A prediction model for the response to oral labetalol for the treatment of antenatal hypertension.

This prospective observational study aimed to identify at presentation the maternal hemodynamic and demographic variables associated with a therapeutic response to oral labetalol and to use these variables to develop a prediction model to anticipate the response to labetalol monotherapy in women with hypertension. It was set at a maternity unit in a UK teaching hospital. Maternal demographic data from 50 pregnant women, presenting with hypertension between January and August 2013, was collected and blood pressure measured with a device validated for pregnancy and pre-eclampsia. Maternal haemodynamics were assessed with a bioreactance monitor. Participants were commenced on oral labetalol, and reviewed until delivery and discharge home. Logistic regression analysis was performed to assess the prediction of response to labetalol according to the maternal demographic and hemodynamic variables. Main outcome measures were the response to labetalol monotherapy up to delivery and discharge home, defined as sustained blood pressure control <140/90, and the rates of severe hypertension. Thirty-seven women (74%) had their blood pressure well controlled with labetalol monotherapy, 13 (26%) failed to achieve control with labetalol alone, of whom 9 developed severe hypertension. Multivariate logistic regression showed that heart rate, ethnicity and stroke volume index were independent predictors of the response to labetalol. The predictive accuracy of the model was 96% (95% confidence interval (CI) 86-99%). Maternal demographics and haemodynamics are potent predictors for the response to labetalol, and these parameters may guide therapy to enable effective blood pressure control and a lowering of severe hypertension rates.

Longitudinal hemodynamics in acute phase of treatment with labetalol in hypertensive pregnant women to predict need for vasodilatory therapy.

OBJECTIVE: Hypertensive pregnant women who do not respond to treatment with labetalol to control blood pressure (BP), but require vasodilatory therapy, progress rapidly to severe hypertension. This could be delayed by early recognition and individualized treatment. In this study, we sought to create prediction models from data at presentation and at 1 h and 24 h after commencement of treatment to identify patients who will not have a sustained response to labetalol and therefore need vasodilatory therapy. METHODS: The study population comprised 134 women presenting with hypertension at a UK hospital. Treatment with oral labetalol was administered when BP was > 150/100 mmHg or > 140/90 mmHg with systemic disease. BP and hemodynamic parameters were recorded at presentation and at 1 h and 24 h after commencement of treatment. Labetalol doses were titrated to maintain BP around 135/85 mmHg. Women with unresponsive BP, despite labetalol dose maximization (2400 mg/day), received additional vasodilatory therapy with nifedipine. Binary logistic and longitudinal (mixed-model) data analyses were performed to create prediction models anticipating the likelihood of hypertensive women needing vasodilatory therapy. The prediction models were created from data at presentation and at 1 h and 24 h after treatment, to assess the value of central hemodynamics relative to the predictive power of BP, heart rate and demographic variables at these intervals. RESULTS: Twenty-two percent of our cohort required additional vasodilatory therapy antenatally. These women had higher rates of severe hypertension and delivered smaller babies at earlier gestational ages. The unresponsive women were more likely to be of black ethnicity, had higher BP and peripheral vascular resistance (PVR), and lower heart rate and cardiac output (CO) at presentation. Those who needed vasodilatory therapy showed an initial decrease in BP and PVR, which rebounded at 24 h, whereas BP and PVR in those who responded to labetalol showed a sustained decrease at 1 h and 24 h. Stroke volume and CO did not decrease during the acute phase of treatment in either group. The best model for prediction of the need for vasodilators was provided at 24 h by combining ethnicity and longitudinal BP and heart rate changes. The model achieved a detection rate of 100% for a false-positive rate of 20% and an area under the receiver-operating characteristics curve of 0.97. CONCLUSION: Maternal demographics and hemodynamic changes in the acute phase of labetalol monotherapy provide a powerful tool to identify hypertensive pregnant patients who are unlikely to have their BP controlled by this therapy and will consequently need additional vasodilatory therapy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. RESUMEN OBJETIVO: Las embarazadas hipertensas que no responden al tratamiento con labetalol para el control de la presión arterial (PA), pero que requieren terapia vasodilatadora, evolucionan rápidamente hacia una hipertensión severa. Ésta se puede retrasar mediante un diagnóstico precoz y un tratamiento individual. En este estudio se ha tratado de crear modelos de predicción a partir de datos al inicio del tratamiento y al cabo de 1 hora y de 24 horas después del mismo, para identificar a las pacientes que no mostrarán una respuesta constante al labetalol y que por lo tanto necesitarán terapia vasodilatadora. MÉTODOS: La población de estudio incluyó 134 mujeres con hipertensión en un hospital del Reino Unido. El tratamiento con labetalol por vía oral se administró cuando la PA fue >150/100 mm de Hg o >140/90 mm de Hg con enfermedad multisistémica. Se registró la PA y los parámetros hemodinámicos tanto al inicio como al cabo de 1 h y de 24 h después del inicio del tratamiento. Las dosis de Labetalol se ajustaron para mantener la PA en torno a los 135/85 mm de Hg. Las mujeres cuya PA no produjo respuesta, a pesar de haberles administrado la dosis máxima de labetalol (2400 mg/día), recibieron terapia vasodilatadora adicional con nifedipino. Se realizaron análisis de datos mediante logística binaria y longitudinal (modelo mixto), para crear modelos de predicción con los que pronosticar la probabilidad de la necesidad de terapia vasodilatadora en mujeres hipertensas. Los modelos de predicción se crearon a partir de datos al inicio y al cabo de 1 hora y 24 horas del tratamiento, para evaluar el valor de los parámetros hemodinámicos principales con respecto a la capacidad predictiva de la PA, la frecuencia cardíaca y las variables demográficas en estos intervalos. RESULTADOS: El 22 % de la cohorte necesitó terapia vasodilatadora adicional antes del parto. Estas mujeres tuvieron tasas más altas de hipertensión grave y neonatos más pequeños en edades gestacionales más tempranas. Las mujeres que no respondieron al tratamiento fueron con más frecuencia de raza negra, tuvieron la PA y la resistencia vascular periférica (RVP) más alta, y la frecuencia cardíaca y el gasto cardíaco (GC) más bajos al inicio del tratamiento. Aquellas que necesitaron terapia vasodilatadora mostraron un descenso inicial de la PA y la RVP, que se recuperó al cabo de 24 h, mientras que la PA y la RVP en las que respondieron al labetalol mostraron una disminución constante al cabo de 1 h y de 24 h. El volumen sistólico y el GC no disminuyeron durante la fase aguda del tratamiento en ninguno de los grupos. El mejor modelo para la predicción de la necesidad de vasodilatadores se obtuvo a las 24 h mediante la combinación de la etnia con los cambios longitudinales de la PA y la frecuencia cardíaca. El modelo alcanzó una tasa de detección del 100% para una tasa de falsos positivos del 20% y un área bajo la curva de características operativas del receptor de 0,97. CONCLUSIÓN: Los datos demográficos maternos y los cambios hemodinámicos en la fase aguda de la monoterapia con labetalol constituyen una herramienta poderosa para identificar a las pacientes embarazadas hipertensas con pocas probabilidades de que se les pueda controlar su PA mediante esta terapia y que por lo tanto necesitarán terapia vasodilatadora adicional. : 、(blood pressure,BP),。。,1 h24 h,。 : 134。BP>150/100 mmHgBP>140/90 mmHg。1 h24 hBP。,BP135/85 mmHg。BP,()。logistic(),。1 h24 h,,BP、。 : 22%。。,BP(peripheral vascular resistance,PVR),(cardiac output,CO)。BPPVR,24 h,1 h24 hBPPVR。CO。24hBP。100%,20%,0.97。 : ,BP。.

Maternal ethnicity and its impact on the haemodynamic and blood pressure response to labetalol for the treatment of antenatal hypertension.

OBJECTIVE: Blood pressure (BP) control outside pregnancy is associated with a reduction in adverse cardiovascular events, and in pregnancy with improved outcomes. Outside pregnancy, there is evidence ß-blockers are less effective in controlling BP in black populations. However, in pregnancy, labetalol is recommended as a universal first-line treatment, without evidence for the impact of ethnicity on its efficacy. We sought to compare haemodynamic responses to labetalol in black and white pregnant patients. METHODS: This was a prospective observational cohort study in a London teaching hospital. Maternal haemodynamics were assessed in 120 pregnant women treated with labetalol monotherapy. Measurements were taken at presentation, 1 and 24 h after treatment. Participants were monitored regularly until delivery. Statistical analysis was performed by multilevel modelling. RESULTS: Both groups exhibited similar temporal trends in haemodynamic changes over the first 24 h following labetalol. Both showed a reduction in BP and peripheral vascular resistance within 1 h and in heart rate after 24 h. There was no change in cardiac output and stroke volume in either group. BP control (<140/90) was achieved at 1 h in 79.7% of the white and 77% of the black cohort. At 24 h, control was achieved among 83.1% and 63.9%, and up to the immediate intrapartum period control was achieved in 89.8% and 70.4% of white and black patients, respectively. CONCLUSIONS: There is no difference in the acute haemodynamic changes and hypertension can be controlled throughout pregnancy with labetalol monotherapy in excess of 70% pregnant black and white patients.

[Cryopreserved human sperm deposits: usability after decades of storage]. / Kryokonservierte humane Spermadepots. Brauchbarkeit nach jahrzehntelanger Lagerung.

To determine the effect of long-term storage on cryopreserved human sperm, 238 individual samples from 34 cryopreserved sperm deposits that had been collected between 1976 and 1989 were evaluated at regular intervals. The material was from 34 patients, 18 of whom suffered from underlying malignant disease. Every 3 years a sample from each deposit was thawed for microscopic analysis. During the course of the storage period limited to a maximum of 21 years, all ejaculate parameters had deteriorated in comparison to fresh semen. Quantitative motility was the most sensitive parameter with a decrease of ca. 80%. Sperm density decreased hardly at all. The parameters of the criteria investigated did not decrease linearly or proportionally with the storage duration, but rather more directly after the freezing process or within the first 3 years. These changes became increasingly smaller as the storage time lengthened. Almost all of the deposits exhibited adequate quality at all times during storage. Consequently, 21-year permanent frozen storage in liquid nitrogen is safe regarding aspects of spermatology.

[Retrocaval ureter]. / Retrokavaler Harnleiter.

A 13-year-old boy presented to our clinic with a newly found hydronephrosis, which was caused by a retrocaval ureter. Besides this we noticed a glandular hypospadia. After we made sure that the right kidney had a normal function in the ING, we removed the stenosed ureter segment and performed an end-to-end anastomosis. The DJ stent was removed without any complications 5 weeks after the operation.

Structural analysis of G-DNA in solution: A combination of polarized and depolarized dynamic light scattering with hydrodynamic model calculations.

Specific intra- and intermolecular quadruplex conformations of model G-DNA oligonucleotides have been identified from their translational and rotational diffusion coefficients in aqueous solution. The transport properties were determined by polarized and depolarized dynamic light scattering. A comparison with hydrodynamic model calculations provides detailed information about the size and shape of the molecules and allows one to distinguish between alternative intra- and intermolecular association. The potential of this combination of methods to elucidate biomolecular structures in solution, to characterize conformational changes, and follow intermolecular interaction processes due to a response to external stimuli has been discussed.

Effect of chronic theophylline administration on amphotericin B nephrotoxicity in rats.

The effect of chronic theophylline administration on amphotericin B nephrotoxicity was investigated in rats. A 7-day treatment of amphotericin B (5 mg/kg/day i.p.) significantly reduced the glomerular filtration rate (GFR) measured as inuline clearance and creatinine clearance (0.74 +/- 0.29 and 0.16 +/- 0.04 ml/min, respectively) in comparison to vehicle-treated rats (2.04 +/- 0.23 and 1.29 +/- 0.19 ml/min, respectively). The reduced GFR led to evaluations in serum creatinine and BUN concentrations (0.94 +/- 0.09 and 78 +/- 11 mg/dl) in comparison to their own values before treatment (0.45 +/- 0.11 and 19 +/- 3 mg/dl). In addition amphotericin B induced an increase in sodium and a decrease in potassium excretion, the fractional sodium excretion was elevated 50-fold. The methylxanthine, theophylline, had a beneficial effect on the outcome of amphotericin-B-induced renal failure. The inuline clearance was 1.17 +/- 0.04 ml/min, the creatinine clearance 0.43 +/- 0.03 ml/min, the serum creatinine concentration 0.76 +/- 0.05 mg/dl and the BUN concentration 40 +/- 6 mg/dl. Theophylline had no effect on total sodium excretion and potassium excretion. The fractional sodium excretion, however, improved significantly. Theophylline as well as sodium deoxycholate, the detergent of amphotericin B, given alone had no effect on renal hemodynamics measured after 7 days.

Short-term residential psychotherapy: psychotherapy in a nutshell.

Psychotherapy in a psychotherapeutic community often is characterized by absence of time limits and by long duration. In this article an account is given of the adaptions that are necessary when short-term treatment is carried out in such a residential setting. Implications for focus, therapy program, and treatment style are presented.