COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy

Type IV collagen α1 and α2 chains form heterotrimers that constitute an essential component of basement membranes. Mutations in COL4A1, encoding the α1 chain, cause a multisystem disease with prominent cerebrovascular manifestations, including porencephaly, bleeding-prone cerebral small vessel disease, and intracranial aneurysms. Mutations in COL4A2 have only been reported in a few porencephaly families so far. Herein, we report on a young adult patient with recurrent intracerebral hemorrhage, leukoencephalopathy, intracranial aneurysms, nephropathy, and myopathy associated with a novel COL4A2 mutation. We extensively investigated a 29-year-old male patient with recurrent deep intracerebral hemorrhages causing mild motor and sensory hemisyndromes. Brain MRI showed deep intracerebral hemorrhages of different age, diffuse leukoencephalopathy, multiple cerebral microbleeds and small aneurysms of the carotid siphon bilaterally. Laboratory work-up revealed significant microscopic hematuria and elevation of creatine-kinase. Genetic testing found a de novo glycine mutation within the COL4A2 triple helical domain. The presented case completes the spectrum of cerebral and systemic manifestations of COL4A2 mutations that appears to be very similar to that in COL4A1 mutations. Therefore, we emphasize the importance of screening both COL4A1 and COL4A2 in patients showing recurrent intracerebral hemorrhage of unknown etiology, particularly if associated with leukoencephalopathy.     

The suppression of endogenous adrenalin in the prolongation of ketamine anesthesia

This study investigated whether or not the anesthetic effect of ketamine in rats is dependent on adrenal gland hormones. The study was performed on two main rat groups, intact and adrenalectomized. Rat were divided into subgroups and given appropriate doses of ketamine, metyrapone or metyrosine. Durations of anesthesia in the groups were then recorded. Endogenous catecholamine levels were measured in samples taken from peripheral blood. This experimental results showed that ketamine did not induce anesthesia in intact rats at doses of 15 or 30 mg/kg, and that at 60 mg/kg anesthesia was established for only 11 min. However, ketamine induced significant anesthesia even at a dose of 30 mg/kg in animals in which production of endogenous catecholamine (adrenalin, noradrenalin dopamine) was inhibited with metyrosine at a level of 45–47%. Ketamine at 60 mg/kg in animals in which endogenous catecholamine was inhibited at a level of 45–47% established anesthesia for 47.6 min. However, ketamine at 30 and 60 mg/kg induced longer anesthesia in adrenalectomized rats with higher noradrenalin and dopamine levels but suppressed adrenalin production. Adrenalin plays an important role in the control of duration of ketamine anesthesia, while noradrenalin, dopamine and corticosterone have no such function. If endogenous adrenalin is suppressed, ketamine can even provide sufficient anesthesia at a 2-fold lower dose. This makes it possible for ketamine to be used in lengthy surgical procedures.     

Histopathology of tenosynovium in trigger fingers

Stenosing flexor tenosynovitis, trigger finger, is a common clinical disorder causing painful locking or contracture of the involved digits, and most instances are idiopathic. This problem is generally caused by a size mismatch between the swollen flexor tendon and the thickened first annular pulley. Although hypertrophic pulleys have been histologically and ultrasonographically detected, little is known about the histopathology of the tenosynovium covering the tendons of trigger fingers. We identified chondrocytoid cells that produced hyaluronic acid in 23 (61%) fingers and hypocellular collagen matrix in 32 (84%) fingers around the tenosynovium among 38 specimens of tenosynovium from patients with trigger fingers. These chondrocytoid cells expressed the synovial B cell marker CD44, but not the chondrocyte marker S‐100 protein. The incidence of these findings was much higher than that of conventional findings of synovitis, such as inflammatory infiltrate (37%), increased vascularity (37%), hyperplasia of synovial lining cells (21%), or fibrin exudation (5%). We discovered the following distinctive histopathological features of trigger finger: hyaluronic acid‐producing chondrocytoid cells originated from fibroblastic synovial B cells, and a hypocellular collagen matrix surrounding the tenosynovium. Thus, an edematous extracellular matrix with active hyaluronic acid synthesis might increase pressure under the pulley and contribute to the progression of stenosis.     

Alterations to Titanium Surface Depending on the Fluorides and Abrasives in Toothpaste

Fluoride and abrasives in toothpastes may cause corrosion and deterioration of the titanium used for implants and other prostheses. The purpose of this study was to investigate how the presence or absence and types of fluoride and abrasives affected the titanium surface texture. Brushing with toothpastes was performed on pure-titanium discs using an abrasive testing machine. Unprocessed titanium discs without brushing were used as control samples. Surface roughness, color, and gloss of titanium were measured and the differences compared with the control were analyzed. Additionally, titanium surfaces and abrasives in toothpastes were observed using a scanning electron microscope to compare the surface texture of each sample. Some toothpastes (abrasive+) significantly increased the difference in surface roughness, color, and gloss, compared with ultrapure water. Toothpaste (fluoride+/abrasive+) that had many polygonal abrasive particles led to the largest color differences and exhibited notable scratches and a larger number of contaminant- or corrosion-like black spots. In contrast, brushing with toothpaste without fluoride or abrasives (fluoride−/abrasive−) caused little change to the titanium surface. These results suggest that both fluoride and abrasives in toothpaste used for brushing may be factors that affect surface texture and corrosion resistance of titanium.     

Peptide vaccination for patients with melanoma and other types of cancer based on pre-existing peptide-specific ctotoxic T-lymphocyte precursors in the periphery

Identification of antigenic peptides expressed on cancer cells enables us to treat cancer patients with peptide-based immunotherapy. Although optimal protocols for peptide-based vaccines have not yet been elucidated, boosting the immune system could be a better approach than priming the immune system to elicit prompt and potent peptide-specific T-cell responses in cancer patients. With this possibility in mind, the authors undertook a clinical trial in which cancer patients were vaccinated with peptides (maximum 4) after confirmation of pre-existing peptide-specific cytotoxic T-lymphocyte (CTL) precursors in the periphery. Fourteen patients (seven with melanoma and seven with other types of cancer) positive for either HLA-A24 or HLA-A2 were enrolled in this study. Fourteen and 16 peptides were used to screen for HLA-A24+ and HLA-A2+ patients, respectively. The vaccination was well tolerated, and the only adverse effects were local pain and fever. Kinetic analysis revealed that peptide-reactive CTLs increased after peptide vaccination in 7 of 14 patients. Immunoglobulin G (IgG) reactive to the administered peptides was detected in 2 patients before vaccination, although it became detectable in 8 of the other 12 patients after the peptide vaccination. Stable disease for more than 6 months was observed in five patients (one with melanoma and four with other types of cancer); all of these patients showed increased levels of peptide-specific IgG. These results indicate that peptide vaccination of patients showing evidence of pre-existing peptide-specific CTL precursors can be applied in further clinical trials aimed at the treatment of melanoma and other types of cancer.     

Cytomegalovirus (CMV) antigenaemia for rapid diagnosis and monitoring of CMV-associated disease after bone marrow transplantation

A technique for the rapid detection of cytomegalovirus (CMV) antigen-positive blood leucocytes (CMV antigenaemia) was evaluated in 15 marrow transplant patients as a means of diagnosis and for monitoring CMV-associated disease. CMV antigenaemia was determined by direct immunoperoxidase staining of leucocytes with a peroxidase-labelled monoclonal antibody, HRP-C7, which binds an immediate-early antigen of human CMV.
CMV antigenaemia occurred in 7/15 marrow transplant patients (47%) and was initially detected between 4 and 6 weeks after transplantation. CMV-associated diseases developed in 3/15 patients (20%). All patients with CMV-associated disease had a relatively large number of CMV antigen-positive leucocytes, exceeding 10 per 50000 white blood cells (WBCs). In the remaining 12 patients, CMV antigen-positive leucocytes were less than 10 per 50000 WBCs or were undetectable. CMV-associated disease did not develop in these patients during the period of monitoring. CMV antigen-positive leucocytes were detected more frequently in patients who developed acute graft-versus-host disease (GVHD) or haemorrhagic cystitis than in those without such complications. CMV antigens were detectable from 1 to 4 weeks before the onset of CMV-associated disease which allowed initiation of ganciclovir treatment at an early stage. The degree of CMV antigenaemia paralleled the clinical symptoms and signs, higher degrees of antigenaemia being associated with more significant disease. Thus, the detection of CMV antigen-positive blood leucocytes is useful for the diagnosis and monitoring of CMV-associated disease following bone marrow transplantation.     

Detection of artificial demineralization bordering different types of laminate veneers using visual inspection and storage phosphor radiography

Objective

The objective of this study is to compare the diagnostic accuracy of visual inspection (VI) and storage phosphor plate (SPP) radiography for the detection of artificial demineralization bordering different laminate veneers.

Materials and methods

Twenty human maxillary canine teeth were prepared. All-ceramic (A) and hybrid ceramic (H) laminate veneers were fabricated and luted. Veneered teeth were covered except for a circular window on the proximal surface bordering restorations. Teeth were kept in acetic acid buffer to create demineralization and imaged with a SPP system. Ten observers evaluated all teeth first visually then with SPP images for the presence/absence of demineralization. Teeth were examined using scanning electron microscopy (SEM) as well. The accuracy was expressed as the area under the ROC curves (A _z). Pair-wise comparisons were performed using two-way ANOVA and post hoc t test (p?=?0.05). Fleiss kappa (κ) was used for agreement.

Results

SPP radiography was better than the VI for both veneers (p?=?0.004). The A _zs of two veneers were different for both VI (p?<?0.005) and SPP (p?<?0.005). SEM evaluation revealed lesions confined to enamel. κ was fair for H, and fair to moderate for A. Agreement was higher for the radiographic evaluation for both veneers.

Conclusion

Enamel demineralizations bordering hybrid and ceramic laminate veneers can be detected better with SPP radiography than VI and detectability was better for all-ceramic veneers than the hybrid ceramic ones.

Clinical relevance

Early detection of enamel demineralizations bordering laminate veneers would result in time-saving and less-invasive treatment methods; therefore, SPP radiography may be recommended in clinically suspicious cases since it provides better diagnostic accuracy.