Erythematous and reticular forms of oral lichen planus and oral lichenoid reactions differ in pathological features related to disease activity

BACKGROUND: Common clinical forms of oral lichen planus (OLP) and oral lichenoid reactions (OLR) are erythematous (ERY) or reticular (RET). The purpose of this study was to find histopathological changes that differ between these forms. METHODS: Epithelial thickness, epithelial proliferation rate, apoptosis, and HLA-DR expression were compared among 10 reticular and 12 erythematous lesions, and 11 normal oral mucosa samples (NOM). RESULTS: The epithelium in ERY was thinner than in NOM, whereas RET showed values between ERY and NOM. Cell proliferation increased significantly in ERY as compared with RET and NOM, with no difference between RET and NOM. Relative numbers of epithelial cell nuclei displaying visible chromatin condensation were reduced in ERY form. CONCLUSIONS: The markedly increased cell proliferation in ERY supports the notion that this form displays a higher disease activity as compared to RET. It can therefore be important to study each disease form separately.     

Cerebrospinal fluid immunoglobulins and beta 2-microglobulin in lymphoproliferative and other neoplastic diseases of the central nervous system

Humoral immune aberrations may occur in the cerebrospinal fluid (CSF) of patients with lymphoproliferative and other neoplastic diseases infiltrating the central nervous system (CNS). Such aberrations may be of diagnostic importance. We therefore studied CSF and serum from 47 patients with lymphoproliferative diseases and from 16 patients with various nonlymphoid neoplasias; 17 patients and 12 patients, respectively, had neoplastic CNS involvement. Elevated CSF IgM index and oligoclonal IgG bands in CSF and serum were commonly found, especially in patients with CNS involvement. Cerebrospinal fluid IgG and IgA indexes were usually normal. Increased CSF to serum albumin ratio, reflecting blood-brain barrier dysfunction, and increased CSF beta 2-microglobulin concentration were most common in patients with CNS involvement. The results indicate that neoplastic CNS disease should be borne in mind when CSF humoral immune aberrations are found.     

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.     

Disorders of color perception in subtoxic and toxic digoxin and serum digoxin concentrations

Using the Farnsworth-Munsell 100-hue test, investigations were carried out in 14 patients with subtoxic to toxic serum concentrations of digoxin (greater than 2.0 ng/ml) and 13 patients with subtoxic to toxic serum concentrations of digitoxin (greater than 30 ng/ml), in order to detect color vision deficiencies related to serum levels of digitalis. As compared to the control group (n = 24) the total error scores were significantly increased for both glycosides and all serum level ranges. No evidence was found indicating that digoxin and digitoxin influence color vision differently. The FM 100-hue test indicated definite improvements in the digoxin group within one day of discontinuing the glycosides, while the digitoxin group only started to normalize a week later. The results are discussed, taking the different pharmacokinetics of the two digitalis glycosides into account.     

Peroneal nerve palsy after early cast application for femoral fractures in children.

The incidence and contributing factors associated with post-casting peroneal nerve palsy were examined in a series of 110 consecutive pediatric femoral shaft fractures treated with early hip spica cast application. Four patients with peroneal nerve palsy were identified. All four had 90 degrees/90 degrees casts placed and underwent cast wedging for alignment. All palsies resolved with immediate cast removal. Other treatment options for certain femur fractures with significant initial shortening should be considered. We advise pre- and post-cast neurologic examination and avoidance of forceful distraction. Fracture manipulation, through wedging, should be delayed.     

Free insulin profiles in insulin-dependent diabetics treated with one or two insulin injections per day

Twenty-four hour profiles of free insulin and blood glucose were determined in 12 healthy controls and 10 insulin-dependent diabetics treated with insulin regimens based on intermediate-acting insulin injected subcutaneously once or twice a day. The diabetics were ambulatory and in a good glycemic control, i.e. without hyperglycemic symptoms or frequent hypoglycemias and with HbA1 less than 9% (reference value 5.9-7.8%). Body weight was normal and median age (32 years) was the same in both groups. Free insulin was determined after polyethylene glycol precipitation of antibody-bound insulin. The controls had a low basal insulin level (median fasting value 3.9 mU/l) and postprandial peaks with a maximum within 30-60 min. There was no rise in plasma free insulin or blood glucose in the early morning hours. The free insulin profiles in the diabetics were highly unphysiological with hyperinsulinemia between the meals and during the night. The highest plasma free insulin value during the 24 hours was reached before lunch (approximately 5-fold compared to normals, p less than 0.01). Postprandially the free insulin concentrations did not reach the peak levels of the normals. After breakfast, blood glucose rose considerably in the diabetics (p less than 0.02 compared to normals) while the rise after lunch and dinner was not higher than in the healthy controls. The difficulties in glycemic control in the diabetic group, i.e. a blood glucose rise after breakfast and hypoglycemias in some patients, could largely be explained by the unphysiological insulin profiles.     

Modification of collagen matrices for enhancing angiogenesis

The vascularization of engineered tissues in many cases does not keep up with the ingrowth of cells. Nutrient and oxygen supply are not sufficient, which ultimately leads to the death of the invading cells. The enhancement of the angiogenic capabilities of engineered tissues therefore represents a major challenge in the field of tissue engineering. The immobilization of angiogenic growth factors may be useful for enhancing angiogenesis. The most potent angiogenic growth factor specific to endothelial cells, vascular endothelial growth factor (VEGF), occurs in several splice variants. The variant with 165 amino acids both has a high angiogenic activity and a high affinity for heparin. We therefore incorporated heparin molecules into collagen matrices by covalently cross-linking them to amino functions on the collagen. Physical binding of VEGF to the heparin may then prevent a rapid clearance from the implant, while the release rate may become coupled to the degradation of the collagen matrix. The modified matrices were characterized by determination of the extent of the heparin immobilization, the in vitro degradation rate by collagenase. For testing the angiogenic properties, non-modified and heparinized collagen specimens were--either loaded with VEGF or non-loaded--subcutaneously implanted on the back of rats. Specimens were explanted after varying periods of implantation, the dry weights and the hemoglobin contents, as well as immunostained histological sections were evaluated: heparinized collagen matrices loaded with VEGF are vascularized to a substantially higher extent as compared to non-modified matrices.     

CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion

DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.     

Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder.

The clinical polysomnographic (PSG) reports of 2,650 consecutive adults studied during 41 months were reviewed retrospectively to identify all patients treated with fluoxetine or tricyclic antidepressants. The PSG reports of four other adult groups were also reviewed: periodic limb movement (PLM) disorder (n = 28); sleep terror/sleepwalking (ST/SW) (n = 54); rapid eye movement (REM) sleep behavior disorder (RBD) (n = 70); patients with clinically unremarkable sleep during two consecutive PSG studies (n = 30). Standard PSG recording and scoring methods were employed. A total of 1.5% (n = 41) and 2.0% (n = 52) of patients were receiving fluoxetine or tricyclics (amitriptyline or nortriptyline, n = 31; imipramine or desipramine, n = 16; protriptyline or trimipramine, n = 5). A selective association between fluoxetine and extensive, prominent eye movements in nonrapid eye movement (NREM) sleep was detected, utilizing Fisher's exact one-tailed statistic (p less than 0.00001 for each comparison). The detection rates were fluoxetine, 48.8% (20/41); tricyclics, 5.8% (3/52); RBD, 4.3% (3/70); objectively normal sleepers, 3.3% (1/30); PLM, ST/SW, 0% (0/82). These groups had similar mean ages (31.5-45.4 years) and gender distributions (50.0-60.7% male), apart from RBD. The effect of fluoxetine, a potent and specific serotonin reuptake inhibitor, on NREM eye movements is postulated to derive from potentiation of serotonergic neurons that inhibit brainstem "omnipause neurons", which, in turn, inhibit saccadic eye movements, thus resulting in disinhibited release of saccades. In addition, a 31-year-old man with obsessive-compulsive disorder developed RBD soon after starting fluoxetine therapy, which persisted at PSG study 19 months after fluoxetine discontinuation.