Evaluación del proceso de atención urológica de pacientes pediátricos con mielomeningocele / Evaluation of the urological care process of pediatric patients with myelomeningocele

Introducción: El mielomeningocele (MMC) es una de las malformaciones congénitas más severas compatible con la vida. El 90% de los pacientes presenta vejiga neurogénica que debe ser evaluada y tratada precozmente. Objetivos: Describir la evaluación y tratamiento nefrourológico recibido por pacientes con MMC hasta el momento de la primera consulta en el Hospital Garrahan (periodo pre-ingreso). Describir la evaluación realizada y el tratamiento urológico implementado a partir del ingreso al hospital Garrahan (periodo post-ingreso). Evaluar la prevalencia de Enfermedad Renal Crónica (ERC). Población y Métodos: Se realizó un estudio con diseño clínico analítico, retrospectivo, longitudinal sobre pacientes con MMC de 1 mes a 18 años derivados al Hospital Garrahan para atención ambulatoria en los años 2011 y 2012. Resultados: Se incluyeron115 pacientes. Al momento de la derivación al hospital ("pre-ingreso") 7% de los pacientes habían logrado completar evaluación nefrourológica, (ecografía vesicorenal, urodinamia, Cistouretrografía, Centellograma renal y Creatininemia). Tratamiento: 33% vaciaban vejiga por CIL o vesicostomía y 21% recibían Oxibutinina. A partir del ingreso al seguimiento en el Garrahan 83% lograron completar la evaluación, y en función del resultado de la misma se indicó CIL en 87% y Oxibutinina en el 66% de los pacientes. La prevalencia de ERC al ingreso fue de 43%; la mayoría en estadio I. Conclusiones: La mayoría de los pacientes con MMC fueron derivados al hospital de tercer nivel con evaluaciones urológicas incompletas y sin el tratamiento adecuado de la vejiga neurogénica. El inicio del seguimiento interdisciplinario en un hospital de alta complejidad facilitó la realización de las evaluaciones necesarias y la implementación del tratamiento adecuado (AU)

Introduction: Myelomeningocele (MMC) is one of the most severe congenital malformations compatible with life. Of all the patients, 90% presents with a neurogenic bladder requiring early evaluation and treatment. Objectives: To describe the uronephrological evaluation and treatment received by patients with MMC up to the first consultation at Garrahan Hospital (pre-follow-up period). To describe the urological evaluation and treatment implemented from referral to Garrahan Hospital (follow-up period). To evaluate the prevalence of chronic kidney disease (CKD). Population and Methods: A retrospective, longitudinal study with a clinical, analytical design was conducted in patients with MMC between 1 months and 18 years of age referred to Garrahan Hospital for outpatient care in 2011 and 2012. Results: 115 patients were included. At the time of referral to the hospital ("pre-follow-up") 7% of the patients had undergone complete uronephrological evaluation (kidney-bladder ultrasonography, urodynamic studies, cystourethrography, renal scintigraphy, and creatininemia levels). Treatment: 33% emptied their bladder by CIC or vesicostomy and 21% received oxybutynin. From follow-up initiation at Garrahan Hospital, 83% underwent complete evaluation, and based on the results CIC was indicated in 87% and oxybutynin in 66% of the patients. On admission, prevalence of CKD was 43%; with stage I in the majority of the patients. Conclusions: The majority of the patients with MMC were referred to a third-level hospital with incomplete urological studies and without adequate treatment of the neurogenic bladder. Initiation of interdisciplinary follow-up at a tertiary hospital allowed for the necessary studies and implementation of adequate treatment (AU)

Hyperactive EGF receptor, Jaks and Stat3 signaling promote enhanced colony-forming ability, motility and migration of cisplatin-resistant ovarian cancer cells.

We present evidence that the cisplatin-resistant human ovarian cancer lines, A2780S/CP1 (S/CP1), A2780S/CP3 (S/CP3) and A2780S/CP5 (S/CP5), derived by subjecting the sensitive A2780S ovarian cancer line to multiple rounds of cisplatin treatments followed by recovery and are resistant to 1, 3 and 5 µM cisplatin, respectively, have increased colony-forming ability and altered morphology that is consistent with enhanced motility, migration and invasiveness in vitro. The malignant phenotype progresses with increasing resistance and is associated with hyperactive epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (Erk)1/2 and janus kinases (Jaks), aberrant signal transducer and activator of transcription (Stat) 3 activation promoted by EGFR and Jaks, and epithelial-mesenchymal transition (EMT) in vitro. Survivin and FLIP anti-apoptotic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase activities are also elevated in the resistant cells. Accordingly, the ectopic expression of constitutively-active Stat3C in the sensitive A2780S cells diminished cisplatin sensitivity. The inhibition of EGFR or Stat3 activity repressed Survivin, VEGF and Vimentin expression and the colony-forming potential, viability, motility and migration of the resistant cells, and sensitized them to cisplatin. Analysis of human ovarian cancer patients' tumor tissues shows aberrantly-active EGFR and Stat3 that in certain cases correlate with Vimentin over-expression. Intra-peritoneal mouse xenograft studies revealed, compared with the sensitive A2780S line that had low tumor incidence restricted to the ovary, a high tumor incidence for the resistant S/CP3 and S/CP5 lines that formed tumor nodules at several locations on the small intestine and colon, and which responded poorly to cisplatin, but were sensitive to concurrent treatment with cisplatin and EGFR or Stat3 inhibitor. Hyperactive EGFR signaling through Stat3 and the Jak-Stat3 activity together promote ovarian cancer progression to cisplatin resistance and therefore represent targets for preventing the development of cisplatin resistance and the recurrent disease during cisplatin therapy in ovarian cancer.

Micro-structured fiber Bragg gratings: optimization of the fabrication process.

This work has been devoted to present and demonstrate a novel approach for the fabrication of micro-structured fiber Bragg gratings (MSFBGs) with enhanced control of the geometric features and thus of the spectral properties of the final device. The investigated structure relies on the localized stripping of the cladding layer in a well defined region in the middle of the grating structure leading to the formation of a defect state in the spectral response. In order to fully explore the versatility of MSFBGs for sensing and communications applications, a technological assessment of the fabrication process aimed to provide high control of the geometrical features is required. To this aim, here, we demonstrate that the optimization of this device is possible by adopting a fabrication process based on polymeric coatings patterned by high resolution UV laser micromachining tools. The function of the polymeric coating is to act as mask for the HF based chemical etching process responsible for the cladding stripping. Whereas, UV laser micromachining provides a valuable method to accurately pattern the polymeric coating and thus obtain a selective stripping along the grating structure. Here, we experimentally demonstrate the potentiality of the proposed approach to realize reliable and cost efficient MSFBGs enabling the prototyping of advanced photonics devices based on this technology.

Respiratory effects on systolic time intervals during pericardial effusion.

Pericardial effusion without cardiac tamponade is defined by the detection of excessive pericardial fluid without clinical manifestations, particularly pulsus paradoxus (inspiratory decrease in systolic blood pressure greater than 10 mm Hg) and jugular venous distention. Nineteen consecutive patients without heart or lung disease who had pericardial findings and no evidence of tamponade were investigated by echocardiography: 14 with pericardial effusion and 5 with noneffusive ("dry") pericarditis. Patients with effusion had an inspiratory decrease in left ventricular ejection time (delta LVET) of 17.9 +/- 5.78 ms and an increase in preejection period (delta PEP) of 12.1 +/- 3.78 ms, each well beyond the respective respiratory changes measured in normal subjects. The 5 control patients with dry pericarditis had a mean delta LVET and delta PEP of only 8.0 and 7.0 ms, respectively. Of the 14 patients with effusion, 6 whose systolic pressure showed no respiratory change had mean delta LVET of 13.7 ms and delta PEP of 11.2 ms, comparable to the other 8 patients with effusion who had a respiratory change of 2 to 10 mm Hg. We conclude that although pulsus paradoxus was not present, excessive pericardial fluid is not physiologically inert. If a satisfactory echocardiogram is not available, exaggerated respiratory fluctuation in systolic time intervals may be evidence of excessive pericardial fluid.

Exaggerated respiratory variation in left ventricular ejection time during lax pericardial effusion.

In 20 consecutive patients with echocardiographic pericardial effusions and no pulsus paradoxus or other signs of cardiac embarrassment the left ventricular ejection time fell (delta LVET) during inspiration by 18.3 +/- 2.47 (SE) ms, greatly exceeding mean inspiratory delta LVET in normal subjects (7.0 ms). Median and mode delta LVET were each 15.0 ms, with delta LVET less than 10 ms and more than 25 ms in only 1 patient each. With a single exception, the magnitude of the abnormal delta LVET was least in patients with minimal to small effusions. Ejection time indices were normal during expiration and low during inspiration, indicating diminished stroke volume during inspiration only. Thus, even without clinical and echocardiographic signs of cardiac compression, the presence of pericardial fluid clearly exaggerated respiratory effects on left ventricular function but not to the degree characteristic of overtly compressing (tamponading) fluid. The consistent exaggeration of delta LVET during even small pericardial effusions is thus of physiologic interest and may be of diagnostic value.

Rate of rise of the carotid pulse. An investigation of observer error in a common clinical measurement.

Bedside estimation of the rate of rise of the carotid pulse is a standard clinical observation whose reliability has not been determined. To ascertain interobserver agreement (primary objective) and compare the velocity of rise of the carotid displacement (not pressure) pulse (supplementary objective), three blinded observers evaluated, ranked and palpated the velocity of rise of carotid pulse as "unremarkable," "slow" or "rapid" in 20 consecutive patients. The relative rate of rise of the recorded carotid pulse was represented by the angle between baseline and the initial carotid peak at a standard paper speed of 100 mm/s. Chi-square analyses yielded no significant interobserver agreements (probability [p] 0.22 to 0.51). There was also no correlation of observers' ranking of rise of carotid pulse with the ranking from independent measurement of the recorded pulse rise velocity (p = 0.10 to 0.99). Observer agreement was unanimous only four times and even in these instances was consistent with the recorded carotid pulse rise velocity only once. The results suggest that unbiased observers cannot reliably discriminate slow from "normal" velocity of rise of carotid pulse.

Responses of peak ear-pulse derivative to changing left ventricular function.

The ear densitograph displacement pulse derivative (dD/dtear) is the analog of the arterial pressure derivative (dP/dt) and behaves comparably under a variety of cardiocirculatory challenges. Technical reliability and uniform application of the transducer are advantages that make it ideal for intrasubject monitoring. With atrial fibrillation as a model of functional variability in eight subjects, peak dD/dtear (P) tracked echocardiographic stroke volume, ejection fraction, ejection rate, and velocity of circumferential fiber shortening quite closely with the exception of some values in three subjects, two of whom had mitral regurgitation and one paradoxic septal movement. In all subjects, P showed good to excellent correlations with cycle length, preejection period (PEP), LVET (left ventricular ejection time), and PEP/LVET. The method appears to be ideally suited to intrasubject monitoring for changing ventricular function.

Strategy for determining local area need for cardiovascular surgical services.

At the request of the Connecticut State Council on Hospitals, a study was made of existing and needed facilities for cardiovascular surgery in the Hartford area. Adequate data on incidence or prevalence of cardiovascular disease were unavailable, and agreed-upon criteria for selecting suitable candidates for surgical intervention were lacking. It was therefore impossible to estimate need for cardiovascular surgery as a basis for determining the need for additional facilities. Instead, estimates were made of potential caseloads, based on trends in rates of cardiac surgery nationwide for 1961-69 and on actual rates in the Hartford area hospitals in 1972. These estimates of potential caseloads were compared with the capacity of existing surgical units as determined by onsite surveys of surgical units, diagnostic facilities, and supportive services and personnel. The methods described provided evidence to suggest that expansion of cardiac surgical services in the Hartford area would be inappropriate. Of more practical import, the approach, although not unassailable, affords one mechanism for focusing discussion of need for facilities on questions of "probable use" of services, rather than on vague generalities based on unknown and immeasurable "needs" for cardiac surgery.