Seizure-induced changes in the permeability of the blood-brain barrier following administration of anticholinesterase drugs to rats

Powerful inhibitors of acetylcholinesterase (phospholine iodide, paraoxon, and Soman) were used either separately or in combination with an anesthetizing drug (nembutal), an acetylcholine antagonist (atropine sulfate), or a convulsive drug (metrazole) to study the resistance of the blood-brain barrier to their effects. On the basis of measurements of acetylcholinesterase inhibition in rat brain stem and corpus striatum, it was concluded that these anticholinesterase drugs increased the permeability of the blood-brain barrier, provided that seizures were manifested shortly after administration of these drugs. Rats that were treated prophylactically with either nembutal or atropine sulfate did not convulse and, consequently, damage to the blood-brain barrier integrity was reduced significantly, despite a high degree of acetylcholinesterase and butyrylcholinesterase inhibition. It is suggested that anticholinesterase drugs enhance brain AChE inhibition by inducing strong convulsions and, thereby, increase their own penetration through the blood-brain barrier. It does not appear likely that acetyl- or butyrylcholinesterase located in the walls of the brain capillaries is involved in maintenance of the blood-brain barrier.     

H-2 gene products influence susceptibility of target thyroid gland to damage in experimental autoimmune thyroiditis

The restriction of the pathogenesis of experimental autoimmune thyroiditis (EAT) by H-2 gene products was investigated. EAT was induced by injecting thyroglobulin extract plus adjuvant into F₁, hybrid mice that had been implanted under the kidney capsules with thyroid glands originating from either the EAT-susceptible or -resistant parental strain mice. We found relative H-2 restriction of thyroid damage to those glands originating from the H-2-susceptible parental strain. H-2 restriction of damage at the level of the target thyroid gland implicates cytotoxic effector T lymphocytes as a pathogenic agent of EAT.     

Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy

Background

Multifocality is an important factor when recommending surgery for papillary thyroid cancer (PTC). The aim of this study is to assess the incidence and characterize the spread pattern of multifocal PTC (mPTC) in patients undergoing total thyroidectomy.

Methods

All thyroidectomies performed between 2003 and 2008 were reviewed identifying 289 patients. Data were obtained for demographics, clinical data, and histopathological findings.

Results

Of the patients with papillary carcinoma, mPTC was identified in 150 patients (57%), of which 71% had lesions in the contralateral lobe. There were no significant differences in multifocality rate for gender, pathology type, and all tumor size subgroups including ≤1 cm. Pathology examination of representative sections versus the entire gland examination resulted in a significantly lower incidence of contralateral disease (P = .04).

Conclusions

Multifocal and contralateral lesions are common in PTC and their incidence is not related to tumor size. Pathology entire gland examination is strongly recommended to properly assess the rate of mPTC.     

Hypnotic relaxation vs amitriptyline for tension-type headache: let the patient choose

(Headache 2012;52:785‐791) Background.— Although both pharmacological and behavioral interventions may relieve tension‐type headache, data are lacking regarding treatment preference, long‐term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting. Objective.— To describe patient choice, long‐term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue. Design.— Patients presenting to the headache clinic with a diagnosis of tension‐type headache that justified prophylactic therapy (frequent episodic tension‐type headache or chronic tension‐type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross‐over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow‐up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality‐of‐life parameters. Results.— Ninety‐eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty‐three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P = .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy‐four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P = .16). Long‐term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued receiving their initial treatment. Conclusions.— HR treatment was a more popular choice among patients. Patients choosing HR reported greater symptom relief than those choosing AMT and were found to have greater treatment compliance. Patients receiving HR were less likely to change treatments. HR practiced by a neurologist is feasible in a standard neurological outpatient clinic setting; HR training should be considered for neurologists involved in headache treatment.     

Coronary calcium by spiral computed tomography predicts cardiovascular events in high-risk hypertensive patients

OBJECTIVE: The ability of coronary artery calcium (CAC) to predict coronary events has been shown in several studies. We aimed to investigate the hypothesis that CAC as assessed by dual slice spiral computed tomography (DSCT), is an independent risk factor for cardiovascular events in hypertensive patients. METHODS: We followed 446 participants of INSIGHT (International Nifedipine Study Intervention as Goal for Hypertension Therapy) calcification study, for the incidence of cardiovascular events as a function of CAC and other factors. All were hypertensive, without coronary artery disease (CAD), ages > 55 years and with at least one more major cardiovascular risk factor. All underwent a baseline DSCT and were followed for a mean period of 3.8 +/- 0.4 years. All events were documented while the scheduled visits and confirmed by the INSIGHT critical event committee. RESULTS: Follow-up was conducted on all participants. 294 patients (66%) had CAC at baseline. Forty-seven patients experienced a first cardiovascular event: acute myocardial infarction (MI), 16; sudden cardiac death, two; unstable angina resulting in revascularization, 14; stroke, 15. The incidence of first cardiovascular events was 3.7 times higher among those who had CAC at baseline than among those who had no CAC (14.5% (41 of 294) versus 3.9% (6 of 152)). Patients who experienced an event were more likely to be males, had had higher prevalence of peripheral vascular disease, longer duration of hypertension, and had higher levels of systolic blood pressure (SBP), glucose, creatinine and uric acid. Adjusting for these covariates, CAC (total coronary calcium score (TCS) > 0) independently predicted cardiovascular events with an odds ratio (OR) of 2.76 [95% confidence interval (CI) 1.09-6.99, P = 0.032]. CONCLUSION: The presence of CAC predicts cardiovascular events in high-risk asymptomatic hypertensive patients.     

Post-transcriptionally Regulated Expression System in Human Xenogeneic Transplantation Models

Cells have developed a mechanism to discriminate between premature termination codons (PTCs) and normal stop codons during translation, sparking vigorous research to develop drugs promoting readthrough at PTCs to treat genetic disorders caused by PTCs. It was posed that this concept could also be applied to regulated gene therapy protocols by incorporating a PTC into a therapeutic gene, so active protein would only be made after administration of a readthrough agent. The strengths of the system are highlighted here by results demonstrating: (i) background expression levels were reduced to 0.01% to 0.0005% of wild type in unselected mass populations of cells depending upon the specific stop codon utilized and its position within the gene; (ii) expression levels responded well to multiple “On” and “Off” regulation cycles in vivo in human xenograft systems; (iii) the level of induction approached three logs using aminoglycoside activators including NB54, a newly synthesized aminoglycoside with significantly reduced toxicity; and (iv) expression levels could be appreciably altered when employing different promoters in a variety of cell types. These results strongly support the contention that this system should have important clinical applications when tight control of gene expression is required.     

Pulsed carbon dioxide laser ablation of burned skin: In vitro and in vivo analysis

Pulsed lasers produce efficient and precise tissue ablation with limited residual thermal damage. In this study, the efficiency of pulsed CO₂ laser ablation of burned and normal swine skin was studied in vitro with a mass loss technique. The heats of ablation for normal and burned skin were 2,706 and 2,416 J/cm³ of tissue ablated, respectively. The mean threshold radiant exposures for ablating normal skin and eschar were 2.6 J/cm² and 3.0 J/cm², respectively. Radiant exposures greater than 19 J/cm² produced a plasma, which decreased the efficiency of laser ablation. Thus the radiant exposures for efficient ablation range from 4 to 19 J/cm², and within this radiant exposure range 20–40 μm of tissue are ablated per pulse. We also examined, on a gross and histo-pathologic basis, in vivo burn eschar excision with a pulsed CO₂ laser. The laser allowed bloodless excisions of full thickness burns on the backs of male hairless rats. The zone of thermal damage was approximately 85 μm over the subjacent fascia. The pulsed CO₂ laser can ablate burn eschar efficiently, precisely, and bloodlessly and may prove valuable for the excision of burned and necrotic tissue.