The effects of oxytocin on intracranial pressure

The commonly used vasodilators sodium nitroprusside and nitroglycerine increase the intracranial pressure (ICP). Oxytocin is also a vasodilator although its primary effect is contraction of uterine smooth muscle. We therefore studied the effect of oxytocin on the ICP of cats. Twelve cats were assigned to two equal groups. One group had normal ICP and in the other the ICP was artificially increased by inflating a balloon placed in the extradural space. All of the cats initially received an oxytocin infusion for 15 min. After a period of stabilization, an additional dose of oxytocin was injected as a bolus. Oxytocin administered as an infusion did not change the ICP significantly in any of the cats. Oxytocin administered as a bolus increased the ICP from 27 +/- 4 to 31 +/- 2 mm Hg in the cats with artificially increased ICP. There were no significant changes in the mean blood pressure or heart rate in either group.     

Magnesium sulfate and ritodrine hydrochloride: systemic and uterine hemodynamic effects

Effects of magnesium sulfate and ritodrine hydrochloride on cardiovascular physiologic characteristics were studied in 70 human subjects treated for preterm labor. Systemic and uterine hemodynamic effects were investigated in five pregnant rhesus monkeys. Systolic blood pressure was minimally affected by either agent. Diastolic pressure, while not affected by magnesium sulfate, decreased 26.3% during ritodrine therapy. Maternal and fetal heart rates were minimally affected by magnesium sulfate. Ritodrine increased maternal and fetal heart rates significantly. In the monkeys, magnesium sulfate increased uterine and placental blood flows (by the microsphere technique) but failed to alter cardiac output. Ritodrine produced an increase in cardiac output but decreased perfusion pressure. Placental blood flow decreased by an average of 27.6%. Ritodrine would therefore seem contraindicated with a compromised fetal environment. Magnesium sulfate, by not altering perfusion pressure, may have a beneficial effect on uterine hemodynamics. These specific and distinct differences in cardiovascular and hemodynamic effects should be considered when either magnesium sulfate or ritodrine is selected as a tocolytic agent.     

HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: the benefit of corticosteroids.

OBJECTIVE: The purpose of this study was to determine the effect of corticosteroids on platelet counts and liver functions in women with pregnancies complicated by the HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. STUDY DESIGN: The study group consisted of 93 patients between 24 and 34 weeks' gestation diagnosed with HELLP syndrome. All were given intramuscular injections of either betamethasone or dexamethasone. The 3 most common regimens used were 12 mg of intramuscular betamethasone administered twice 12 hours apart, 12 mg of intramuscular betamethasone administered twice 24 hours apart, and 6 mg of intramuscular dexamethasone administered 4 times 6 hours apart. Precorticosteroid and postcorticosteroid platelet counts and liver function test results were compared. The differences in improvement in hematologic abnormalities among the 3 corticosteroid regimens were also analyzed. RESULTS: The hematologic abnormalities seen in the 93 patients with HELLP syndrome improved after the administration of corticosteroids. The platelet count increased by 23.3 x 10(3)/microL (P <.001). A statistically significant decrease was seen in liver enzyme levels. The alanine aminotransferase decreased by 31.6 IU/L, the aspartate aminotransferase decreased by 52.1 IU/L, and the alkaline phosphatase decreased by 7.6 IU/L. Of the 3 regimens used, 2 doses of 12 mg of intramuscular betamethasone given every 12 hours improved the liver function to the greatest degree. CONCLUSIONS: This study demonstrates that corticosteroids produce a significant improvement in the hematologic abnormalities associated with HELLP syndrome. Two doses of betamethasone given 12 hours apart was the most effective corticosteroid regimen.     

Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis

WNT2B is a member of the Wnt family, a group of signal transduction proteins involved in embryologic development and stem cell renewal and maintenance. We recently reported homozygous nonsense variants in WNT2B in three individuals with severe, neonatal-onset diarrhea, and intestinal failure. Here we present a fourth case, from a separate family, with neonatal diarrhea associated with novel compound heterozygous WNT2B variants. One of the two variants was a frameshift variant (c.423del [p.Phe141fs]), while the other was a missense change (c.722 G > A [p.G241D]) that we predict through homology modeling to be deleterious, disrupting post-translational acylation. This patient presented as a neonate with severe diet-induced (osmotic) diarrhea and growth failure resulting in dependence on parenteral nutrition. Her gastrointestinal histology revealed abnormal cellular architecture particularly in the stomach and colon, including oxyntic atrophy, abnormal distribution of enteroendocrine cells, and a paucity of colonic crypt glands. In addition to her gastrointestinal findings, she had bilateral corneal clouding and atypical genital development later identified as a testicular 46,XX difference/disorder of sexual development. Upon review of the previously reported cases, two others also had anterior segment ocular anomalies though none had atypical genital development. This growing case series suggests that variants in WNT2B are associated with an oculo-intestinal (and possibly gonadal) syndrome, due to the protein’s putative involvement in multiple developmental and stem cell maintenance pathways.Subject terms: Disease genetics, Diarrhoea     

Radiation induced cytochrome c release causes loss of rat colonic fluid absorption by damage to crypts and pericryptal myofibroblasts

BACKGROUND: Therapeutic or accidental exposure to radiation commonly causes gastrointestinal disturbances, including diarrhoea. Rats subjected to whole body ionising radiation at a dose of 8 Gy lose their capacity to absorb fluid via the descending colon after four days. After seven days, fluid absorption recovers to control levels. AIMS: To investigate the effect of ionising radiation on colonic permeability together with its effect on mitochondria dependent apoptotic signals and intercellular adhesion molecules. METHODS: Rats were irradiated with doses of 0-12 Gy. Colonic permeability was measured by accumulation of fluorescein isothiocyanate (FITC) dextran in crypt lumens. Changes in levels of cytochrome c, caspase 3, E and OB cadherin, beta-catenin smooth muscle actin, and collagen IV were assessed using immunocytochemistry with confocal microscopy. RESULTS: Cytosolic cytochrome c increased after 8 Gy (t(1/2) 1.4 (0.6) hours) and peaked at approximately six hours. Caspase 3 increased more slowly, particularly in crypt epithelial cells (t(1/2) 57 (14.5) hours). Pericryptal myofibroblasts disintegrated within 24 hours as was evident from loss of OB cadherin and smooth muscle actin. This coincided with increased crypt permeability to dextran. Intercellular adhesion between crypt luminal cells was not lost until day 4 when both beta-catenin and E-cadherin were minimal. The half maximal dose-response for these effects was in the range 2-4 Gy. Recovery of colonic transport was concurrent with recovery of pericryptal smooth muscle actin and OB cadherin. The pan caspase inhibitor Z-Val-Ala-Asp.fluoromethylketone (1 mg/kg per day) had a small effect in conserving the pericryptal sheath myofibroblasts and sheath permeability but had no systemic therapeutic effects. CONCLUSIONS: These data suggest that radiation damage to the colon may be initiated by mitochondrial events. Loss of crypt fluid absorption and increased permeability coincided with decreased intercellular adhesion between crypt epithelial cells and loss of pericryptal sheath barrier function.     

Cervical cerclage: twenty years' experience.

During a 20-year period, 40 pregnancies were managed in 32 patients with a diagnosis of an incompetent cervix, a ratio of 1:775 deliveries. Diagnosis before development of symptoms produced a 92% fetal salvage, with 68% reaching 36 weeks of gestation. Development of symptoms before cerclage resulted in only a 40% fetal salvage. Fetal salvage was reduced in cases where membranes bulged beyond the cervix, the cervix was more than 3 cm dilated, or the gestational age was greater than 26 weeks at the time of suture placement. No difference was noted between the Shirodkar and McDonald procedures. Major complications included uterine rupture in three patients and acute chorioamnionitis in two. Because of complications, treatment is contraindicated based on history alone or where close follow-up is not available.     

Anaesthetic considerations in patients with mitral valve prolapse

Mitral valve prolapse (MVP), reported as occurring in up to 17% of healthy individuals, is considered to be the commonest cardiac valvular abnormality. Although the anaesthetic course may be uneventful, complications may arise for the first time in the peri-operative period and include life threatening dysrhythmias, mitral regurgitation and infective endocarditis. Anaesthetic management of three of the seven patients with MVP treated at our institution over a 12-month period is discussed and the literature reviewed.     

The management and mortality of patients undergoing hip fracture surgery following recent acute myocardial infarction

Having major elective surgery within 6 months of an Acute Myocardial Infarction carries an increased risk of re-infarction and death. However delaying surgery in patients with proximal femoral neck fractures would most likely lead to complications secondary to prolonged immobilisation and also provide difficulties with regards to nursing care. The aim of this retrospective study was to assess the mortality of hip fracture patients with a recent myocardial infarction that have undergone surgery at our institution. During the period January 2005 to September 2007, twenty-five patients were identified with an Acute Myocardial Infarction around the time of admission but prior to surgical treatment. There were 20 female and 5 male patients with an average age of 88 years (range: 78 to 98). All patients underwent surgery between 1 and 12 days post Acute Myocardial Infarction. We report mortality rates of 28% and 40% at 1 and 6 months respectively, which is much higher than that of the overall proximal femoral neck fracture population. This group of patients can provide a major dilemma to surgeons and anaesthetists alike with respect to the type and timing of surgery. We hope that this data, the largest published series to date, can provide accurate and timely prognostic information to not only clinicians, but also patients and relatives at such a difficult time.