Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

BACKGROUND: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments. OBJECTIVES: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of 'short cervix' and/or physical examination. History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout. MAIN RESULTS: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.

Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats.

KangFuXinYe (KFX), the ethanol extract of the dried whole body of Periplaneta americana, is a well-known important Chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in China. However, its therapeutic effect and mechanism are not yet well understood. Thus, the aim of this study was to investigate the gastro-protective effects of KangFuXinYe (KFX) in indomethacin-induced gastric damage. Rats were randomly divided into six groups as follows: control, treated with indomethacin (35 mg·kg-1), different dosages of KFX (2.57, 5.14 and 10.28 mL·kg-1, respectively) plus indomethacin, and sucralfate (1.71 mL·kg-1) plus indomethacin. After treatment, rat serum, stomach and gastric homogenates were collected for biochemical tests and examination of histopathology firstly. Rat serum was further used for metabolomics analysis to research possible mechanisms. Our results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric mucosa. Meanwhile, its treatment significantly increased cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2) and epidermal growth factor (EGF) levels in rat serum and gastric mucosa. Moreover, KFX decreased cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) levels. Nine metabolites were identified which intensities significantly changed in gastric damage rats, including 5-hydroxyindoleacetic acid, indoxylsulfuric acid, indolelactic acid, 4-hydroxyindole, pantothenic acid, isobutyryl carnitine, 3-methyl-2-oxovaleric acid, sphingosine 1-phosphate, and indometacin. These metabolic deviations came to closer to normal levels after KFX intervention. The results indicate that KFX (10.28 mL·kg-1) exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action (regulating tryptophan metabolism, protecting the mitochondria, and adjusting lipid metabolism, and reducing excessive indomethacin).

Drug therapy in hypoxic-ischemic cerebral insults and intraventricular hemorrhage of the newborn.

Recent progress in understanding the pathophysiology of hypoxic-ischemic encephalopathies and intraventricular hemorrhages have enabled us to propose new therapeutic modalities in preventing the development and severity of these disorders in the newborn. Because neuronal damage may be reversible under certain conditions, appropriate evaluation of these drugs (single or in combination) is very important in the continuous attempt to ameliorate the neurodevelopmental outcome of these infants. An interventionist attitude should prove to be a better alternative than a supportive one.

Anti-ulcer activity of Sandalwood (Santalum album L) stem hydro-alcoholic extract in three gastric-ulceration models of Wistar rats / Actividad anti-ulcerosa del tallo de Sándalo (Santalum album L) en extractos hidro-alcoholicosen tres modelos de ulceración gástrica de ratas Wistar

Sandalwood (Santalum album L.) is used in various traditional systems of medicine, like Ayurveda, Siddha and Unani medicine to treat a wide range of ailments. In Unani medicine, Safed Sandal is used to treat gastric ulcers, hence the present study was undertaken to confirm this claim. A limit test as per OECD guidelines was conducted at a dose of 5000 mg/kg to determine the acute toxic dose of Hydro-alcoholic extract from S. album stem (SASE). Two test doses of SASE (250 and 500 mg/kg) were subjected to screening of anti-ulcer activity by three in-vivo models namely – water immersion - restrain stress, ethanol and indomethacin induced gastric ulceration models in albino wistar rats. A proton-pump inhibitor, Omeprazole 10 mg/kg and H2 receptor antagonist, Ranitidine 50 mg/kg were employed as standard drugs. The results revealed an increase in gastric protection as a significant decrease (p < 0.001) in average number of ulcers, severity of ulcers and cumulative ulcer index was observed in the test groups. Histopathological evidences supported the above findings. The observed anti-ulcer effect of SASE at 500 mg/kg was comparable to that of standard drugs used in the experiments indicating significant anti-ulcer potential especially at higher concentration.

Sándalo (Santalum album L.) se utiliza en diversos sistemas de medicina tradicional, como el Ayurveda, Siddha y Unani para tratar una amplia gama de dolencias. En la medicina Unani, Safed Sandal se usa para tratar úlceras gástricas, por lo tanto, el presente estudio se realizó para confirmar esta afirmación. Una prueba de límite según las directrices de la OCDE se llevó a cabo a una dosis de 5000 mg/kg para determinar la dosis tóxica aguda del extracto hidroalcohólico del tallo de S. álbum (SASE). Dos dosis de prueba de SASE (250 y 500 mg/kg) se sometieron al estudio de la actividad anti-úlcera por tres modelos in vivo, a saber: la inmersión en agua – estrés de restricción, y la ulceración gástrica inducida por etanol e indometacina, en ratas Wistar albinas. Un inhibidor de la bomba de protones, omeprazol 10 mg/kg y el antagonista de los receptores H2, ranitidina 50 mg/kg fueron empleados como fármacos estándar. Los resultados revelaron un aumento de la protección gástrica como una disminución significativa (p < 0.001) en el número promedio de úlceras, la gravedad de las úlceras y el índice de úlcera acumulativo se observó en los grupos de prueba. Evidencias histopatológicas apoyaron las conclusiones anteriores. El efecto anti úlcera observado por efecto de SASE a 500 mg/kg fue comparable a la de fármacos estándar utilizados en los experimentos que indican un significativo potencial anti-úlcera, especialmente a mayores concentraciones.

Comparative trial of rectal indomethacin and cryoanalgesia for control of early postthoracotomy pain.

A randomised double blind trial was carried out over the first two days after thoracotomy to compare the analgesic effects of rectal indomethacin 100 mg administered eight hourly, cryoanalgesia, and a combination of both of these with the effects of conventional intramuscular opiate analgesia. Pain scores were significantly reduced with both rectal indomethacin alone and cryoanalgesia alone; these treatments had an additive effect when used in combination. Pain on movement was significantly increased, and indomethacin was more effective in reducing this than cryoanalgesia. Groups receiving either indomethacin alone or the combination treatment required significantly less opiate on the first day and exhibited improved peak flow values over the first two days. It is concluded that rectal indomethacin, in this dosage, can provide good, safe analgesia after thoracotomy with minimum administrative difficulty. When used as an adjunct to cryoanalgesia it has an additive effect. There are many potential uses for this drug in other branches of surgery.

Effect of indomethacin on pain relief after thoracotomy.

The effect of indomethacin on postoperative pain was studied in 60 adult patients undergoing thoracotomy in a prospective, randomized, double-blind manner. Patients receiving indomethacin required significantly less opioid after operation and had significantly lower pain scores compared with the control group. Pain on movement and on coughing were reduced also. No major adverse effects were encountered.

Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age.

BACKGROUND: Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavioral reactivity in infants receiving neonatal intensive care. OBJECTIVE: To examine relationship of early neonatal factors and previous medication exposure to subsequent biobehavioral reactivity to acute pain of blood collection. DESIGN: Prospective cohort study. Methods. One hundred thirty-six very low birth weight (

Comparison of the effects of pancuronium and vecuronium in canine coronary and renal arteries.

BACKGROUND: Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done to determine the actions and mechanisms of action of pancuronium on coronary and renal arteries other than those as a sympathomimetic agent. METHODS: Helical strips of coronary and renal arteries from mongrel dogs were suspended in oxygenated, warmed Ringer-Locke solution, and changes in the isometric tension were recorded. In some strips, transmural electrical stimulation (5 Hz for 40 s) was applied to activate perivascular adrenergic nerves. RESULTS: Pancuronium (10[-7] to 10[-5] M) caused dose-dependent relaxation in coronary and renal arteries contracted with prostaglandin (PG) F2alpha, whereas no significant response was induced with vecuronium. The relaxation was endothelium independent and abolished by indomethacin or tranylcypromine, a PGI2 synthase inhibitor. Transmural electrical stimulation caused coronary arterial relaxation, which was augmented by pancuronium and vecuronium. Desipramine also increased the response, and additional potentiation of the response was not elicited by pancuronium and vecuronium. In renal arteries, electrical stimulation caused contraction, which was also augmented by pancuronium and vecuronium. With desipramine treatment, these muscle relaxants did not potentiate the response. Endothelium-dependent coronary arterial relaxation caused by bradykinin was not affected by pancuronium. CONCLUSIONS: Pancuronium-induced relaxations in canine coronary and renal arteries appear to be mediated by PGI2 released from subendothelial tissues. Potentiations by pancuronium and vecuronium of the response to adrenergic nerve stimulation are expected to be due to an inhibition of the norepinephrine uptake but not to facilitated release of the amine.

Indometacina: dosis administrada versus dosis indicada / Indomethacin: Indicated versus administered dose

RESUMENIntroducción. El objetivo del trabajo fue investigar laincidencia de enfermedad invasiva por Streptococcuspneumoniae en pacientes hospitalizados y ambulatoriosatendidos en centros de la ciudad deCórdoba, Argentina.Población, material y métodos. Este estudio de incidenciase realizó entre diciembre de 1999 y noviembrede 2002.Se obtuvieron hemocultivos en todos los pacientesde 2 a 23 meses de edad con sospecha de la enfermedad(temperatura axilar 39 ºC, sospecha clínica deneumonía o sospecha clínica de otra enfermedadinvasiva por Streptococcus pneumoniae). A los pacientescon sintomatología respiratoria y temperatura<39 °C, se les realizó radiografía de tórax y a losque presentaban neumonías con condensación, seles realizó hemocultivo.Tanto la información demográfica y patológica comola evolución de la enfermedad se consignaron enuna hoja de toma de datos.Resultados. La incidencia global de enfermedad invasivapor S. pneumoniae fue de 206,8 por 105/año,mayor en los pacientes de 6 a 17 meses. Entre lasformas de presentación de la enfermedad se encontraron:47,5 por ciento (IC 95 por ciento 40,0 menos 55,0) de bacteriemia sinfoco; 45,8 por ciento (IC 95 por ciento 38,4 menos 53,4) de neumonía; 3,9 por ciento(IC 95 por ciento 1,7 menos 8,2) de meningitis y 2,8 por ciento (IC 95 por ciento 1,0 menos 6,7) de abscesos. El serotipo más frecuente fue el 14en el 45,6 por ciento de los aislamientos, seguido del 6B y 1con ambos en el 10,8 por ciento de los casos. Durante lavigilancia se encontró un 68 por ciento de cepas sensibles,26 por ciento con resistencia intermedia y por ciento resistentes apenicilina.Conclusiones. La tasa de incidencia de la enfermedadinvasiva por S. pneumoniae en niños de Córdoba se sitúa en valores elevados en comparación conLatinoamérica y Europa, probablemente reveladapor la pesquisa de la enfermedad, que en este estudio se realizó en pacientes ambulatorios querepresentaron más de la mitad del total de aislamientos.Palabras clave: incidencia, enfermedad invasiva,pesquisa

Actividad corticoide de las pildoras Chuifong Toukuwan y detección de indometacina

Se estudian las historias clínicas de dos pacientes que presentaron rasgos cushingoides cuando tomaban las píldoras "Chuifong Toukuwan", en dos dosis de seis píldoras cada día. Como parte del programa de control de calidad de los productos medicamentosos se llevó a cabo el estudio in-vivo e in-vitro del medicamento. De esa manera se determinó que contenía indometacina y que no contenía esteroides

Prevençäo da hemorragia periventricular-intraventricular do prematuro: um enfoque farmacológico / Prevention of periventricular and intraventricular haemorrhage of the premature: a pharmacological approach

Apesar dos avanços verificados nos últimos anos em terapia neonatal intensiva, as hemorragias do sistema nervoso central ainda se constituem em expressivas causas morbi-mortalidade para os pequenos prematuros com menos de 35 semanas de idade gestacional e peso de nascimento inferior a 1500g. Sua ocorrência nas primeiras horas de vida pós-natal tem motivado sucessivas pesquisas no sentido de encontrar algum agente que, administrado precocemente, possa preveni-las. Discorre-se nesta revisäo sobre o uso de fenobarbital, brometo de pancurônio, etamsilato, vitamina E, indometacina e teofilina na prevençäo das hemorragias do sistema nervoso central, näo identificando nenhum de eficácia inteiramente comprovada