FGF4 dissociates anti-tumorigenic from differentiation signals of retinoic acid in human embryonal carcinomas.

A subset of male germ cell cancers presenting with advanced stage abundantly express the fibroblast growth factor-4 (FGF4). FGF4 expression is restricted in vitro to undifferentiated embryonal carcinomas (ECs). During induced differentiation, FGF4 expression is repressed in maturation sensitive but not resistant human ECs, suggesting FGF4 plays an important role in malignant growth or differentiation of ECs. To explore these FGF4 signals in male germ cell cancers, the multipotent human EC NTERA-2 clone D1 (NT2/D1) cell line was studied. All-trans-retinoic acid (RA)-treatment of these cells induces a neuronal phenotype and represses tumorigenicity and FGF4 expression. In contrast, RA-treatment of retinoid resistant lines derived from NT2/D1 cells failed to repress FGF4 expression. This implicated FGF4 directly in regulating human EC growth or differentiation. To evaluate further this FGF4 role, FGF4 was constitutively over-expressed in NT2/D1 cells using a CMV-driven expression vector containing the neomycin resistance gene. Three stable transfectants expressing exogenous FGF4 were studied as was a control transfectant only expressing the neomycin resistance gene. RA-treatment repressed endogenous but not exogenous FGF4 expression. RA-treatment of these transfectants induced morphologic and immunophenotypic maturation, changes in RA-regulated genes, and a G1 cell cycle arrest in a manner similar to parental NT2/D1 cells. This indicated FGF4 over-expression did not block RA-mediated differentiation. As expected, RA-treatment repressed tumorigenicity of the control transfectant after subcutaneous injection into athymic mice. Despite RA-treatment, this repressed tumorigenicity was overcome in all the transfectants over-expressing FGF4. The histopathology and neovascularization did not appreciably differ between xenograft tumors derived from FGF4 over-expressing versus control transfectants. FGF4 expression studies were extended to patient-derived germ cell tumors using total cellular RNA Northern analysis and an immunohistochemical assay developed to detect FGF4 protein expression. Germ cell tumors with EC components were significantly more likely to express FGF4 mRNA (P < or = 0.0179) than other examined germ cell tumors without EC components. Immunohistochemical results from 43 germ cell tumors demonstrated increased FGF4 expression especially in non-seminomas having EC components. Thus, FGF4 promotes directly malignant growth of cultured ECs, overcomes the antitumorigenic actions of RA, and is selectively expressed in specific histopathologic subsets of germ cell tumors. Taken together, these findings indicate how differentiation and anti-tumorigenic retinoic acid signals can be dissociated in germ cell cancer.

Disparity of reperfusion arrhythmias after reversible myocardial ischemia in open chest and conscious dogs.

Myocardial reperfusion after brief, reversible ischemia is frequently associated with malignant arrhythmias in experimental animals. These observations have been extrapolated to humans despite being restricted to anesthetized, open chest preparations. No data are available regarding the incidence of reperfusion arrhythmias after reversible (less than 20 minutes) ischemia in the conscious state. Thus, reperfusion arrhythmias after a 15 minute occlusion of the left anterior descending coronary artery were compared in 24 open chest dogs (17 anesthetized with pentobarbital and 7 with chloralose plus urethane) and 25 conscious, unsedated, trained dogs. The incidence of all rhythm disorders (single premature ventricular complexes, pairs, ventricular tachycardia and fibrillation) was markedly and significantly lower in conscious than in either pentobarbital- or chloralose-anesthetized dogs. The disparity was not accounted for by differences in coronary collateral flow, coronary reactive hyperemia or occluded bed size. The conscious animals, however, exhibited lower heart rates and arterial pressures during reperfusion than did the open chest dogs, suggesting a lower level of adrenergic stimulation, which might have contributed to the reduced incidence of reperfusion arrhythmias. Coronary reperfusion after 15 minutes of occlusion is unlikely to precipitate ventricular tachyarrhythmias in the conscious, trained dog, even after severe ischemia. The occurrence of these rhythm disorders in anesthetized models may reflect the influence of surgical trauma or excessive adrenergic activity, or both. Reperfusion arrhythmias after reversible ischemia may be considerably less common in the clinical setting than previously postulated on the basis of open chest animal experiments.

N-2-mercaptopropionylglycine improves recovery of myocardial function after reversible regional ischemia.

Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 +/- 0.01 ml/min per g (mean +/- SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 +/- 1.2% of the weight of the left ventricle in control and 29.6 +/- 1.3% in treated animals. Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p less than 0.02), 3 hours (77.1 versus 36.7%, p less than 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p less than 0.05). Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

The St. Jude valve prosthesis: analysis of the clinical results in 815 implants and the need for systemic anticoagulation.

Between July 1979 and December 1984, 785 patients received 815 St. Jude Medical valve prostheses. Valve-related mortality in the follow-up period was due to thromboembolism in seven cases, anticoagulant-related hemorrhage in three and perivalvular leak in two. Freedom from valve-related death or reoperation at 3 years was 96.4% for aortic valve replacement and 98.3% for mitral valve replacement. The overall rate of thromboembolism was 2.6%/patient-year with warfarin, 9.2%/patient-year with antiplatelet medication and 15.6%/patient-year in patients with no anticoagulant therapy. One episode of thrombotic obstruction of a mitral valve, in a patient receiving no anticoagulant therapy, resulted in an occurrence rate of such obstruction of 0.22%/patient-year. Valve replacement with the St. Jude valve produced excellent clinical results, but long-term anticoagulation with warfarin was required to minimize thromboembolic complications. The use of antiplatelet agents alone provided inadequate protection.

Hydrogen peroxide induced impairment of post-ischemic ventricular function is prevented by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide).

OBJECTIVE: Sodium-hydrogen exchange (NHE) activation is a major mechanism of cardiac injury produced by ischemia and reperfusion. In addition, NHE may mediate the direct effects of hydrogen peroxide (H2O2) in normally perfused hearts. The present study was done to determine whether H2O2 at low concentrations producing mild myocardial depression affects post-ischemic recovery of function and to determine the ability of the NHE inhibitor HOE 642 to modulate this effect. METHODS: Isolated Langendorff-perfused rat hearts with a left ventricular balloon inflated to an initial end-diastolic pressure of 5 mmHg were subjected to 90 min of global zero-flow ischemia followed by 60 min reperfusion. In Study 1, hearts were randomized for perfusion with or without H2O2 (20 microM) for 15 min before ischemia and throughout reperfusion. In Study 2, identical experiments were done except that the hearts were pretreated with the NHE inhibitor HOE 642 (5 microM). Function was assessed by determining intraventricular pressures. RESULTS: Recovery of developed pressure in Study 1 after 10 min reperfusion was 60.3 +/- 8% of pre-ischemic values in control hearts whereas this was reduced to 29.9 +/- 10% in hearts treated with H2O2 (P < 0.05). After 60 min of reperfusion recovery of developed pressure was 80.3 +/- 5.2% and 60.7 +/- 7% in control and H2O2-treated hearts, respectively (P < 0.05). Recovery of rates of pressure development (+dP/dt) and relaxation (-dP/dt) paralleled the effects seen with developed pressure. Moreover, these effects were associated with significantly elevated end-diastolic pressure during the last 20 min of reperfusion. In Study 2, HOE 642 completely prevented the deleterious effect of H2O2, both with respect to ventricular recovery and to the elevation in end-diastolic pressure during reperfusion. CONCLUSIONS: Our results show that very low concentrations of H2O2 significantly impair recovery of function in this rat model of myocardial ischemia-reperfusion. Moreover, our results suggest that this effect is likely dependent on NHE activity and can be prevented by treatment with the NHE inhibitor HOE 642.

Sodium-hydrogen exchange inhibitors improve postischemic recovery of function in the perfused rabbit heart.

OBJECTIVE: The aim was to examine the effects of the Na+/H+ exchange inhibitors amiloride and methylisobutyl amiloride (MIA) in buffer perfused rabbit hearts subjected to one hour of normothermic ischaemia (37 degrees C) followed by reperfusion. METHODS: Experiments were carried out in five groups of Langendorff perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both the preischaemic and reperfusion perfusate), (4) amiloride-R and (5) MIA-R (agents added at reperfusion only). Functional evaluation included serial measurement of resting tension, force, rates of ventricular force development and relaxation, and coronary perfusion pressure. Samples of coronary effluent were obtained for creatine kinase assay and hearts were freeze clamped for metabolite assays. RESULTS: Reperfusion resulted in a marked increase in resting tension in group (1) which was statistically significant compared to groups (2) and (3). Groups (2) and (3) also showed significantly improved recovery of ventricular force, rate of force development, and rate of ventricular relaxation. Addition of either agent only during reperfusion failed to produce a significant beneficial effect. There were no significant differences among the groups with respect to postreperfusion creatine kinase release or end reperfusion metabolite levels. CONCLUSION: This study shows for the first time that both of the Na+/H+ exchange inhibitors amiloride and MIA produce improved recovery of ventricular function in rabbit hearts subjected to ischaemia and reperfusion, although the beneficial effect was not obtained with drug administration at the time of reperfusion only.

Beta-adrenergic stimulation reverses postischemic myocardial dysfunction without producing subsequent functional deterioration.

The prolonged myocardial dysfunction observed after reversible ischemia (stunned myocardium) has been postulated to result from an inability of the myocytes to replenish ATP stores. Accordingly, one would expect inotropic stimulation to result in minimal increase in contractile function, or possibly even further deterioration. To test this hypothesis, studies were performed in open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery (LAD) followed by 4 hours of reperfusion. Systolic wall thickening, an index of regional myocardial function, was measured in the LAD-dependent territory with ultrasonic crystals. Thickening fraction was 20.8 +/- 3.0% (mean +/- standard error of the mean) under baseline conditions, decreased to -18.6 +/- 1.6% during LAD occlusion, and was still severely depressed after 3 hours of reperfusion (2.6 +/- 3.4%). Thickening fraction remained stable between 3 and 4 hours of reperfusion in 5 untreated control dogs. In 9 treated dogs, isoproterenol (0.1 microgram/kg/min intravenously for 30 minutes starting 3 hours after reperfusion) increased thickening fraction to values (24.8 +/- 4.5%) that were similar to those at baseline. Thirty minutes after discontinuation of isoproterenol administration, thickening fraction had returned to pre-isoproterenol levels. Thus, reperfused, severely depressed myocardium responds dramatically to beta-adrenergic stimulation without subsequent adverse effects on function in the short-term. These findings imply that the stunned myocardium can generate ATP, and therefore do not support the view that an inability to replenish ATP stores is the cause of postischemic dysfunction. More important, this study suggests that postischemic dysfunction in humans may be effectively reversed with inotropic therapy without short-term deleterious sequelae.

Biventricular function in the adult respiratory distress syndrome.

We examined biventricular function in patients with the adult respiratory distress syndrome (ARDS) by a combination of invasively determined pressures and flows and concomitant radionuclide angiography. Right (RVEF) and left (LVEF) ventricular ejection fractions were measured; right and left ventricular end-diastolic (EDVI) and end-systolic (ESVI) volume indices were calculated from the respective ejection fraction and measured thermodilution stroke volume. With an increase in the outflow pressure load on the right ventricle, measured as the mean pulmonary artery pressure (PAP), the RVEF fell (Y = 66.25 -1.01X; r2 = .42; p less than .001) and both the RVEDVI (y = 13.39 + 3.66X; r2 = .33; p less than .001) and RVESVI (Y = 23.9 + 3.57X; r2 = .41; p less than .001) increased. Progressive increases in the PAP also seemed associated with a change in left ventricular end-diastolic pressure-volume relationships: without pulmonary artery hypertension (PAP less than 20 mm Hg) the mean LVEDVI was 87.2 +/- 31.3 ml/m2 (mean +/- SD) and the mean PCWP was 5.0 +/- 2.8 mm Hg; with a mean PAP exceeding 30 mm Hg, the LVEDVI remained constant (90.4 +/- 26.9 ml/m2) although the PCWP was greater than previous (18.5 +/- 5.7 mm Hg; p less than .01). Analysis of right ventricular peak-systolic pressure end-systolic volume ratios implied a concurrent depression in right ventricular contractility at high levels of PAP. However, right ventricular "pump" function to maintain an adequate left ventricular preload remained unaltered regardless of the presence of pulmonary artery hypertension.

The short-term effects of increasing plasma colloid osmotic pressure in patients with noncardiac pulmonary edema.

We infused hyperoncotic albumin (25 or 50 gm of a 50% solution) into patients with noncardiac pulmonary edema (adult respiratory distress syndrome [ARDS]) to evaluate its effect on the transmicrovascular flux from blood to pulmonary edema fluid of two radiotracers--111In-DTPA (mol wt 504) and 125I-human serum albumin (HSA) (mol wt 69,000). Two groups of patients were studied--one with a modest increase in permeability of the pulmonary alveolocapillary membrane to 125I-HSA (group 1) and another with a large increase in permeability to 125I-HSA (group 2). We used furosemide, when necessary, to minimize the effect of albumin infusion to increase the pulmonary microvascular hydrostatic pressure (Pmv), measured clinically as the pulmonary capillary wedge pressure (PCWP). Therapy significantly increased the mean colloid osmotic pressure (COP) in both groups, but not the mean PCWP or calculated Pmv. Albumin had no significant effect on the mean pulmonary transmicrovascular flux of the radiotracers in either group, despite the increase in COP. In individual patients, a change in the Pmv in response to albumin infusion was directly correlated with the change in flux of 111In-DTPA [group 1: delta In-DTPA (%) = 8.66 + 1.4 delta Pmv (%) r = 0.51, P less than 0.02; group 2: delta In-DTPA (%) = -3.43 + 1.6 delta Pmv (%) r = 0.67, P less than 0.01]. A change in the transmicrovascular flux of I-HSA also correlated with a change in the intravascular Starling forces in both groups. We conclude that albumin infusion in patients with ARDS will not augment the pulmonary transmicrovascular flux of low or high molecular-weight solutes when the effect of albumin to increase the Pmv is minimized; nor, however, does an increase in plasma COP significantly reduce the flux of such solutes.

Effects of isoproterenol on myocardial structure and function in septic rats.

In this study we sought to determine the effect of sepsis on two sequelae of prolonged (24-h) beta-agonist administration, myocardial hypertrophy and catecholamine-induced cardiotoxicity. Sprague-Dawley rats were randomized to cecal ligation and perforation (CLP) or sham study groups and then further randomized to receive isoproterenol (2.4 mg. kg-1. day-1 iv) or placebo treatment. At 24 h, myocardial function was assessed by using the Langendorff isolated-heart technique or the heart processed for plain light microscopy. We found that 1) sepsis reduced contractile function, indicated by a rightward shift in the Starling curve (ANOVA with repeated measures, sepsis effect, P < 0.002); 2) sepsis-induced myocardial depression was reversed by isoproterenol treatment (isoproterenol effect, P < 0.0001); 3) sepsis reduced, but did not block, isoproterenol-induced myocardial hypertrophy (isoproterenol effect, P < 0.0001); 4) sepsis did not protect the heart from catecholamine-induced tissue injury; 5) the septic heart was protected against the effects of ischemiareperfusion (decreased postreperfusion resting tension, ANOVA with repeated measures, P < 0.01), an effect attenuated by isoproterenol treatment (P < 0.005); and 6) sepsis reduced the incidence of sustained asystole or ventricular fibrillation after ischemia-reperfusion (P < 0.05), an effect also attenuated by isoproterenol treatment (P < 0.01). We conclude that, in sepsis, beta-agonists induce changes in myocardial weight and function consistent with acute myocardial hypertrophy. These changes occur at the expense of significant tissue injury and increased sensitivity to ischemia-reperfusion-induced tissue injury.

Improved cardiac function after prolonged hypothermic ischemia with the Na+/H+ exchange inhibitor HOE 694.

BACKGROUND: Na+/H+ exchange represents an important mechanism for pH regulation in the cardiac cell that, however, may paradoxically mediate tissue damage in the reperfused myocardium. We investigated whether inhibition of the exchanger can protect the heart against damage after prolonged hypothermic storage with the use of the selective inhibitor 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694). METHODS: After equilibration, isolated rabbit hearts were arrested with a 3 minute infusion of modified St. Thomas' cardioplegic solution and subsequently maintained in ischemic arrest at 4 degrees C for 12 hours before reperfusion at 37 degrees C for 60 minutes. Left ventricular function and creatine kinase release were measured at intervals throughout reperfusion. High-energy phosphate and adenine nucleotide content were determined in hearts before cardioplegia, at the end of the 12-hour storage period, and at the end of reperfusion. HOE 694 (1 mumol/L) was administered either with cardioplegia and throughout reperfusion (study 1) or selectively with either cardioplegia or reperfusion only (study 2). RESULTS: In study 1, systolic function in untreated hearts recovered to less than 40% of preischemic values and was associated with a greater than 1,000% percent sustained elevation in left ventricular end-diastolic pressure. In contrast, systolic recovery in HOE 694-treated hearts was significantly accelerated and improved to approximately 80%, whereas left ventricular end-diastolic pressure increased to only 300% of baseline. Significant protection also occurred in those hearts in which HOE 694 was administered only at reperfusion while the drug was less effective if given only during cardioplegia. Creatine kinase release was not significantly affected except in study 2, where it was significantly lower after 60 minutes of reperfusion in hearts where HOE 694 was added at the time of reperfusion. Tissue metabolite content was not affected by drug treatment. CONCLUSIONS: This study shows a marked protective effect of the Na+/H+ exchange inhibitor HOE 694 in rabbit hearts subjected to 12 hours of hypothermic ischemia and strongly suggests that antiport inhibitors could play an effective role in myocardial preservation.

Pleuropulmonary morbidity: internal thoracic artery versus saphenous vein graft.

Although use of the internal thoracic artery (ITA) for coronary artery bypass grafting results in superior graft patency and improved patient survival, our initial clinical observations suggested an increased incidence of pleuropulmonary morbidity with its use. One hundred consecutive patients with left ITA grafts were studied prospectively and compared with a consecutive retrospective group of 100 patients undergoing coronary artery bypass grafting with saphenous vein grafts only. Preoperative, postoperative day (POD) 2, POD 6, and postoperative week 8 chest roentgenograms were analyzed for atelectasis and effusion. Postoperative left lower lobe atelectasis was common in both groups on both POD 2 (saphenous vein, 43%, versus ITA, 53%; not significant) and POD 6 (saphenous vein, 40%, versus ITA, 41%; not significant). There was a significantly higher incidence of pleural effusion on POD 6 in the ITA group (84% versus 47%; p less than 0.05) but most of these were small. There was more chest tube drainage (1,413 versus 1,028 mL; p less than 0.01) and a greater need for secondary thoracostomy or thoracentesis (4% versus 0%) in the ITA group. The left pleural space was opened in 67 of the 100 ITA patients but pleurotomy did not appear to influence postoperative morbidity. We conclude that use of the internal thoracic artery for coronary artery bypass grafting results in a small but significant increase in pleuropulmonary morbidity.

Incidental malignancy in internal thoracic artery lymph nodes.

The incidental finding of malignant internal thoracic lymph nodes while mobilizing the internal thoracic artery (ITA) for coronary bypass grafting has not to our knowledge been previously reported. The cases of 3 male patients who underwent surgery between January 1990 and January 1993 and in whom malignant lymph nodes were found in the ITA pedicle are reviewed. One individual was found to have metastatic carcinoma of the breast, whereas the other 2 were discovered to have previously undiagnosed lymphomas. After undergoing further relevant investigation and treatment, all 3 patients remain free of recurrent disease 6.8 to 9.8 years after their original cardiac surgery. Primary or metastatic malignancy may be encountered in the course of ITA mobilization for grafting. Abnormally enlarged internal thoracic lymph nodes should be sent for pathologic examination.

Blunt cardiac trauma: survival after bichamber rupture.

Rupture of cardiac chambers after nonpenetrating blunt thoracic trauma is being recognized with increasing frequency. Despite a high mortality rate, survival after repair of a single-chamber rupture is widely reported. Bichamber cardiac rupture is less frequent, and we report a patient who survived this injury.

Activated neutrophils impair rabbit heart recovery after hypothermic global ischemia.

Cardiopulmonary bypass is known to cause neutrophil activation, and activated neutrophils appear to be of importance in myocardial reperfusion injury. This study examined the effect of a preischemic infusion of activated neutrophils on the recovery of myocardial function after 40 minutes of hypothermic global ischemia. Studies were carried out in three groups of Langendorff-perfused rabbit hearts: control, control (unactivated) neutrophil infusion, and phorbol myristate acetate-activated neutrophil infusion. The activated neutrophil group showed significant deterioration in function during the activated neutrophil infusion. All three groups demonstrated significant depression of function initially after reperfusion, but the two control groups subsequently recovered to baseline levels. The activated neutrophil group, however, showed a persistent significant depression in ventricular force, rate of ventricular tension development, and rate of ventricular relaxation as well as a significant increase in coronary vascular resistance. It is concluded that activated neutrophils depress myocardial function and contribute to impaired recovery of function after global hypothermic ischemia.

Reducing tobacco addiction through tobacco product regulation.

Tobacco product regulation has the potential to help reduce tobacco attributable disease by reducing the toxicity of these products and by reducing the prevalence of tobacco use and addiction.

Activated neutrophils depress myocardial function in the perfused rabbit heart.

OBJECTIVE: To examine the effect of activated neutrophils on myocardial function in the absence of ischemic and/or reperfusion injury. DESIGN: Studies were carried out in five groups of Langendorff perfused rabbit hearts: control; nonactivated rabbit neutrophil infusion; phorbol myristate acetate-activated rabbit neutrophil infusion; nonactivated human neutrophil infusion; and phorbol myristate acetate-activated human neutrophil infusion. RESULTS: Both groups receiving activated neutrophils showed significant deterioration in ventricular force, rate of ventricular force development (dF/dt) and rate of ventricular relaxation (-dF/dt), and significant increases in coronary vascular resistance. Myocardial lipid peroxidation was assessed but there was no significant difference among groups. Myocardial prostacyclin production was significantly increased in hearts receiving the phorbol myristate acetate-activated human neutrophil infusion. CONCLUSION: It is concluded that myocardial perfusion with activated neutrophils results in depression of myocardial function and an increase in coronary vascular resistance even in the absence of ischemic/reperfusion injury.

Anomalous mitral arcade: a rare cause of mitral valve disease in an adult.

Anomalous mitral arcade is a rare congenital abnormality of the mitral valve not previously described in an adult. Familiarity with this anomaly may facilitate interpretation of left ventricular abnormalities detected with echocardiography or contrast ventriculography in patients with evidence of mitral valve disease.

Occupational safety and health: progress toward the 1990 objectives for the nation.

Occupational safety and health is 1 of 15 areas addressed in the Public Health Service's Objectives for the Nation. This area represents 104 million working men and women and the deaths, diseases, and injuries that result from exposures to hazards in their work environment. Characteristics of public health practice are compared with characteristics of occupational safety and health practice. The National Institute for Occupational Safety and Health (NIOSH), created by the Occupational Safety and Health Act, is discussed. NIOSH has developed a list of 10 leading work-related diseases and injuries. The list is headed by occupational lung diseases. Twenty Objectives for the Nation in the area of occupational safety and health are reviewed, and the status of NIOSH efforts toward their attainment is discussed. Five categories of objectives are covered: (a) improved health status, (b) reduced risk factors, (c) improved public and professional awareness, (d) improved service and protection, and (e) improved surveillance and evaluation. The potential for achieving these objectives is discussed, with special attention given to the lack of a data base for monitoring progress. A major conclusion is that surveillance in occupational safety and health needs to be strengthened.

Assessing the effects of 10 percent carbamide peroxide on oral soft tissues.

To examine the effects of a 10 percent carbamide peroxide bleaching gel on the oral soft tissues, the authors conducted a prospective, double-blind, placebo-controlled clinical investigation. Fifty-two patients completed a two-week treatment regimen, applying either a placebo or a 10 percent carbamide peroxide gel in a soft tray for eight hours a day. Clinicians examined the participants' oral soft tissues at baseline and one week, two weeks and six weeks after the first treatment. The examiners recorded the Silness and Löe plaque and gingival indexes, nonmarginal gingival index and nongingival oral mucosal index at each examination. The data collected at these intervals did not indicate that any soft tissue damage had occurred as a result of the bleaching regimen.