Effect of low dose phenylephrine infusion on shivering and hypothermia in patients undergoing cesarean section under spinal anesthesia: a randomized clinical trial.

BACKGROUND: Shivering is a common complication of spinal anesthesia. Phenylephrine, due to its peripheral vasoconstrictive effect, may limit the core to periphery redistribution of body temperature following spinal anesthesia, and reduce hypothermia and shivering. We hypothesized that prophylactic phenylephrine infusion would reduce shivering and hypothermia in women undergoing cesarean section under spinal anesthesia. METHODS: A two-arm randomized, double-blind, placebo-controlled trial in term pregnant patients undergoing cesarean section. In the phenylephrine group (n=75) prophylactic phenylephrine infusion was administered at 25 µg/min immediately after initiation of spinal anesthesia and continued until the end of the operative period. In the placebo group (n=75) a normal saline infusion was administered during the same period. The primary outcome was the incidence of shivering; secondary outcomes were severity of shivering, changes in nasopharyngeal (core) temperature, and incidence of hypotension and bradycardia. RESULTS: The incidence of shivering in the phenylephrine and control groups was 24.0% (95% CI 14.3% to 33.7%) and 53.3% (95% CI 42.0% to 64.6%), respectively. The severity of shivering was greater in the control group (P=0.002) and the mean (±SD) end of surgery core temperature was significantly higher in the phenylephrine group (35.84°C ±â€¯0.60) compared with controls (35.61°C ±â€¯0.48) (P=0.009). The incidence of hypotension was higher in controls (53.4% vs. 2.7%; P <0.001) but bradycardia more frequent in group P (P=0.023). CONCLUSION: The incidence of shivering and degree of hypothermia were significantly reduced by a prophylactic phenylephrine infusion during cesarean section under spinal anesthesia.

A micro-patterned silicon chip as sample holder for macromolecular crystallography experiments with minimal background scattering.

At low emittance synchrotron sources it has become possible to perform structure determinations from the measurement of multiple microcrystals which were previously considered too small for diffraction experiments. Conventional mounting techniques do not fulfill the requirements of these new experiments. They significantly contribute to background scattering and it is difficult to locate the crystals, making them incompatible with automated serial crystallography. We have developed a micro-fabricated sample holder from single crystalline silicon with micropores, which carries up to thousands of crystals and significantly reduces the background scattering level. For loading, the suspended microcrystals are pipetted onto the chip and excess mother liquor is subsequently soaked off through the micropores. Crystals larger than the pore size are retained and arrange themselves according to the micropore pattern. Using our chip we were able to collect 1.5 Å high resolution diffraction data from protein microcrystals with sizes of 4 micrometers and smaller.

Optical coherence tomography changes before the development of choroidal neovascularization in second eyes of patients with bilateral wet macular degeneration.

AIM: To describe the frequency of neovascular age-related macular degeneration (nAMD) in second eyes of patients undergoing ranibizumab therapy in their first eye and to evaluate the patterns of optical coherence tomography (OCT) abnormalities in fellow eyes before nAMD. METHOD: Patients who developed choroidal neovascularization (CNV) in the second eye while on treatment for the first eye were identified. OCT scans of the second eyes, performed before the onset of CNV, were retrospectively examined and graded. Frequency of second eye involvement was estimated and patterns of progression of OCT abnormalities were described and classified. RESULTS: In all, 65 out of 749 consecutive patients required ranibizumab in their second eye for treatment-naïve nAMD over a 2-year period. The mean interval from commencement of ranibizumab in first eye to conversion in second eye was 12 months (2-35.5 months). There were three patterns of CNV development: group A (12%, n=8) had no OCT abnormalities in the second eye just before developing CNV; group B (38%, n=25) had no abnormalities at baseline but developed OCT changes more than one visit before conversion and group C (50%, n=32) had OCT changes from baseline, which did not progress until just before conversion. CONCLUSION: Patients with retinal pigment epithelial elevation without sub-retinal fluid on OCT in their fellow eyes have a high risk of progression to require therapy within a 2-year period. An anticipatory approach may be warranted, but a small group with completely normal OCT appearances can still develop lesions between visits.

Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases.

Kinases of the MARK/Par-1 family of S/T protein kinases are regulators of diverse cellular processes in Caenorhabditis elegans, Drosophila, yeast, and mammalian cells. They are involved in nematode embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARK phosphorylates microtubule-associated proteins such as tau and is a key regulator of microtubule-based intracellular transport. Hyperphosphorylation of tau causes defects in neuronal transport and may induce abnormal aggregation of tau in Alzheimer disease and other tauopathies. Recent high-resolution structure analysis of MARK fragments covering the kinase domain and accessory regulatory domains has revealed important details regarding the autoregulation of MARK, but their interpretation has remained controversial. Here we focus on the structural aspects of MARK activity and autoregulation. Comparison of the available MARK structures with related kinases of the AMPK family and with new structures of MARK isoforms (MARK2 and 3) reveals unexpected structural similarities between these kinases that may help to resolve the existing controversies.

Milk protein polymorphism in Kangayam cattle.

This paper reports the milk protein polymorphism, the allele frequencies of variants and the possible linkages among various combinations of milk protein phenotypes in the Kangayam cattle of south India. Milk samples from 156 Kangayam cows were typed by starch gel and polyacrylamide gel electrophoresis for caseins and whey proteins, respectively. All the four milk protein components studied, alpha(s)1-casein. beta-casein, beta-lactoglobulin and alpha-lactalbumin, exhibited polymorphism with high allele frequencies of 0.9231 +/- 0.0151 for alpha(s)1-casein C, 0.9263 +/- 0.0148 for beta-casein A, 0.9135 +/- 0.0159 for beta-lactoglobulin B and a relatively high frequency of 0.6218 +/- 0.0275 for alpha-lactalbumin A. The mean heterozygosity estimated over all the four milk protein loci was 0.2420. Genetic equilibrium was observed among all the loci studied, except alpha-lactalbumin. Linkage analysis confirmed the non-independence between alpha(s)1- and beta-caseins and between caseins and alpha-lactalbumin phenotypes.

Analysis of risk factors for over-anticoagulation in patients receiving long-term warfarin.

A cohort of patients with an INR >7.0 were identified prospectively and compared with a group of patients with stable anticoagulant control. During the study 15,100 INR measurements were recorded and 31 (0.2%) were >7.0. Odds ratios of patient characteristics were calculated as an estimate of relative risk for the development of a high INR. The highest risk factor was a target INR of 3.5 (OR 7.3, 95% CI 2.6-20.2). The second highest risk factor was antibiotic therapy in the 4 weeks preceding the high INR (OR 6.2, 95% CI 1.4-27.7). Bleeding was reported more frequently in the high INR group (OR 5.4, 95% CI 2.1-13.9). Five major bleeds occurred in this group compared to none in the stable group. This analysis identifies risk factors for over-anticoagulation and hence when to intensify monitoring and when to consider pre-emptive warfarin dose reductions.

Pycnodysostosis with visceral manifestation and rickets.

Pycnodysostosis is a rare bone disease. Visceral manifestations associated with anemia and/or rickets have been reported in pycnodysostosis. Five children with typical findings of pycnodysostosis with hepatosplenomegaly, anemia with rickets, one with visceromegaly and anemia, and another with rickets alone are reported here. These findings strongly suggest that extramedullary erythropoiesis does occur in pycnodysostosis.