Tumor recurrence and hypertension persistence after successful pheochromocytoma operation

Pheochromocytoma is a catecholamine-secreting tumor and a rare cause of hypertension that is usually curable. However, pheochromocytoma may recur as a benign or malignant tumor, and hypertension may persist after successful surgical intervention. The frequency of and risk indicators for tumor recurrence and hypertension persistence after successful surgical intervention have not been adequately studied. We determined tumoral and blood pressure outcome in 129 patients followed-up from initial pheochromocytoma resection to death or to 1994 (796 patient-years). We assessed several candidate indicators for their predictive value for the risk of tumor recurrence or hypertension persistence. Recurrence was defined as the reappearance of disease after normalization of biochemical tests. Pheochromocytoma caused death or persistent or recurrent disease in 28 patients. Of the 114 with benign tumors at initial operation, pheochromocytoma recurred as a benign or malignant tumor 17 to 194 months after initial operation in 16 cases. Kaplan-Meier estimates of pheochromocytoma-free survival were 92% and 80% at 5 and 10 years, respectively. In the 98 living patients without recurrence, Kaplan-Meier estimates of hypertension-free survival were 74% and 45% at 5 and 10 years. In the Cox model, familial pheochromocytoma and a low ratio of plasma epinephrine to total catecholamines were independently associated with recurrence. Familial hypertension and age were similarly associated with hypertension persistence. After surgery for pheochromocytoma, patients should be followed-up indefinitely, especially those with familial tumors or a low epinephrine secretion. Pheochromocytoma should not unreservedly be considered a surgically remediable cause of hypertension.     

Bioassay of an endothelium-derived hyperpolarizing factor from bovine coronary arteries: role of a cytochrome P450 metabolite

An endothelium-derived hyperpolarizing factor (EDHF) mediates a part of the vasodilatory action of bradykinin. A bioassay method was developed to investigate the properties of EDHF on bovine coronary arterial smooth muscle cells. Cannulated bovine coronary arteries with an intact endothelium that were treated with indomethacin and NG-nitro-L-arginine methyl ester served as the EDHF donor. The effect of the donor vessel perfusate was examined on a 240 pS single-channel calcium (Ca2+)-activated potassium (K+) current (KCa) and resting membrane potential in recipient coronary arterial smooth muscle cells. The open state probability (NPo) of the channel averaged 0.011 +/- 0.003 during basal perfusate flow. After stimulation of the donor vessels with bradykinin (10(-10)-10(-6) M), the perfusate induced a 1.2- to 5-fold increase in the NPo (n = 7, p < 0.001). This increase in channel activity was attenuated by either removing the endothelium of the donor arterial segment or upon inhibition of cytochrome P450 in the donor arterial segment with the combination of 17-octadecynoic acid and miconazole. The resting cell membrane averaged -60 +/- 2 mV, and hyperpolarized to -69 +/- 1.5 mV (n = 6, p < 0.05) in response to the perfusate following stimulation of the donor vessel with bradykinin. Addition of 14, 15-epoxyeicosatrienoic acid mimicked the effects of the perfusate and increased the NPo of the KCa channel from 0.01 +/- 0.001 to 0.05 +/- 0.001. These findings suggest that bradykinin stimulates the release of a transferable endothelial factor that activates KCa channels and hyperpolarizes coronary arterial smooth muscle cell membranes. These findings support the hypothesis that coronary arteries release an EDHF which is a cytochrome P450 metabolite of arachidonic acid.     

TNF-induced enterocyte apoptosis in mice is mediated by the TNF receptor 1 and does not require p53

Injection of recombinant mouse TNF into mice is known to induce a shrinkage of the duodenal villi, which becomes evident 30-90 min later and is associated with a detachment of enterocytes in the lumen. These cells can be collected by lavage and are all apoptotic, i.e. hypodiploid as seen by flow cytometric analysis. Thus the count of detached cells was used as an evaluation of the TNF-induced cell loss and apoptosis in the mucosa. TNF injection induced a cell loss of similar magnitude in wild-type (+/+) or in mice lacking the TNF receptor (TNFR)2 (p75, TNFR2-/-), while mice lacking the TNFR1 (p55, TNFR1-/-) were completely resistant to this effect. TNF increased the expression of p53 tumor suppressor gene in the enterocytes from the crypts but not from the villi, as seen by Western blots and histochemistry. TNF increased the expression of p53 in both TNFR2-/- and TNFR1-/- mice. Furthermore, enterocyte cell loss was not attenuated in p53-/- mice. The results indicate that TNF, acting on its receptor 1, induces an apoptotic detachment of the enterocytes from the tip of the villi (i.e. the old enterocytes), while in the enterocytes from the crypts (the young enterocytes) TNF increases, via either TNFR1 or TNFR2, the expression of p53, without inducing apoptosis.     

Cyclooxygenases and the central nervous system

Prostaglandins (PGs) were first described in the brain by Samuelsson over 30 years ago (Samuelsson, 1964). Since then a large number of studies have shown that PGs are formed in regions of the brain and spinal cord in response to a variety of stimuli. The recent identification of two forms of cyclooxygenase (COX; Kujubu et al., 1991; Xie et al., 1991; Smith and DeWitt, 1996), both of which are expressed in the brain, along with superior tools for mapping COX distribution, has spurred a resurgence of interest in the role of PGs in the central nervous system (CNS). In this review we will describe new data in this area, focusing on the distribution and potential role of the COX isoforms in brain function and disease.     

Biological role of tyrosinase related protein and its biosynthesis and transport from TGN to stage I melanosome, late endosome, through gene transfection study

OBJECTIVES: To examine the use of tomography for dental implant planning. METHODS: A questionnaire was sent to oral radiology clinics in Sweden and to implantology clinics in different parts of the world with questions on selection criteria and techniques for, and frequency of, pre-implant tomography. Differences between mean values were assessed by t-test. A new method developed by the Swedish Radiation Protection Institute was used to assess radiation absorbed dose from CT. RESULTS: Tomography was used by 93.4% of the clinics, but there was marked variation both between and within different clinical situations. It was performed in all cases by 21% and the majority used it for the evaluation of the maxilla, the posterior mandible and in single implant cases. Small clinics (< 100 patients per year) used tomography frequently and clinics in Sweden significantly more often than those in other countries. The majority had changed their policy recently, using tomography more often. CT was used by 73% of respondents, mainly the small clinics. The majority of the large clinics (> 500 patients per year) used conventional tomography. The mean absorbed dose for CT scanning protocols was 65 mGy. The variation within and between different makes of CT was considerable. CONCLUSIONS: There are large variations in frequency of use of both conventional and computed tomography for dental implant planning by different clinics who also vary in the indications for their choice. A substantial factor influencing the technique chosen was its availability rather than clinical need.     

The first ever radial artery as a conduit in femoro-popliteal bypass: a case report

We report a 4-year-old boy who presented with Guillain-Barré Syndrome 11 days after the onset of erythema infectiosum. The illness resolved without gamma globulin therapy.     

Structural modification of fibroblast growth factor-binding heparan sulfate at a determinative stage of neural development

Heparan sulfate (HS) glycosaminoglycans are essential modulators of fibroblast growth factor (FGF) activity and appear to act by coupling particular forms of FGF to appropriate FGF receptors. During neural development, one particular HS proteoglycan is able to rapidly switch its potentiating activity from FGF-2, as neural precursor cell proliferation occurs, to FGF-1, as neuronal differentiation occurs. Using various analytical techniques, including chemical and enzymatic cleavage, low pressure chromatography, and strong anion-exchange high performance liquid chromatography, we have analyzed the different HSs expressed during these crucial developmental stages. There are distinct alterations in patterns of 6-O-sulfation, total chain length, and the number of sulfated domains of the HS from the more mature embryonic brain. These changes correlate with a switch in the ability of the HS to potentiate the actions of FGF-1 in triggering cell differentiation. It thus appears that each HS pool is designed to function in the modulation of an intricate interaction with a specific growth factor and its cognate receptor, and suggests tightly regulated expression of specific, bioactive disaccharide sequences. The data can be used to construct a simple model of controlled variations in HS chain structure which have functional consequences at a crucial stage of neuronal maturation.     

Effect of laminate stacking sequence on the high frequency fatigue behavior of SCS-6 fiber-reinforced Si3N4 matrix composites

In many potential applications, continuous fiber-reinforced ceramic matrix composites (CFCMCs) will encounter cyclic fatigue loadings at high frequencies (25 Hz or higher). While most of the work in the area of fatigue of CFCMCs has concentrated on low frequency behavior, high frequency behavior is equally important. In CFCMCs, stress-strain hysteresis occurs during fatigue and is associated with energy dissipation in the composite. In addition to this, the repeated friction and sliding between fiber and matrix are responsible for a substantial temperature rise at the fiber/matrix interface. In this study, [0/90] and [±45] SCS-6 (silicon carbide)/Si₃N₄ composites made by hot pressing were investigated under high frequency fatigue loadings. The angle-ply laminate showed the same extent of heating as cross-ply laminates, but at much lower stress levels. Frictional heating was caused by sliding at the fiber/matrix interface. Temperature rise due to heat generation in the specimens correlated very well with damage in modulus as a function of fatigue cycles in the composites. Matrix microcracking was more predominant in the angle ply than in the cross-ply composite, due to the much lower stiffness of the angle-ply composite in the longitudinal loading direction.     

Do people exercise less than they think?

Physical activity is important for health. Physical inactivity is an independent risk factor for disease and speeds up aging. People say in health surveys that they exercise more than they did before. This does not conform with two important facts: Over the last 20 years people have reduced their calorie intake, but their weight is increasing. The only possible explanation is that they exercise less than before, probably because their daily life requires less and less physical activity. We believe this to be a serious health problem, and support the most recent recommendation: A daily walk for 30 minutes.