimiento de objetos por el tacto). A la vez, el movimiento manual para la realización de cualquier maniobra quirúrgica es totalmente diferente al de la cirugía convencional. Todo ello significa que la cirugía laparoscópica debe ser aprendida y, por tanto, enseñada de forma diferente a la convencional. La formación del cirujano en cirugía laparoscópica debe realizarse desde los ámbitos teórico, práctico y clínico. Esto incluye el conocimiento del aparataje y de la fisiopatología, el desarrollo de las habilidades en técnicas de disección y sutura en el simulador y el animal de experimentación y, finalmente, en el quirófano, en un inicio como ayudantes para progresar hasta la realización completa de la intervención. Este planteamiento es aplicable tanto a cirujanos formados como a residentes en formación. Los hospitales y servicios de cirugía con responsabilidad en la formación de especialistas deben garantizar la adecuada enseñanza de la cirugía laparoscópica a los nuevos cirujanos para que ésta sea una técnica habitual y no la técnica excepcional (AU)

Estudio cuantitativo de metales biliares en colelitiasis / Quantitative study of metals in bile from patients with cholelithiasis

INTRODUCCIÓN: la litiasis biliar es un fenómeno multifactorial en el que influye de manera decisiva la composición de la bilis vesicular. Analizamos la presencia de ocho metales en bilis y realizarnos un estudio comparativo de la concentración de los mismos en la bilis vesicular de sujetos con colelitiasis y el contenido de estos metales en la bilis de sujetos sanos. PACIENTES Y MÉTODO: estudiamos bilis de 119 pacientes, colecistectomizados por colelitiasis sintomática y la bilis de 25 sujetos control a los que se les extirpó la vesícula por razones diferentes a la litiasis biliar. El análisis de los metales se ha realizado mediante técnicas de espectofotometría de absorción atómica. En el estudio hemos establecido distintos subgrupos en función de la edad, el sexo y el tipo de cálculo hallado. RESULTADOS: nuestros resultados muestran que las bilis de los pacientes con cálculos presentan una excreción biliar signifícativamente menor del metal esencial mayoritario magnesio (Mg) y del metal tóxico plomo (Pb) en relación a la concentración biliar de estos metales en los sujetos sanos. El contenido de calcio (Ca) y estroncio (Sr) biliar de los sujetos con litiasis también es menor que en el grupo control aunque no alcance significación estadística (AU)

[From the laboratory to the clinic: CFTR and the therapeutic options for cystic fibrosis]. / Del laboratorio a la clínica: CFTR y opciones terapéuticas para la fibrosis quística.

Cystic fibrosis is a common lethal heritable disorder, caused by a defect in a chloride channel protein, namely CFTR. After the identification of the gene and its product by positional cloning (on chromosome 7), CFTR has been characterized as a low conductance (8-10 pSiemens) linear chloride channel, which appears to regulate other apical transport proteins. Two therapeutic options are reviewed: gene transfection and drug therapy. So far, clinical studies have shown that gene transfection cannot effectively restore CFTR function. Simultaneously, several drugs including genistein, phenylimidazothiazoles and gentamicin have been found to activate mutant CFTR, thus, being suitable for single or combined (with gene transfection) treatment.

Genetic patterning of embryonic inner ear development.

The commitment of the otocyst to form balance (pars superior) and hearing (pars inferior) receptors is under the control of patterning genes. Intersecting patterns of gene expression has been proposed to explain the regionalization of inner ear sensory receptor development. Insights into the roles of patterning genes is being acquired from the analysis of inner ear development of null mutation mice. An example of the consequences of the loss of expression of a single patterning gene is the effect of a null mutation of paired-box gene 2 (Pax2) on formation of the cochlea. Pax2 transcripts are expressed in the pars inferior of the otocyst and null mutant inner ears show agenesis of the cochlea. This is an example of the profound effect that loss of a single patterning gene can have on inner ear development. However, more typically there is redundancy of gene action during inner ear development as exemplified by the overlapping pattern of expression of two closely related homeobox-containing genes (i.e. Hmx2 and Hmx3) in the pars superior of the otocyst. Hmx2 and Hmx3 genes are both expressed early in otic development with Hmx3 transcripts present in the placode. However, null mutation of the Hmx3 patterning gene produced only a limited vestibular defect, and did not result in the agenesis of the vestibule. This result suggests that there is redundancy in genes that have similar patterns of regional expression in the otic anlagen.

Effects of a tyrosine phosphatase inhibitor on chloride secretion in human intestinal epithelia.

AIMS: Transcellular chloride transport is the key event underlying epithelial hydration in the intestine. Little is known about the role of protein tyrosine phosphatases in the regulation of basal and stimulated secretion in human intestinal epithelia. The aim of our study was to investigate the effects of the protein tyrosine phosphatase inhibitor sodium orthovanadate on vectorial chloride transport in native human colon. METHODS: An electrophysiological technique was used to measure changes in short-circuit current via a dual voltage/current clamp in native human colon mucosa and in T84 (ATCC) human intestinal cells mounted in modified Ussing chambers. RESULTS: Orthovanadate (1 mM) added to the serosal side of native human colon caused a net rise in short circuit current, reflecting the stimulation of serosal-to-mucosal chloride movement. Epithelial cells responded similarly to the same concentration of the compound. The stimulatory effect of orthovanadate was enhanced by pretreatment with the tyrosine kinase inhibitor genistein, but only when orthovanadate was added to the basolateral chamber. In contrast, the synergistic interaction did not occur when epithelial cells were previously exposed to the cAMP agonist forskolin. CONCLUSIONS: We show that tyrosine phosphatases may be involved in the regulation of epithelial chloride transport, and that orthovanadate stimulates secretion in the human colon.

Trks and p75 genes are differentially expressed in the inner ear of human embryos. What may Trks and p75 null mutant mice suggest on human development?

Recent work has shown the expression of Neurotrophins low (p75) and high affinity (Trk's A, B, and C) receptors in the developing inner ear sensory neurons of chick and mouse. Likewise the biological significance of such receptor expression was demonstrated by using both Trks and Neurotrophins null mutant mice. The present study was conducted to determine the expression of Trks and p75 proteins in the human inner ear throughout development. Hence to assess the potential role of Neurotrophins in the development of auditory and vestibular specific innervation in man. In other words, we intend to address the issue whether or not what null mutant mice for Trks and p75 have revealed on inner ear development may be relevant for human embryos. Fifty-two inner ears and their cochleovestibular ganglions (CVG) from human embryos and fetuses, ranging from 5 to 24 weeks of pregnancy were analyzed. Both Western blot and immunocytochemistry on frozen sections were used as complementary procedures. Quantitative Western blot studies revealed that Trk-B and C immunoreactivity (IR) appeared by embryonic week 5 in CVG neurons, increased at high levels between embryonic weeks 7 and 12, and later on, in 15 week-old specimens and older began to decrease to minimal levels. Trk-A IR was detected at just moderate levels during 5 and 7 weeks reflecting the presence of NGF high affinity receptors only at these earlier developmental ages. The p75 IR was detected at high degrees in the early stage of the 5th week and at abundant levels in all studied inner ears from the 7th to the 24th pregnancy week. These Western blot observations were corroborated by immunocytochemistry on frozen sections, which also revealed a major distribution of both p75 and Trks on neuronal bodies while p75 appears localized on supporting cells. Our findings reveal a tight correlation between p75 and Trks expression throughout human development and specific inner ear developmental events, such as target-dependent neuronal cell death and afferent hair cells innervation. That kind of association of p75 and Trks temporal pattern with distinctive steps in inner ear developmental schedule, is a feature shared between human embryos and other mammals, such as mouse. Based on the present results and considering them together with the reported phenotype of p75 and Trks null mutant mice, we hypothesize that p75 and Trk receptors, as well as, their binding Neurotrophins may be essential in human inner ear development. Accordingly, they may be required molecules for sensory epitheliums innervation and target-dependent neuronal cell death, during embryogenesis and even early postnatal life, in man.