E-cadherin and c-Met expression in actinic cheilits and lip squamous cell carcinoma

Objective: The aim of this study was to assess epithelial expression of E-cadherin and c-Met in normal lip, in actinic cheilitis and lip squamous cell carcinoma. Study Design: Biopsies of normal lip vermillion (NL, n=18), actinic cheilitis (AC, n=37), and lip SCC (n=22) were processed for E-cadherin and c-Met immunodetection. Epithelial and tumor cell expression was scored for each sample considering staining intensity and percentage. Results: E-cadherin expression was significantly reduced in AC and lip SCC as compared to normal lip (P<0.05), with a significant reduction in lip SCC as compared to AC (P=0.003). Expression of c-Met was significantly higher in AC and lip SCC as compared to NL (P<0.05), with a significant increase in lip SCC as compared to AC (P<0.0001). Conclusion: The results showed that epithelial E-cadherin expression is reduced and c-Met expression is increased as lip carcinogenesis progresses, suggesting that these proteins may be useful markers of malignant transformation.

Reduction of syndecan-1 expression during lip carcinogenesis.

BACKGROUND: Actinic cheilitis (AC) is an oral pre-cancerous lesion that sometimes develops into lip squamous cell carcinoma (SCC). Syndecan-1, a transmembrane heparan sulfate proteoglycan, modulates cell-proliferation, adhesion, migration and angiogenesis. Malignant epithelial cells often down-regulate their own syndecan-1 production, and are capable of inducing aberrant syndecan-1 expression in stromal cells. The aim of this study was to evaluate the variations in syndecan-1 expression during lip carcinogenesis, in normal lip (NL), AC and well-differentiated lip SCC. METHODS: Biopsies of NL vermillion (n = 19), AC (n = 23) and lip SCC (n = 24) were stained immunohistochemically for syndecan-1. RESULTS: Syndecan-1 expression was significantly reduced in AC and lip SCC as compared to NL (P < 0.05), with a significant reduction in lip SCC as compared to AC (P < 0.0001). In lip SCC lesions, syndecan-1 expression at the epithelium overlying the tumor was increased when compared to the tumor itself (P < 0.03), but was significantly reduced as compared to AC and NL (P < 0.001). CONCLUSION: The results showed that epithelial syndecan-1 expression is reduced as lip carcinogenesis progresses (NL>AC>lip SCC), suggesting that syndecan-1 could be a useful marker of malignant transformation in the lip.

Inattention, hyperactivity-impulsivity, academic skills and psychopathology in boys with and without haemophilia.

The aim of this study was to determine if symptoms of inattention (IN) and hyperactivity-impulsivity (HI) differ for boys with and without haemophilia and to determine if IN and HI are the essential behavioural dimensions on which the two groups differ. Using a quasi-experimental design, parents' and teachers' ratings of IN and HI for boys with and without haemophilia (ages 6-14 years) were compared. IN and HI were also assessed with a psychometric task, as were reading and math, psychopathology, and educational status via various techniques. Boys with haemophilia (n = 19) were rated higher on dimensions of HI and IN by teachers (P = 0.01, P = 0.02, respectively) but only on HI by parents (P = 0.01). In addition, the haemophilia group committed more impulsivity errors on a psychometric task (P = 0.01). Trends, but not statistically significant differences, were found on reading and math scores, and the haemophilia group had more special education participation. Compared to national norms, borderline range scores on the attention-deficit/hyperactivity disorder (ADHD)-related dimensions of HI and psychometrically measured impulsivity characterized the boys with haemophilia. Although not addressing formal diagnoses, this study found that boys with haemophilia risk ADHD-spectrum problems, especially HI, and special education participation, but not frank academic deficits.

Characterization of mast cell subpopulations in lip cancer.

BACKGROUND: Lip squamous cell carcinoma (SCC) is the most common form of oral cancer. Human mast cells (MCs), which are increased in lip SCC, are classified by their protease content in tryptase-positive (MC(T)) and tryptase/chymase-positive (MC(TC)). MC proteases are associated with tumor progression and angiogenesis. The aim of this study was to quantify and characterize MC subpopulations in lip SCC. METHODS: Serial sections from lip SCC (n = 21) and normal lip vermilion (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC subpopulation density and distribution. RESULTS: MC(T) and MC(TC) were increased in lip SCC when compared with normal lip (P < 0.0001), where MC(T) predominated over MC(TC) (P < 0.01). In lip SCC neither subpopulation predominated. Regarding distribution, MC(T) were higher than MC(TC) at the intratumoral stroma, whereas MC(TC) were higher than MC(T) at the peritumoral stroma (P < 0.01). CONCLUSIONS: The results suggest that MC subpopulations may contribute to lip SCC progression. While intratumoral MC(T) may stimulate angiogenesis, peritumoral MC(TC) may promote extracellular matrix degradation and tumor progression at the invasion front.

Increased mast cell density and protease content in actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a pre-malignant lesion caused by ultraviolet (UV) radiation and characterized by epithelial and connective tissue alterations. Mast cells (MCs), key contributors to solar elastosis in murine UV-irradiated skin, were characterized in order to assess their potential contribution to connective tissue degeneration in AC. METHODS: Actinic cheilitis (n = 15) and normal lip (n = 8) biopsies were stained immunohistochemically for tryptase and enzymehistochemically for chymase to determine MC density and protease content. MC subpopulations (i.e. MC(T) containing only tryptase, and MC(TC) containing chymase and tryptase) and their distribution were also determined. RESULTS: Mast cells and their proteases were increased in AC as compared with normal lip (P < 0.0001), and appeared degranulated especially around elastotic areas. MC(T) predominated over MC(TC) in AC and normal lip (P < 0.05). However, in AC MC(T) were increased in the epithelium/connective junction and connective area (P < 0.05), while in normal lip MC(T) predominated in connective and submucosal areas (P < 0.05). CONCLUSION: The results suggest that increased MC density and protease content may contribute to elastosis formation in AC. In addition, changes in MC(T) distribution may favor AC malignization.

An investigation of a modal-falsetto register transition hypothesis using helox gas.

This study concerned the effect of the first subglottal formant (F1') on the modal-falsetto register transition in males and females. Phonations using air and a helium-oxygen mixture (helox) were used in a comparative study to tease apart possible acoustic and myoelastic contributions to involuntary register transitions. Recordings of the first subglottal formant and its accompanying bandwidths, and the lower and upper shift point marking the outer boundaries of abrupt register transitions, were obtained via a neck-mounted accelerometer, and analyzed using spectrograms and power spectra on a K-5500 Sona-Graph. The four subjects had their hearing masked bilaterally with speech level noise to increase the likelihood of involuntary register transition via minimized auditory feedback. In three of the four test subjects registration was surmised to be primarily a laryngeal event, as evidenced by the similar frequency dependency of voice breaks in both air and helox. It may be hypothesized that subglottal resonance influenced register transition in the fourth subject, as voice breaks rose with helox-induced phonation; however, this result did not reach statistical significance. Therefore, in this experiment subglottal resonance was not found to have a significant influence on register transition as originally hypothesized.

Post-traumatic stress disorder and paralytic agents.

When a 38-year-old former critical care unit (CCU) nurse became critically ill, she required mechanical ventilation with pancuronium--a paralytic agent--as an adjunct. She also received intravenous morphine and diazepam for analgesia and sedation. Three weeks later, her condition much improved, paralytic agents were discontinued and the nurse was extubated. Familiar with treatment protocols, her caregivers and the environment, she felt comfortable sharing her perceptions of the previous three weeks with her colleagues.

Evaluation of capillary collection system for HbA1c specimens.

OBJECTIVE: We evaluated the accuracy and stability of a capillary HbA1c collection system for use with a high-performance liquid chromatography analyzer. RESEARCH DESIGN AND METHODS: The collection system requires that 5 ul blood is drawn into a calibrated capillary tube, which is then placed into a vial of stabilizing solution and sent for analysis. The study was conducted on simultaneously drawn capillary and venous blood specimens from 47 pediatric diabetes patients. Accuracy was determined by comparing the capillary to the venous HbA1c values. Stability was measured by analyzing 17 capillary specimens over 3 wk. RESULTS: There was excellent agreement between the capillary and venous HbA1c values (capillary 0.959, venous +0.494, R2 = 98.7%). The capillary HbA1c values were 0.2% higher than the venous HbA1c values and decreased gradually over time (0.1% HbA1c/week) when stored at room temperature. CONCLUSIONS: The Bio-Rad (Richmond, CA) collection system is accurate, stable, and simple to use.

The prevalence of anorexia nervosa, bulimia, and induced glycosuria in IDDM females.

Questionnaires were sent to 550 female patients aged 13 to 45, with insulin-dependent diabetes to determine the prevalence of eating disorders in this population. Seventy percent of the questionnaires were returned and analyzed. One percent of respondents met criteria for lifetime prevalence of anorexia nervosa, 16.2% for lifetime prevalence of bulimia, and 4.9% for induced glycosuria. Contrary to previous studies, the prevalence of bulimia and anorexia was within the range identified in the general population, although at the upper end of the range. The medical risks incurred by women with diabetes who have eating disorders, however, are substantially greater and warrant attention. The incidence of induced glycosuria is a significant problem for diabetes educators and health care providers working with women who have discovered a dangerous but effective way to lose weight.

Effects of a physical activity program on metabolic control and cardiovascular fitness in children with insulin-dependent diabetes mellitus.

The purpose of this investigation was to determine the effects of a regular vigorous physical activity program on children aged 5-11 yr with insulin-dependent diabetes mellitus (IDDM). The experimental group of children (N = 9) took part in a 30-min vigorous exercise program three times a week for 12 wk; the control group (N = 10) did not. Hemoglobin A1 (HbA1) and fasting blood glucose (FBG) were used to determine metabolic control. Oxygen consumption was evaluated by treadmill testing and analyses of expired air. The experimental group significantly (P less than 0.05) decreased their HbA1 and FBG while the control group showed no change. The experimental group significantly (P less than 0.05) increased their peak aerobic capacity (ml/kg . min) when compared with baseline values (47.14 +/- 1.94 versus 50.69 +/- 1.30). It was concluded that a carefully applied program of regular vigorous physical activity can beneficially influence metabolic control and cardiovascular fitness in young children with IDDM.

Suppressed responsiveness to gonadotropin-releasing hormone in girls with unsustained isosexual precocity.

Eleven girls, ages 10/12 to 76/12 years, were evaluated because of early and rapid breast development. Initial clinical presentations and serum gonadotropin or estradiol determinations did not differentiate patient types. However, patients could be divided into two groups based on their responses to synthetic gonadotropin-releasing hormone: Group A consisted of seven girls with suppressed or prepubertail-type responses, and Group B consisted of four girls with pubertal or adult-type responses. Subsequent evaluation revealed that Group A patients had intermittent or unsustained isosexual precocity, whereas Group B patients had isiopathic prococious puberty. During initial evaluation, increased serum or urinary estrogen values were noted in ten of ten patients who were studied. The greatest serum E2 values (162 and 117 pg/ml) were noted in two Group A patients; three months and two years later, those patients had normal prepubertal responses to GnRH and serum E2 values of less than 4 and 14 pg/ml, respectively. Unsustained sexual precocoity in girls may be secondary to autonomous ovarian production of estrogens, and the GnRH test may be useful in evaluation of girls with isosexual precocity.

Hypocalcemia, hypomagnesemia, and transient hypoparathyroidism during therapy with potassium phosphate in diabetic ketoacidosis.

The effects of intravenous administration of potassium phosphate in the treatment of diabetic ketoacidosis were studied in nine children, ages 9 9/12 to 17 10/12 yr. During phosphate infusion (20--40 meq/L of fluid), all children maintained normal serum concentrations of phosphorus. Transient hypocalcemia occurred in six and transient hypomagnesemia in five patients. One child developed carpopedal spasms refractory to intravenous infusion of calcium gluconate but responsive to intramuscular injection of magnesium sulfate. In three patients, serum levels of intact parathyroid hormone were low at the time of hypocalcemia, an observation that suggests transient hypoparathyroidism. This study indicates that the use of potassium phosphate as the sole source of potassium replacement might potentiate ketoacidosis-induced hypocalcemia through multiple mechanisms.

Effect of cortisol treatment on hormonal relationships in congenital adrenal hyperplasia.

The temporal relationship between administration of cortisol and serum 17alpha-hydroxyprogesterone was investigated in five patients aged 9-19 years with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. There was marked variability in the 17alpha-hydroxyprogesterone response (determined hourly for 24 h) of individual patients to administration of cortisol. Mean concentration was less than 0.030 micronmol/l in one patient but 0.519 micronmol/l in another. Levels were higher in all patients while off treatment, and were greatest in those with salt-losing adrenal hyperplasia. Growth hormone secretion was not suppressed by treatment with cortisol. Withdrawal of cortisol for 3 days resulted in a significant decrease in the mean serum FSH/LH ratio and a rise in serum testosterone in all subjects. Episodic release of gonadotrophins persisted in the adolescent patients.

Intravenous metyrapone testing. Evaluation of growth hormone and adrenocorticotrophic hormone in children.

An intravenous metyrapone tartrate test was performed on 26 children to assess growth hormone (GH) reserve and pituitary-adrenal axis. Results were compared to the response evoked by an estrogen-primed arginine-insulin tolerance test (ATT/ITT). Administration of metyrapone intravenously proved to be a reliable means of evaluating pituitary-adrenal function. However, a normal serum GH concentration (greater than or equal to 7 ng/ml) during the test occurred in only nine of 18 children who had an adequate response to the ATT/ITT, and in three of these, the peak GH level occurred at the start of the infusion. Therefore, this procedure does not appear to be a satisfactory test for GH reserve in children. Further, the discrepancy between time of the peak serum concentrations of compound S and GH following intravenous administration of metyrapone does not support the contention that the rise of GH level during stress is secondary to release of adrenocorticotrophic hormone.