Modulation of Slow Cortical Potentials by Instrumentally Learned Blood Pressure Responses

We assessed whether instrumentally-learned pressor responses inhibit electrocortical acitivity, as predicted by learning theories of idiopathic hypertension. Subjects received beat-by-beat feedback for increases and decreases in mean arterial pressure measured from the finger (Peñáz method). Slow potentials were recorded from the midsagittal line during the final training session. Also recorded at this time were heart rate, eye movements, respiration, and post-session verbal reports of the subject's control strategies. Thirteen of 14 subjects differentiated blood pressure increases and decreases at p<.05 or better during the final session (within-subject discriminative operant procedure). Slow potentials were less negative on blood pressure increase compared to decrease trials at all midsagittal sites (p<.02), indicating relative cortical inhibition by pressor responses. This effect occurred even though subjects reported tensing of muscles on increase trials (p<.01), a behavioral activity previously associated with augmented rather than diminished cortical negativity. On increase trials slow potentials shifted toward positivity just prior to heart rate deceleration (the latter effect confirming activation of the baroreceptors).     

Impact of insulin-like growth factor receptor-I function on angiogenesis,growth, and metastasis of colon cancer

Insulin-like growth factors and their principal receptor, IGF-I receptor (IGF-IR), are frequently expressed in human colon cancers and play a role in preventing apoptosis, enhancing cell proliferation, and inducing expression of vascular endothelial growth factor (VEGF). The role of IGF-IR in regulating angiogenesis and metastases of human colon cancer has not been elucidated. To determine the in vitro and in vivo effects of IGF-IR in human colon cancer growth and angiogenesis, human KM12L4 colon cancer cells were transfected with a truncated dominant-negative form of IGF-IR (IGF-IR dom-neg). IGF-IR dom-neg-transfected cells demonstrated markedly decreased constitutive expression of VEGF mRNA and protein. Subcutaneous injections of IGF-IR dom-neg-transfected cells in nude mice led to significantly decreased tumor growth (p < 0.05) that was associated with decreased tumor cell proliferation, VEGF expression, and vessel count and with increased tumor cell apoptosis (p < 0.05 for all parameters compared with controls). In addition, pericyte coverage of endothelial cells was significantly decreased in tumors from IGF-IR dom-neg-transfected cells. Following this observation, we demonstrated in vitro that vascular smooth muscle cells migrated significantly less in conditioned medium derived from IGF-IR dom-neg-transfected cells compared with medium from control cells. After splenic injections, IGF-IR dom-neg transfectants failed to produce liver metastases, in contrast to parental cells and mock transfectants (p < 0.05). In addition, IGF-IR dom-neg-transfected cells failed to form liver tumors after direct injection into the liver. These studies demonstrate that the IGF-IR plays an important role in multiple mechanisms that mediate the growth, angiogenesis, and metastasis of human colon cancer. IGF-IR is a valid target for the therapy of human colon cancer.     

Heterogeneity for mutations in medium chain acyl-CoA dehydrogenase deficiency in the UK population

MCAD is the commonest inherited disorder of fatty acid oxidation. We have sought for and studied 21 affected children from 18 families within the UK. In 14 families the children are homozygous for the G985 mutation. In three families the children are compound heterozygotes for G985 and thus carry another and unknown mutation. In one family the child does not carry the G985 mutation on either allele. The carrier incidence of the G985 mutation is 1 in 68, which suggests that the natural history of MCAD deficiency deserves further study.     

Value-impregnated factual claims and slippery-slope arguments

Slippery-slope arguments typically question a course of action by estimating that it will end in misery once the first unfortunate step is taken. Previous studies indicate that estimations of the long-term consequences of certain debated actions, such as legalizing physician-assisted suicide, may be strongly influenced by tacit personal values. In this paper, we suggest that to the extent that slippery-slope arguments rest on estimations of future events, they may be mere rationalizations of personal values. This might explain why there are proponents even for strikingly poor slippery-slope arguments.     

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable,locally advanced NSCLC patients

Investigational New Drugs - The aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in...     

Outcome after carpal tunnel release: impact of factors related to metabolic syndrome

Objective: The standard surgical treatment of carpal tunnel syndrome (CTS), with an open carpal tunnel release, is reported to relieve symptoms in most patients. In a retrospective observational study, outcome after open carpal tunnel release was evaluated, focusing on factors related to the metabolic syndrome: diabetes, hypertension, obesity (BMI ≥30) and statin treatment.

Methods: Results from 493 out of 962 patients (531/1044 hands) operated for CTS during 18 months that had filled in QuickDASH questionnaires before and 1-year after surgery were included in the study.

Results: Patients with diabetes (n?=?76) had higher QuickDASH scores pre- (56 [36–77]; i.e. median [interquartile range]) and postoperatively (31 [9–61]) compared to patients without diabetes (48 [32–66]; p?p?10 (74% vs 61%; p?Conclusions: Patients with diabetes without neuropathy, as well as patients with hypertension, obesity or statin treatment, and CTS can expect the same effects of open carpal tunnel release as otherwise healthy patients. Patients with diabetic neuropathy and CTS did not experience the same improvement as otherwise healthy patients and should be informed about the risk of an unsatisfactory outcome.