Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

Background  

The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site.     

Decoronation of an ankylosed permanent incisor: alveolar ridge preservation and rehabilitation by an implant supported porcelain crown

Abstract –  Replacement resorption and ankylosis are frequently diagnosed following severe dental trauma. The complications that may develop as a result of ankylosis of a permanent incisor in children and adolescent include: esthetic compromise, orthodontic complications because of: arch irregularity; lack of mesial drift; tilting of adjacent teeth, arch length loss and local arrest of alveolar ridge growth. To avoid such complications, an ankylosed tooth should be removed before the changes become so pronounced that they compromise future prosthetic treatment. The purpose of this article was to present a case of preservation of the alveolar ridge for implant rehabilitation by utilizing decoronation for the treatment of a young permanent central incisor. An implant was inserted, without any bone augmentation procedures, followed by prosthetic porcelain crown rehabilitation. We conclude that treatment of an ankylosed young permanent incisor by decoronation may maintain the alveolar bone ridge width, height and continuity, and facilitate future rehabilitation with minimal, if any, ridge augmentation procedures.     

Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer.

PURPOSE: To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. EXPERIMENTAL DESIGN: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. RESULTS: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21 of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. CONCLUSIONS: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway-related genetic alterations and BRAF mutation. The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers.     

An explanation of the mechanism of preventing pregnancy by IUCD

Serum acid phosphatase (AcPh) levels in a group of 63 women using an IUD, as compared with those of 30 women in a control group, are presented. In the test group, serum prolactin (PRL) levels before IUD insertion and 1-24 months of IUD use in utero was also examined. The presence of an IUD in utero resulted in an increase of serum AcPh (p0.01) compared with the control group--irrespective of type of device used--as well as in an increase of PRL level (p0.001). Among the types of IUD examined, it seems that the Nova T had the highest effect (P=0.05). The increase in AcPh, a lysosomal enzyme marker, prevents the nidation of the blastocyst in the endometrium through an effect on the endogenous prostaglandin synthesis which induces uterine contractions and luteolysis. At the same time, the increase in PRL level interferes with ovulation--the other factor which induces temporary infertility. The way in which PRL levels increase due to the presence of an IUD in utero, and how the signal is carried to the central nervous system is described.     

Investigating the criterion validity of psychiatric symptom scales using surrogate marker validation methodology

This work investigates whether techniques that are generally used for the validation of surrogate markers in clinical trials can be applied in the validation of psychiatric health measurements (often scales) and more generally to investigate relationships between treatment effects on different measurements. However, the categorical nature of some scales makes these techniques inapplicable in the way they were originally defined. In this work, we show a possible extension of this methodology to the setting in which one of the scales is an ordinal categorical variable. When psychiatric health measurements are either developed or used in a new population, reliability and validity must be investigated. Reliability, more specifically internal consistency, test-retest reliability, and inter-rater reliability, is focused on the reproducibility of the measurement. Validity is defined as the degree to which the scale measures what it purports to measure. This can be performed through the analysis of content, construct, and criterion validity. We argue that recent methodology, in particular developed to study surrogate endpoints, can be used to examine criterion validity, concurrent validity, and predictive validity. In concurrent validity, we correlate the measurement with a criterion measure, both of which are given at the same time. In predictive validity, the criterion will not be available to some point in time in the future. The surrogate methods were applied on pooled data from five trials in schizophrenia.     

Expression of matrix metalloproteinases,sICAM-1 and IL-8 in CSF from children with meningitis

The combined expression of the inflammatory mediators, matrix metalloproteinases (MMPs), soluble form of intracellular adhesion molecule ICAM-1 (sICAM-1) and interleukin (IL)-8, was evaluated in children infected with bacterial or viral meningitis. MMP-2 and IL-8 were detected in all CSF samples and were enhanced in both bacterial and viral infected samples, compared to those from control children. The expression of MMP-9 as well as sICAM-1 was not detected in control CSF while observed in viral infected and further elevated in bacterial infected samples. This pilot study supports a role for MMPs, IL-8 and sICAM in infectious meningitis and suggests further research to determine their possible use as biomarkers for various forms of meningeal infection as well as the use of their specific antagonists as potential therapeutic agents for central nervous system (CNS) inflammatory processes.     

Partial replacement of the tricuspid valve by mitral homografts in acute endocarditis

Background. Seven patients with acute tricuspid endocarditis underwent partial replacement of the tricuspid valve using mitral homograft tissue. Valve function was evaluated at midterm.

Methods. Operative indications were uncontrolled sepsis in all cases associated with heart failure symptoms in 3 patients and septic pulmonary emboli in 2 patients. These patients were referred to our institution after a course of antibiotic treatment ranging from 7 to 12 weeks. Lesions found at the level of the anterior leaflet of the tricuspid valve were vegetations and rupture of more than half of the marginal cords in all patients. Vegetations were also found on the posterior leaflet in 5 patients. In all instances the septal leaflet was free of lesions. The aortic valve was involved in 4 patients and the pulmonary valve in 1 patient. All patients underwent resection of the anterior and posterior leaflets of the tricuspid valve with their corresponding papillary muscles leaving the septal leaflet in place. Replacement of the tricuspid valve was performed through a right longitudinal atrial access, using the anterior leaflet of a mitral homograft alone in 3 patients and the anterior leaflet with part of posterior leaflet in 4 patients. Associated procedures included aortic valve replacement by a homograft (n = 4) and pulmonary valve reconstruction (n = 1).

Results. No hospital deaths are reported. One late death, at 16 months, is reported after reoperation due to recurrent aortic valve endocarditis. At midterm (mean follow-up, 30 months) patients had excellent functional status and normal valvular function during echocardiographic studies.

Conclusions. We conclude that when the degree of tricuspid valve destruction prevents repair, partial homograft replacement can be used as an extension of the already existing reconstructive techniques, with excellent functional results.