Does the impact of elective temporary clipping on intraoperative rupture really influence neurological outcome after surgery for ruptured anterior circulation aneurysms?—A prospective multivariate study

Background

Elective temporary clipping (ETC) is increasingly used in surgery for aneurysms. This study was to assess whether the impact of ETC on intraoperative aneurysmal rupture (IAR) translates into neurological outcome.

Methods

Patients who underwent surgery for ruptured anterior circulation aneurysms were prospectively studied for various factors related to ETC, IAR and neurological outcome at 3 months. Univariate and multivariate analyses were performed using SPSS20.

Results

Of the total 273 ruptured aneurysm surgeries studied, IAR was observed in only six out of 132 aneurysms (4.5 %) who had ETC, compared with 78 out of 141 (55.3 %) without ETC (p?<?0.001). Aneurysms complicated by IAR had significantly longer clipping time (8.3 min) compared with those without IAR (1.9 min) (p?<?0.001). IAR had significant association with unfavorable outcome (38 % vs. 24 %) (p?=?0.02). Patients with ETC had significantly shorter clipping time (2.9 min) compared with those without ETC (4.8 min) (p?=?0.02). Unfavorable outcome was noted in 30 out of 132 with ETC (23 %), compared with 48 out of 141 without ETC (34 %) (p?=?0.04). This beneficial effect was nonsignificantly greater in younger and good clinical grade patients. While episodes of ETC within clipping time of 20 min did not show significant difference in outcome, repeated rescue clipping (45 % unfavorable outcome, p?=?0.048) and total clipping time of at least 20 min (75 % unfavorable outcome, p?=?0.008) had significant impact on outcome. In multivariate analysis, the use of ETC (p?=?0.027) and total temporary clipping less than 20 min (p?=?0.049) were noted to result in significantly better outcome, independent of other factors.

Conclusions

The use of ETC decreased the occurrence of IAR and the total clipping time, thereby leading to significantly better outcome, independent of other factors. While repeated elective clipping within total clipping time of 20 min did not influence outcome, repeated rescue clipping and total clipping time of at least 20 min had significant impact on outcome.     

“Artifactual fracture-subluxation” of cervical spine in computed tomography screening sans plain radiographs

Background contextComputed tomography (CT) has become the sole modality of screening for cervical injury in polytrauma because of the high sensitivity, speed, and convenience, thereby eliminating the need for plain radiographs.PurposeWe report two cases of misleading artifactual fracture-subluxation of cervical spine in CT, which could have resulted in needless treatment, and describe its characteristics.Study designCase report and review.MethodsTwo patients who were initially diagnosed with fracture-subluxation on screening CT cervical spine were later noted to have motion artifacts and were reviewed.ResultsThe artifactual nature of the supposed fracture-subluxation was unmasked by the soft-tissue findings of obscuration in sagittal reconstruction and duplication in axial images, along with the presence of double bony margins.ConclusionsMotion artifact in cervical CT screening can lead to a misdiagnosis of fracture subluxation. Duplication of soft tissue is highly suggestive of this motion artifact, and an additional single lateral plain radiograph may avert this pitfall.     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

Basic fibroblast growth factor induces TGF-beta release in an isoform and glioma-specific manner

The aim of the current study was to determine whether basic fibroblast growth factor (bFGF), regulates the release of transforming growth factor-beta1 (TGF-beta1) from C6 glioma cells. The results of the study show that bFGF (2, 5 and 10 ng/ml) dose dependently induced the release of TGF-beta1 from C6 glioma cells, with the 10 ng/ml dose inducing a 2- to 3-fold increase of TGF-beta1 levels. This effect was evident as early as 6 h following treatment, with maximal levels observed at 18 h. The effect of bFGF was largely on latent TGF-beta1, and was isoform specific, as bFGF had no effect on TGF-beta2 release. The bFGF effect on TGF-beta1 was also glioma specific, as no such stimulatory effect was observed in rat cortical astrocytes.     

Antagonism of calcium-induced contractions by some non-specific spasmolytics in depolarized smooth muscles

The effects of papaverine MgCl2, cocaine, DNP, KCN and khellin on responses of some rabbit and rat tissues to CaCl2 were studied in vitro in a depolarizing medium. Guinea pig taenia coli preparation was used for comparison. In rabbit tracheal chain and vas deferens and guinea pig taenia coli preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right without affecting the maxima or slopes. In rat tracheal chain and vas deferens preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right. Furthermore all agents (except cocaine in tracheal chain preparations) depressed the maximum responses. The slopes were unaffected in either preparations. The initial competition and subsequent noncompetition observed in certain tissues is discussed in the light of the reported poor capacity of some tissues to retain Ca++ and the absence of releasable firmly bound Ca++ (11).     

The thalamic intergeniculate leaflet modulates photoperiod responsiveness in Siberian hamsters

Siberian hamsters are seasonal breeders that use changes in day length to synchronize their reproductive effort with those times of the year most favorable for successful reproduction. The ability of Siberian hamsters to measure and respond to changes in day length depends upon accurate photoentrainment of the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. Two pathways have been characterized through which entraining stimuli reach the SCN: the retinohypothalamic tract (RHT), which transmits light information from the retinae, and the geniculohypothalamic tract (GHT) from the intergeniculate leaflet of the thalamus (IGL), which is involved in transmitting both photic and nonphotic cues. Ablating the IGL/GHT results in only modest alterations in entrainment to static day lengths and fails to interfere with seasonal responses induced by transfer from static long day to static short day lengths. Because several studies suggest that the IGL may be involved in tracking the time of dusk and dawn, we sought to determine whether an intact IGL is necessary for hamsters to respond to a simulated natural photoperiod (SNP) in which the time of dusk and dawn gradually changes in a pattern approximating the rate of change in day length that occurs during autumn at the latitude this species inhabits in nature. The results indicate that neurochemical lesions of the IGL alter both the pattern of circadian entrainment and photoperiodic responsiveness of Siberian hamsters to an SNP. Both intact and IGL-lesioned hamsters exhibited testicular regression in shortening day lengths, but only IGL-intact hamsters exhibited seasonal pelage molt.     

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.     

Comparative study of beta-adrenoceptor blocking efficacy of two formulations of esmolol in vivo and in vitro.

The objective of the present study was to compare the cardiovascular beta-blocking activity of two different formulations of esmolol. Spontaneously beating guinea-pig isolated atria and the heart rate and blood pressure of anaesthetized cat were employed in the study to compare the beta-blocking efficacy of the two formulations of esmolol using isoprenaline as an agonist. In guinea-pig isolated atria the standard esmolol formulation (Brevibloc) reduced basal atrial rate more significantly than the indigenously formulated esmolol (test formulation). Both the formulations produced similar parallel rightward shift of cumulative concentration response curves of isoprenaline with closely comparable pA2 values. In anaesthetized cats, only indigenous esmolol formulation significantly decreased basal heart rate. Both the formulations did not modify the basal blood pressure and isoprenaline-induced fall in blood pressure, despite significantly blocking isoprenaline-induced tachycardia. It is suggested that both the formulations produced similar degree of beta-1 adrenoceptor blocking activity.