Current intensity‐ and polarity‐specific online and aftereffects of transcranial direct current stimulation: An fMRI study

Transcranial direct current stimulation (tDCS) induces polarity‐ and dose‐dependent neuroplastic aftereffects on cortical excitability and cortical activity, as demonstrated by transcranial magnetic stimulation (TMS) and functional imaging (fMRI) studies. However, lacking systematic comparative studies between stimulation‐induced changes in cortical excitability obtained from TMS, and cortical neurovascular activity obtained from fMRI, prevent the extrapolation of respective physiological and mechanistic bases. We investigated polarity‐ and intensity‐dependent effects of tDCS on cerebral blood flow (CBF) using resting‐state arterial spin labeling (ASL‐MRI), and compared the respective changes to TMS‐induced cortical excitability (amplitudes of motor evoked potentials, MEP) in separate sessions within the same subjects (n = 29). Fifteen minutes of sham, 0.5, 1.0, 1.5, and 2.0‐mA anodal or cathodal tDCS was applied over the left primary motor cortex (M1) in a randomized repeated‐measure design. Time‐course changes were measured before, during and intermittently up to 120‐min after stimulation. ROI analyses indicated linear intensity‐ and polarity‐dependent tDCS after‐effects: all anodal‐M1 intensities increased CBF under the M1 electrode, with 2.0‐mA increasing CBF the greatest (15.3%) compared to sham, while all cathodal‐M1 intensities decreased left M1 CBF from baseline, with 2.0‐mA decreasing the greatest (?9.3%) from sham after 120‐min. The spatial distribution of perfusion changes correlated with the predicted electric field, as simulated with finite element modeling. Moreover, tDCS‐induced excitability changes correlated more strongly with perfusion changes in the left sensorimotor region compared to the targeted hand‐knob region. Our findings reveal lasting tDCS‐induced alterations in cerebral perfusion, which are dose‐dependent with tDCS parameters, but only partially account for excitability changes.     

Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711)

BACKGROUND: Alagebrium (ALT-711) has been shown to improve renal dysfunction in animal models of diabetes. METHODS: To test its effects in diabetic nephropathy (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2), 7-month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db mice for 12 weeks, while a similar number of diabetic and nondiabetic mice were used as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine, skin, and kidney tissue were measured by enzyme-linked immunosorbent assay. The renal morphometric parameters were assessed by electron and light microscopy. RESULTS: By the 3rd week of treatment, the serum CML level decreased by 41%, and the urinary CML concentration increased by 138% from baseline, while the urinary albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels higher (p < 0.05) in treated group A2, A3, and A4 animals compared with groups which received phosphate-buffered saline, with a similar pattern observed in nondiabetic mice. The renal morphological parameters characteristic of DN decreased in treated compared with untreated mice. CONCLUSION: Alagebrium may prevent, delay, and/or reverse established DN in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products.     

Cardiac resynchronization therapy evaluated by myocardial scintigraphy with <Superscript>99m</Superscript>Tc-MIBI: changes in left ventricular uptake,dyssynchrony, and function

Purpose   ^99mTc-MIBI gated myocardial scintigraphy (GMS) evaluates myocyte integrity and perfusion, left ventricular (LV) dyssynchrony and function. Cardiac resynchronization therapy (CRT) may improve the clinical symptoms of heart failure (HF), but its benefits for LV function are less pronounced. We assessed whether changes in myocardial ^99mTc-MIBI uptake after CRT are related to improvement in clinical symptoms, LV synchrony and performance, and whether GMS adds information for patient selection for CRT. Methods  A group of 30 patients with severe HF were prospectively studied before and 3 months after CRT. Variables analysed were HF functional class, QRS duration, LV ejection fraction (LVEF) by echocardiography, myocardial ^99mTc-MIBI uptake, LV end-diastolic volume (EDV) and end-systolic volume (ESV), phase analysis LV dyssynchrony indices, and regional motion by GMS. After CRT, patients were divided into two groups according to improvement in LVEF: group 1 (12 patients) with increase in LVEF of 5 or more points, and group 2 (18 patients) without a significant increase. Results  After CRT, both groups showed a significant improvement in HF functional class, reduced QRS width and increased septal wall ^99mTc-MIBI uptake. Only group 1 showed favourable changes in EDV, ESV, LV dyssynchrony indices, and regional motion. Before CRT, EDV, and ESV were lower in group 1 than in group 2. Anterior and inferior wall ^99mTc-MIBI uptakes were higher in group 1 than in group 2 (p<0.05). EDV was the only independent predictor of an increase in LVEF (p=0.01). The optimal EDV cut-off point was 315 ml (sensitivity 89%, specificity 94%). Conclusion  The evaluation of EDV by GMS added information on patient selection for CRT. After CRT, LVEF increase occurred in hearts less dilated and with more normal ^99mTc-MIBI uptake.     

Cotrel-Dubousset instrumentation for the treatment of severe scoliosis

In a multicentric study, 36 cases (40 curves) of severe scoliosis were analysed; 19 were idiopathic and 17 neurological, Cobb angles ranged from 70° to 145°, all had undergone three-rod Cotrel-Dubousset (CD) instrumentation. The correction on the frontal plane achieved more than 50% of the preoperative angle (53.9% for idiopathic curves and 55.6% for neurological ones). On the sagittal plane the pathological shape of the spine was reduced and distinctly ameliorated. In ten patients, the authors successfully applied a technique, alternative to the original one, which was based on the use of two or three screws in the lumbar area, one supplementary pedicle transverse claw on the cranial area and two rods connected by a domino, instead of a single rod (the longer one applied on the concave side). The main complications were: one case of infection, three of vascular compression of the duodenum, one of crank-shaft phenomenon and one laminar hook displacement. The excellent result achieved in both, idiopathic and neurological severe and stiff scoliosis shows the efficacy, reliability and versatility of CD three-rod instrumentation. Received: 28 November 1997 Revised: 9 July 1998 Accepted: 3 August 1998     

Analgesic properties of S100A9 C-terminal domain: a mechanism dependent on calcium channel inhibition

Calcium-binding protein S100A9 and its C-terminus peptide (mS100A9p) are anti-inflammatory and induce antinociception in rodents. We investigated the mechanisms involved in this effect, and whether they depend or not on the anti-inflammatory properties of mS100A9p. In mice, mS100A9p inhibited thermal and mechanical hyperalgesia and allodynia induced by either carrageenan or formalin, without interfering with paw edema. mS100A9p also inhibited myeloperoxidase activity (MPO), a marker of granulocyte infiltration, induced by carrageenan, but increased MPO after formalin intraplantar injection. The in vivo analgesic properties of mS100A9p were independent of opioid receptor activation. Calcium flux into dorsal root ganglia neurons induced by KCl was inhibited by mS100A9p, suggesting that this protein is able to inhibit signaling, in sensory neurons. The inhibitory effects of mS100A9p on primary afferent signaling were neither due to intracellular calcium store inhibition nor to calcium chelating properties. However, mS100A9p was able to inhibit calcium currents carried by transiently expressed N-type, but not L-type calcium channels, as demonstrated both by gene transfection techniques and electrophysiology. These data demonstrate that mS100A9p interferes with mechanisms involved in nociception, hyperalgesia and calcium signaling in sensory neurons, modulating primary afferent nociceptive signal by inhibiting activation of N-type voltage operated calcium channels.     

Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma

BACKGROUND AND PURPOSE: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. METHODS AND MATERIALS: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. RESULTS: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained significant. CONCLUSIONS: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials.     

Concerning the application of phenomenology to caring research

When phenomenology is adopted as a framework for conducting nursing research, confusions sometimes arise because the researchers do not clarify their understanding of phenomenology. One of the biggest confusions is whether to follow philosophical phenomenological guidelines or scientific guidelines. While phenomenology began as a philosophy, it is argued here that the guidelines of scientific practice should be followed when conducting caring research. This article sharpens the distinction between philosophical and scientific phenomenology and demonstrates the confusion that can ensue when philosophical phenomenology is uncritically used as the model for scientific research. It does so by examining the work of Crotty.     

Oculo-cerebro-cutaneous syndrome: description of a new case

A newborn girl is described with the following multiple congenital anomalies: an orbital cyst, cutaneous appendages, focal hypo-aplasia of the skin and multiple cerebral cysts. This case of oculo-cerebro-cutaneous syndrome is compared with four previously published cases.     

γδ lymphocytes in mumps meningitis patients

Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the proportion of lymphocytes which bore the γδ T-cell receptor for antigen was significantly higher in CSF than in autologous and heterologous blood samples. γδ T-cell values in CSF of MM patients were also significantly higher than those calculated in CSF specimens from nine children with non-inflammatory neurological disorders. Whether and how the expanded CSF γδ T-lymphocyte subset, either CD8 ⁺ or double-negative (CD4^-/CD8^-), contributes to the eradication of mumps virus infection from the central nervous system represents a central focus of our ongoing research.     

Immunomodulator structure-activity relationships: contribution of molecular modeling

Molecular modeling used to compare 64 immunostimulant compounds with pyrrolie quinolein or purine nuclei has pointed out that a common spatial structure is found in most of the active compounds. An additional study of immunostimulants (levamisole, muramyldipeptide) or immunosuppressive molecules (rapamycin) was performed. A common pharmacophore was found on every studied compound. It was composed of three neighboring electroattractive atoms and a further fourth atom. The favorable conformation of rapamycin for immunosuppressive action, which is not the more stable conformation, could explain the loss of its activity, or those of related macrolides, when some minor chemical modifications are tested. These findings validate the proposed concept and provide a view of the mechanism of action of most of the immunomodulator compounds for preparing novel compounds