Dermatan sulfate released after injury is a potent promoter of fibroblast growth factor-2 function

Proteoglycans have been shown in vitro to bind multiple components of the cellular microenvironment that function during wound healing. To study the composition and function of these molecules when derived from an in vivo source, soluble proteoglycans released into human wound fluid were characterized and evaluated for influence on fibroblast growth factor-2 activity. Immunoblot analysis of wound fluid revealed the presence of syndecan-1, syndecan-4, glypican, decorin, perlecan, and versican. Sulfated glycosaminoglycan concentrations ranged from 15 to 65 microgram/ml, and treatment with chondroitinase B showed that a large proportion of the glycosaminoglycan was dermatan sulfate. The total glycosaminoglycan mixture present in wound fluid supported the ability of fibroblast growth factor-2 to signal cell proliferation. Dermatan sulfate, and not heparan sulfate, was the major contributor to this activity, and dermatan sulfate bound FGF-2 with Kd = 2.48 microM. These data demonstrate that proteoglycans released during wound repair are functionally active and provide the first evidence that dermatan sulfate is a potent mediator of fibroblast growth factor-2 responsiveness.     

Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.     

Emergency medicine: beyond the basics

Medical emergencies can arise in the dental office. Preparedness for these emergencies is predicated on an ability to rapidly recognize a problem and to effectively institute prompt and proper management. In all emergency situations, management is based on implementation of basic life support, as needed. The author describes the appropriate management of two common emergency situations: allergy and chest pain.     

TNF-alpha-induced corticosterone elevation but not serum protein or corticosteroid binding globulin reduction is vagally mediated

OBJECTIVE: Growth deficiency is commonly seen in polytransfused beta-thalassaemia patients, especially in adolescence. It is not completely dependent on the lack of their pubertal growth spurt. GH impairment at different levels (hypothalamic or pituitary) and/or a reduced IGF-1 synthesis have been suggested the main causes of stunted growth in these patients. We evaluated the relationship between GH reserve and growth in short beta-thalassaemia patients. PATIENTS: Twenty-nine short patients (height < -1.8 SDS for chronological age) were divided into two groups (low and normal responders) on the basis of their GH peak during insulin and clonidine tests (< or = and > 20 mU/l, respectively). All but one low responders underwent the GHRH test to exclude the impairment of somatotroph function and in eight of them an IGF-1 generation test was also performed. The two groups were compared with each other with respect to growth (height deficiency, height velocity, bone age and bone delay), haematological characteristics (serum ferritin levels, age at the start both of low (subcutaneous) s.c. infusion of desferrioxamine and of transfusional therapy) and serum IGF-1 and IGF-1 binding protein 3 levels. RESULTS: Thirteen patients (45%) (11 males, two females) were low responders, all but two having serum IGF-1 < 5th centile (< 0.1 centile in 42%); the GHRH test excluded the impairment of somatotroph function in 8/12. Height deficiency, serum ferritin levels, and age at the start of s.c. chelating therapy did not differ in low compared to normal responders. Height was negatively correlated both with the age at the start of s.c. chelating therapy and with serum ferritin levels. CONCLUSION: The reduction of GH reserve, more frequently due to a hypothalamic than to a pituitary dysfunction, is frequent in polytransfused beta-thalassaemia patients, especially in males. The height function is not related to the GH reserve, given the current methods for testing GH reserve. Late start of s.c. chelating therapy as well as haemosiderosis seem to play a role in the height deficiency, but not in GH reserve. Impairment of GH secretory reserve, therefore, cannot be considered the main cause of height deficiency in these patients.     

Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure

OBJECTIVES: We sought to assess the effects of combined oral positive inotropic and beta-blocker therapy in patients with severe heart failure. BACKGROUND: Patients with severe, class IV heart failure who receive standard medical therapy exhibit a 1-year mortality rate >50%. Moreover, such patients generally do not tolerate beta-blockade, a promising new therapy for chronic heart failure. Positive inotropes, including phosphodiesterase inhibitors, are associated with increased mortality when administered over the long term in these patients. The addition of a beta-blocker to positive inotropic therapy might attenuate this adverse effect, although long-term oral inotropic therapy might serve as a bridge to beta-blockade. METHODS: Thirty patients with severe heart failure (left ventricular ejection fraction [LVEF] 17.2+/-1.2%, cardiac index 1.6+/-0.1 liter/min per m2) were treated with the combination of oral enoximone (a phosphodiesterase inhibitor) and oral metoprolol at two institutions. Enoximone was given at a dose of < or = 1 mg/kg body weight three times a day. After clinical stabilization, metoprolol was initiated at 6.25 mg twice a day and slowly titrated up to a target dose of 100 to 200 mg/day. RESULTS: Ninety-six percent of the patients tolerated enoximone, whereas 80% tolerated the addition of metoprolol. The mean duration of combination therapy was 9.4+/-1.8 months. The mean length of follow-up was 20.9+/-3.9 months. Of the 23 patients receiving the combination therapy, 48% were weaned off enoximone over the long term. The LVEF increased significantly, from 17.7+/-1.6% to 27.6+/-3.4% (p=0.01), whereas the New York Heart Association functional class improved from 4+/-0 to 2.8+/-0.1 (p=0.0001). The number of hospital admissions tended to decrease during therapy (p=0.06). The estimated probability of survival at 1 year was 81+/-9%. Heart transplantation was performed successfully in nine patients (30%). CONCLUSIONS: Combination therapy with a positive inotrope and a beta-blocker appears to be useful in the treatment of severe, class IV heart failure. It may be used as a palliative measure when transplantation is not an option or as a bridge to heart transplantation. Further study of this form of combined therapy is warranted.     

Unilateral phrenic nerve paralysis from cutting down a Christmas tree

Stretch injury to the phrenic nerve is an unusual cause of unilateral diaphragmatic paralysis. In this case the injury occurred while the patient was lying on the ground and cutting down a Christmas tree with a hand saw.     

Intraluminal duodenal diverticulum presenting as obstructive chronic pancreatitis

The presence of angiotensin II receptors was found on cells of three colorectal carcinoma cell lines. The binding assays with 125I-labelled angiotensin II and ligands specific for angiotensin AT1 or AT2 receptors showed that angiotensin receptors on colorectal cancer cells are mostly of the AT2 type. The binding capacity of tumor cells was not significantly changed by butyrate-induced differentiation.     

Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia

OBJECTIVE: This study aims to evaluate the risk of esophagectomy in the elderly compared with younger patients and to determine whether results of esophagectomy in the elderly have improved in recent years. SUMMARY BACKGROUND DATA: An increased life expectancy has led to more elderly patients presenting with carcinoma of the esophagus in recent years. Esophagectomy for carcinoma of the esophagus is associated with significant morbidity and mortality, and advanced age is often considered a relative contraindication to esophagectomy despite advances in modern surgical practice. METHODS: The perioperative outcome and long-term survival of 167 elderly patients (70 years or more) with esophagectomy for carcinoma of the esophagus were compared with findings in 570 younger patients with esophagectomy in the period 1982 to 1996. Changes in perioperative outcome and survival between 1982 to 1989 and 1990 to 1996 were separately analyzed. RESULTS: The resection rate in the elderly was 48% (167/345), lower than the 65% (570/874) resection rate in younger patients (p < 0.001). There were significantly more preoperative risk factors and postoperative medical complications in the elderly, but no significant differences were observed in surgical complications. The 30-day mortality rate was higher in the elderly (7.2%) than in younger patients (3.0%) (p = 0.02), but the hospital mortality rate was not significantly different in the elderly (18.0%) and younger age groups (14.4%) (p = 0.27). The long-term survival after curative resection in elderly patients was worse than younger patients (p = 0.01). However, when deaths from unrelated medical conditions were excluded from analysis, survival was similar between the two age groups (p = 0.23). A comparison of data for the periods 1982 to 1989 and 1990 to 1996 revealed that the resection rate had increased from 44% to 54% in the elderly, with significantly fewer postoperative complications and lower 30-day and hospital mortality rates. Long-term survival has also improved, although this has not reached a statistically significant level. CONCLUSIONS: With current surgical management, esophagectomy for carcinoma of the esophagus can be carried out with acceptable risk in the elderly, but intensive perioperative support is required. The improved results of esophagectomy in the elderly in recent years are attributed to increased experience and better perioperative management. Long-term survival was similar to that of younger patients, excluding deaths caused by unrelated medical conditions.     

The correlation between skin electrical conductance and the score of qi vacuity

In traditional Chinese medicine, the syndrome of qi vacuity means that the patient's body has a low level of energy to react to stress. Recently, we used a score, the QV score, by scaling the severity of symptoms and signs of qi vacuity in patients with tiredness. The aim of this study was to investigate the relationship between QV score and skin electrical conductance in patients with tiredness. One hundred and forty-three healthy controls and 103 patients with tiredness were involved. Each subject received a weak electrical stimulation with constant voltage (1.75 volt), and conductance was measured between two different limbs. The mean value of skin conductance among four limbs was calculated and expressed by a special unit, namely Chin. The correlation between the skin conductance and QV score was analyzed by a linear regression analysis. The results showed that skin electrical conductance of healthy controls was negatively correlated with age (r-coefficient = -0.51, P = 0.000). The skin conductance of patients with tiredness was significantly lower than that of healthy controls with matching age (P = 0.000 by Student's t-test). Moreover, there was a positive correlation between the decrease of skin conductance and the QV score in patients with tiredness (r-coefficient = +0.68, P = 0.000). These results suggest that a decrease in skin electrical conductance may be closely related to the severity of qi vacuity. The skin conductance test is a simple, reliable, and quantitative method for detection of syndrome of qi vacuity.