Enhanced H-reflex with resistance training is related to increased rate of force development

Parallel increases in strength and rate of force development (RFD) are well-known outcomes from the initial phase of resistance training. However, it is unknown whether neural adaptations with training contribute to improvements of both factors. The aim of this study was to examine whether changes in H-reflex amplitude with resistance training can explain the gain in strength or rather be associated with RFD. Twelve subjects carried out 3 weeks of isometric maximal plantarflexion training, whereas 12 subjects functioned as contr ols. H-reflexes were elicited in the soleus muscle during rest and sub-maximal contractions at 20 and 60% of maximal voluntary contraction (MVC). In addition, surface electromyography (sEMG) was recorded from the soleus, gastrocnemius and tibialis anterior muscles during MVC. The resistance training provided increases in maximal force of 18%, RFD of 28% and H-reflex amplitude during voluntary contractions of 17 and 15% while no changes occurred in the control group. In contrast, the maximal M-wave, the maximal H-reflex to maximal M-wave ratio during rest and sEMG during MVC did not change with training. There was a positive correlation between percentage changes in H-reflex amplitude and RFD with training (r = 0.59), while significant association between percentage changes in H-reflex amplitude and maximal force was not found. These findings indicate the occurrence of changed motoneuron excitability or presynaptic inhibition during the initial phase of resistance training. This is the first study to document that increased RFD with resistance training is associated with changes in reflex excitability.     

Symptom profiles and palliative care in advanced pancreatic cancer—a prospective study

Objectives To describe prospectively the prevalence and severity of disease-related symptoms, quality of life (QOL) and need for palliative care in patients with advanced pancreatic cancer.Patients and methods Fifty-one patients treated for advanced pancreatic cancer filled in the Edmonton Symptom Assessment Scale (ESAS) for symptom registration and the EORTC QLQ-C30 and QLQ-PAN26 quality of life questionnaires at first contact (baseline) and the ESAS in the following consultations. Need for palliative interventions were registered.Results Of the 22 women and 29 men (mean age, 62 years), 20 had locally unresectable cancer, 19 had metastatic disease, and 12 had recurrent disease after curative resection. Forty-six patients died during follow-up (median survival, 99 days). At baseline, patients reported significantly impaired QOL on nine of 15 scales/items (p<0.01) relative to the general population. Fatigue, loss of appetite, and impaired sense of well-being were the most troublesome symptoms on the ESAS, measured to 4.4(±2.8)/5.3(±2.3), 4.4(±3.2)/5.9(±2.7), and 4.0(±2.9)/4.6(±2.7) (mean±SD) at baseline and 8 weeks before death, respectively. Forty-four of the 51 (86%) initial consultations and 107 (58%) of the 185 follow-ups (124 clinical and 61 phone-calls) resulted in palliative care interventions, most frequently changes in opioid or laxative medication and dietary advice.Conclusions Patients with advanced pancreatic cancer develop several distressing symptoms. ESAS was useful for assessment of symptom prevalence and intensity and is a clinically adequate method for symptom control. A multidisciplinary approach is necessary for the best palliation of symptoms at the time of diagnosis and during follow-up.     

Short-lasting, Unilateral, Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT Syndrome): IV. Respiratory sinus arrhythmia during and outside paroxysms

SUNCT is a headache syndrome characterized by short-lasting (usually 15-120 sec), unilateral head pain paroxysms localized in the peri-ocular area, accompanied by conjunctival injection, lacrimation, nasal stuffiness, rhinorrhea, and subclinical forehead sweating, all on the symptomatic side. A relative bradycardia seems to be an integral part of the paroxysm; a parasympathetic stimulation could theoretically be the causative factor for the bradycardia. In 3 SUNCT patients, vagal nerve function (E:I ratio) has been monitored outside and during pain paroxysms, while 3 other patients could be studied in the attack-free period only. E:I ratio is obtainable in the course of a maximally deep breath and represents the ratio of the longest R-R interval during a 5 sec long expiration to the shortest R-R interval during a 5 sec long expiration. The mean E:I ratio of SUNCT patients outside paroxysms was significantly higher than the mean E:I ratio in an aged-matched control group. The E:I ratio was, however, significantly decreased during paroxysms in comparison with ratios obtained outside the pain paroxysms. After 0.6 mg atropine administration s.c. to one of the patients in the symptomatic phase, the heart rate increased, and the relative bradycardia during headache paroxysm was diminished (but not completely abolished). The E:I ratio was lowered but it was still slightly larger outside than during attacks. The reason for the abrupt and seemingly clear attack-related decrement in E:I ratio together with the previously described relative bradycardia remains enigmatic, however the possibility of increased parasympathetic tone cannot be excluded.     

Left ventricular opacification after intravenous injection of albunex? The effect of different administration procedures

A clinical study has been performed to investigate the influence of different administration procedures on the degree of contrast enhancement of the left ventricle. The administration variables assessed included Albunex^® injection rate, arm position, flushing rate and flushing fluid. Twenty-four healthy male volunteers were included. Compared to an injection rate of 1 ml/sec an injection rate of Albunex^® of 2 ml/sec caused an earlier appearance of contrast in the right ventricle (1 heart beat), whereas transpulmonary passage was not influenced. Horizontal arm position caused a delay in time to peak intensity of 2 to 3 heart beats in both systole and diastole as compared to elevated arm position. Injection rate of 1 ml/sec compared to 2 ml/sec caused a higher peak intensity and mean area under the curve and a longer mean time to peak intensity and transit time. Differences varied from 6 to 230 grey level units out of mean values of 2500. All the observed differences were small and thus probably of no clinical importance.The present study indicates that improvements in the pressure stability characteristics of the albumin microspheres in Albunex^® have been achieved. This implies that a simple administration procedure can be used. It is recommended that the contrast agent, after resuspension, is injected through a three-way stop cock cannula, followed by 10 ml of saline for flushing. The cannulas or syringes used should be no smaller than 20 G. The injection rate should be 1–2 ml/sec, depending on the diameter of the cannula. By using this procedure, a reliable transpulmonary passage and left ventricular opacification may be obtained.     

New-onset posttransplantation diabetes mellitus: insulin resistance or insulinopenia? Impact of immunosuppressive drugs, cytomegalovirus and hepatitis C virus infection

Restoration of renal function may ameliorate uremia induced insulin resistance. Therefore it seems a paradox that new-onset posttransplantation diabetes mellitus (PTDM) is a frequently observed complication after renal transplantation. The incidence varies between 2 and 50% depending on the population under study, criteria for the diagnosis of diabetes and the time of follow up. This review addresses recent findings on transplant specific risk factors and pathogenesis of PTDM after solid organ transplantation, and we focus on the following issues: 1. The relative impact of insulin resistance and insulinopenia in the pathogenesis of PTDM. 2. The role of immunosuppressive drugs with special emphasis on calcineurin inhibitors (cyclosporine A, tacrolimus) and steroids. 3. The possible roles of cytomegalovirus and hepatitis C infections. CONCLUSIONS: New-onset PTDM is characterized by a variety of clinical manifestations, ranging from predominantly insulin resistance which can be handled with lifestyle intervention, to beta-cell failure requiring insulin treatment. The etiology is multi-factorial, but diabetogenic immunosuppressive drugs are of major importance. Future studies should therefore address the effects of different immunosuppressive regimens on the incidence of PTDM. In addition, the impact of cytomegalovirus infection and hepatitis C on PTDM needs further evaluation.     

Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells

Epithelial to mesenchymal transition (EMT) induces cell plasticity and promotes metastasis. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) and the pleiotropic cytokine interleukin 6 (IL-6) have both been implicated in tumor cell metastasis and EMT, but via distinct pathways. Here, we show that direct interplay between YB-1 and IL-6 regulates breast cancer metastasis. Overexpression of YB-1 in breast cancer cell lines induced IL-6 production while stimulation with IL-6 increased YB-1 expression and YB-1 phosphorylation. Either approach was sufficient to induce EMT features, including increased cell migration and invasion. Silencing of YB-1 partially reverted the EMT and blocked the effect of IL-6 while inhibition of IL-6 signaling blocked the phenotype induced by YB-1 overexpression, demonstrating a clear YB-1/IL-6 interdependence. Our findings describe a novel signaling network in which YB-1 regulates IL-6, and vice versa, creating a positive feed-forward loop driving EMT-like metastatic features during breast cancer progression. Identification of signaling partners or pathways underlying this co-dependence may uncover novel therapeutic opportunities.     

Spontaneous hemorrhagic Descemet membrane detachment causing pupillary block

Purpose. To present a unique case of a 65-year-old man using warfarin who presented with acute unilateral loss of vision due to hemorrhagic Descemet membrane detachment (DMD) with pupillary block and elevated intraocular pressure and its subsequent treatment and challenges. Method. Case report. Results. Clinical examination showed a visual acuity of finger counting, central DMD with near contact to the iris and premembrane hemorrhage, an intraocular pressure (IOP) of 19 mmHg, and normal pupillary reaction. An International Normalized Ratio (INR) of 4.9 was treated with dose reduction and vitamin K. Twelve hours later the patient re-presented with an acute increase in pain and an IOP of 78 mmHg with pupillary block and iris bombé. YAG-laser membranotomy, anterior chamber paracentesis, and maximal topical and systemic therapy were unsuccessful in reducing the IOP. Surgical management, including irrigation and aspiration of blood, led to a normalization of the IOP. Descemet stripping automated endothelial keratoplasty (DSAEK) resulted in a visual acuity of 0.3. Deep stromal/pre-Descemet membrane neovascularization was found bilaterally, suspicious for a previous interstitial keratitis. Conclusions. The previously unreported complication of pupillary block following a pre-Descemet membrane hemorrhage was treated successfully for the first reported time, in a 2-step DSAEK. This indicates that DSAEK could be considered as a treatment option for DMD, especially in traumatic circumstances.     

Widespread Hyperalgesia in Adolescents With Symptoms of Irritable Bowel Syndrome: Results From a Large Population-Based Study

Widespread hyperalgesia is well documented among adult patients with irritable bowel syndrome (IBS), but little is known about pain sensitivity among adolescents with IBS. We examined pain sensitivity in 961 adolescents from the general population (mean age 16.1 years), including pain threshold and tolerance measurements of heat (forearm) and pressure pain (fingernail and shoulder) and cold pressor tolerance (hand). Adolescents with IBS symptoms (Rome III criteria) had lower heat pain thresholds compared to controls after adjustments for sex, comorbid pain, and psychological distress (mean difference = –.8°C; 95% confidence interval [CI] = ?1.6 to ?.04). Similar results were found for pressure pain threshold at the shoulder (mean difference = ?46 kPa; 95% CI = ?78 to ?13) and fingernail (mean difference = –62 kPa; 95% CI = ?109 to ?15), and for an aggregate of all 3 threshold measures (z-score difference = ?.4; 95% CI = ?.6 to ?.2), though pressure pain threshold differences were nonsignificant after the final adjustments for psychological distress. No difference of pain tolerance was found between the IBS cases and controls. Our results indicate that adolescents in the general population with IBS symptoms, like adults, have widespread hyperalgesia.PerspectiveThis is the first report of widespread hyperalgesia among adolescents with IBS symptoms in the general population, with lower pain thresholds found to be independent of sex and comorbid pain. Our results suggest that central pain sensitization mechanisms in IBS may contribute to triggering and maintaining chronic pain symptoms.     

Lower airway bacterial colonization in asymptomatic smokers and smokers with chronic bronchitis and recurrent exacerbations

Bacterial colonization of the lower airways in patients with chronic bronchitis (CB) has been described mainly in patients with co-existing chronic obstructive pulmonary disease (COPD). Although smoking has been identified as a risk factor for bacterial colonization it is not known whether asymptomatic smokers (AS) can be colonized. The aim of this study was to study lower airway bacterial colonization in smokers with stable CB and recurrent exacerbations and compare with AS and healthy never-smokers (NS). Thirty-nine smokers with CB and recurrent exacerbations (median FEV1 85% of predicted normal), 10 AS and 10 NS, underwent bronchoscopy and a two-step bronchoalveolar lavage (BAL) procedure where the first portion (20 ml, 'pre-BAL') was recovered separately from the rest (140 ml, 'BAL'). The degree of oropharyngeal contamination of pre-BAL and BAL samples was evaluated by cytology. Semiquantitative bacterial cultures were performed on all samples. Higher bacterial numbers than 10(3) colony-forming units (cfu) x ml(-1) in BAL were found only in the two smoking groups. Using 10(3) cfu x ml(-1) as cut-off, 6/10 (60%) in the AS-, and 7/35 (20%) in the CB-group were colonized in the lower airways. In all, 29% of all smokers had bacterial colonization. Only bacteria belonging to the normal oropharyngeal flora were found. The proportion of samples with oropharyngeal contamination was significantly lower in BAL than in pre-BAL (5% vs. 21%, P=0.039). The proportion of sterile samples was significantly higher in BAL than in pre-BAL (49% vs. 26%, P=0.002). Lower airway bacterial colonization was found both in asymptomatic smokers and in patients with CB. Colonization with potential respiratory pathogens is uncommon in patients with CB and recurrent exacerbations without severe airflow obstruction. The two-step BAL procedure seems to decrease oropharyngeal contamination.     

Prognostic significance of recurrent chromosomal aberrations detected by comparative genomic hybridization in sporadic colorectal cancer

Colorectal carcinomas are characterized by frequent recurrent gains and losses of chromosomal material, especially gains of chromosome arms 20q and 13q, and losses of chromosome arms 18q and 4q. These may be important in the development and progression of colorectal carcinomas. Chromosomal aberrations detected by comparative genomic hybridization in 67 sporadic colorectal carcinomas were examined for their possible associations with patient survival. Dukes' stage, tumor DNA ploidy status, and TP53 genotype/phenotype were also examined for the same. Patients with losses of chromosomal arms 1p, 4q, 8p, 14q, or 18q or gain of chromosomal arm 20q had significantly shorter survival times than those without these aberrations (univariate relative risk 3.45, 2.71, 3.32, 3.26, 3.32, 3.91, respectively), as did patients with more than six chromosomal aberrations per tumor than those with fewer than six aberrations (univariate relative risk 3.26, P = 0.013). DNA aneuploidy and Dukes' stage C + D resulted in poor patient survival (univariate relative risk 3.58, 3.39, respectively). Dukes' stage C + D, 1p loss and 8p loss emerged as the only independent prognostic parameters (relative risk 3.22, 2.53, 2.45, respectively) when entered into multivariate survival analysis together with other significant parameters from univariate survival analysis. Loss of chromosome arm 1p, 4q, 8p, 14q, or 18q or gain of chromosome arm 20q thus results in shortened survival times in colorectal cancer patients. 1p loss and 8p loss were shown to be independent predictors of poor prognosis.