Respiratory failure is the leading cause of death in the neonatal period. The anatomic and functional basis for this, particularly in full-term infants, most often is persistent pulmonary hypertension of the neonate (PPHN). This condition is reversible but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Recent technologic advances have expanded the scope of therapy available for PPHN, resulting in increasing therapeutic success for these critically ill infants. This article reviews the anatomic and functional anomalies of PPHN, as well as the methods of diagnosis and discusses current treatment.

The question of whether chrysotile asbestos ever causes mesothelioma in man has become a major public and occupational health issue. Review of the literature suggests that only 53 acceptable cases of chrysotile-induced mesothelioma have ever been reported; of these, 41 cases have occurred in individuals exposed to chrysotile mine dust, all of it naturally contaminated with tremolite. Ten cases have occurred in secondary industry workers, but here the suspicion of amosite or crocidolite contamination is high. Analysis of lung asbestos content indicates that induction of mesothelioma by chrysotile requires, on average, as great a lung fiber burden as induction of asbestosis by chrysotile, whereas amphibole (amosite or crocidolite)-induced mesotheliomas appear at a several hundred-fold smaller lung burden. Tremolite alone has definitely produced mesothelioma in man, particularly when exposure has been to long, high aspect ratio, fibers. Analysis of tremolite:chrysotile fiber ratios in human lung suggests that some, but not all tremolite is removed in milling chrysotile ores. The low incidence of mesothelioma in secondary chrysotile users may reflect the small amount of tremolite left in the product. These observations indicate that although chrysotile asbestos can produce mesothelioma in man, the total number of such cases is small and the required doses extremely large. The data are consistent with the idea that mesotheliomas seen in chrysotile miners and some secondary industry workers are produced by the tremolite contained in the chrysotile ore, but that the short length and low aspect ratio of the tremolite make its carcinogenicity quite low. However, these data are very indirect, and a role for the chrysotile fiber itself is still possible.

The multifaceted nature of smoking includes its physiologic, social, and psychologic dimensions and its career features. It develops over time, through phases such as experimentation or conditioning. It also is given up over time, often after several unsuccessful attempts. Several repetitions of a sequence of considering cessation, attempting to quit, and relapsing are likely to precede permanent cessation. Those who are not ready to commit themselves to quitting may be reached by low-key information more than by too forceful exhortation. Those who are ready to quit may select from among a range of approaches, including group clinics, "self-help" manuals, and physician counseling. Maintenance requires as much attention as does cessation. Cooperation from those around the quitter, reminders to use skills for coping with stressors or temptations, and continued encouragement from the physician may all encourage long-term abstinence. Owing to the multifaceted nature of smoking and quitting and the multiple approaches to cessation and its maintenance, the physician may best be viewed as a catalyst for nonsmoking. If appropriate to his or her practice, this may include extended patient counseling, but those unable to provide this may still make great contributions through brief information on why it is important to quit, encouragement to do so, timely referral to other staff or to materials and programs available in the community, and continued expression of interest in the patient's efforts and/or success. All these may catalyze quitting without demanding excessive time or skills beyond those commonly employed by the physician. In catalyzing nonsmoking, the physician can also be an effective proponent of community or voluntary agency programs as well as institutional and governmental policies to limit smoking in health care facilities and public places. The American College of Chest Physicians' policy encouraging nonsmoking among its Fellows and in their offices is an excellent example of this catalyst role.

Supraventricular tachyarrhythmias are common and treatment is based on the frequency and hemodynamic severity caused by these arrhythmias. Empiric therapy with currently available medications often satisfactorily controls symptomatic arrhythmias. Nonpharmocologic therapy with permanent antitachycardia pacemakers, percutaneous catheter ablation or surgery can be effective for selected patients with medically refractory supraventricular tachyarrhythmias after thorough electrophysiologic evaluation. In selected patients with life-threatening supraventricular tachyarrhythmias due to the WPW syndrome, surgical ablation is the therapy of choice.

Esmolol is a new intravenous beta-adrenergic blocker with an ultrashort (nine-minute) elimination half-life, which has been studied predominantly for control of supraventricular tachycardia and management of certain types of hypertension. Clinical studies indicate that the efficacy of esmolol is equivalent to that of propranolol and verapamil for control of supraventricular tachycardia and to sodium nitroferricyanide (sodium nitroprusside) for control of postoperative hypertension. Esmolol also has been shown to control heart rate and blood pressure during episodes of acute myocardial ischemia. Cardioselectivity is similar to that of metoprolol, and the ability to titrate the effect of esmolol may provide additional assurance that beta-adrenergic blockade will remain within the cardioselective range. The most commonly observed adverse effect seen in clinical trials was asymptomatic hypotension. Hypotension may be minimized by titrating to the minimum effective dose and is readily reversed within 10 to 30 minutes of discontinuing the infusion of esmolol. These unique features represent advantages of great potential merit in critical care medicine.

The application of HBO to the therapy of various human diseases developed over a 300 year period. Like most of medicine, the basis of these applications was and continues to be pragmatic in nature, and involves uncritical and untested judgments. The possibility of risks has been understated and possible benefits have been overstated. Individual physicians offering HBO and organized groups, such as the Undersea Medical Society, advocating its use may well be highly motivated, well meaning, and sincerely convinced that HBO is an important therapeutic approach. It may be that, buried among the host of indications, will be some disorders for which HBO is uniquely and highly effective. If so, the present nonsystem for evaluating responses to HBO will require modification, so that these potentially valuable additions to therapeutics are not lost. Because of its almost global application to a wide variety of diseases, HBO therapy lends itself easily to medical adventurism (therapy in search of a disease) and economic exploitation. If there is some patient benefit to come from the experience of the last 300 years, changes in approach, initiated by baromedical devotees or by medicine generally, or resulting from pressures outside of medicine, will be required.

Abnormal mucociliary transport is improvement by the action of theophylline, and this effect can be attributed to several mechanisms. The drug may directly and indirectly mediate the increase in the secretory output of bronchial glands, and this effect is enhanced by the vagal gastropulmonary reflex which is stimulated by the irritant action of theophylline on the stomach. Theophylline can increase the transepithelial secretion of fluid into the respiratory tract lumen by stimulating the chloride pump which is controlled by cyclic AMP. Ciliary motility is stimulated by theophylline; most of this effect is confined to the proximal part of the respiratory tree. However, much of the improvement in mucociliary clearance may be a consequence of the bronchodilation induced by theophylline, since the improved airway patency is generally a prerequisite for enhanced mucokinesis. Nevertheless, the multiple sites of action of theophylline in the respiratory tract suggests that this drug should be considered to be of significant value in any disorder characterized by mucostasis.

One of the important modes of action of theophylline in asthma and chronic obstructive airway disease may be the inhibition of airway inflammation. This hypothesis is based on in vitro and in vivo studies demonstrating that theophylline at therapeutic concentrations has an inhibitory activity on airway inflammation induced by allergic and nonallergic stimuli. Indirect evidence suggests that airway inflammation is an important determinant in the long-term outcome of chronic obstructive airway disease. The effect of theophylline on the long-term evolution of chronic obstructive lung disease remains to be proven.

Recent investigations have shown that theophylline improves diaphragmatic contractility of the respiratory muscles in isolated muscle preparations in animals and in normal human subjects. It has also been demonstrated that theophylline can reverse diaphragmatic fatigue and prevent fatigue of the diaphragm when given prophylactically. These effects have also been demonstrated in patients with severe chronic obstructive pulmonary disease, all of whom retained CO2 (PaCO2 53 +/- 3 mm Hg) and had hypoxia (PaO2 57 +/- 8 mm Hg). Theophylline, which increases respiratory muscle strength and delays the onset of diaphragmatic fatigue therefore could be a very useful agent in the treatment of patients with chronic airway obstruction.