Nitric oxide synthase expression in the medullary respiratory related nuclei and its involvement in CO-mediated central respiratory effects in neonatal rats

The present study was conducted in order to observe the potential participation of the nitric oxide synthase-NO pathway in CO-mediated regulation of respiration of neonatal rats. An immunofluorescent histochemical technique was used to examine the existence of the neuronal nitric oxide synthase, a key enzyme of synthesizing NO, in medullary respiratory nuclei. The rhythmic respiratory-like discharges of hypoglossal rootlets of medullary slices were recorded to test the role of the nitric oxide synthase in CO-mediated respiratory effects. We observed neuronal nitric oxide synthase expressed in the medullary respiratory nuclei in conjunction with CO lengthened expiratory duration, decreased respiratory frequency, and increased inspiratory amplitude. These CO-mediated respiratory effects could be partially eliminated by prior treatment of the slices with Nω-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase. The results suggest that nitric oxide synthase-NO pathway might be involved in the CO-mediated central regulation of respiration at the level of medulla oblongata in neonatal rats.     

Pacemaker management for acute onset of heart block in childhood

Four children aged 2 to 15 years are described who had Stokes-Adams syndrome as the primary cardiac manifestation of complete heart block. All had mild, nonspecific antecedent symptoms without signs of congestive heart failure. Viral neutralizing antibody titers (coxsackievirus B1 and B2) rose significantly in two patients. Electrocardiography demonstrated complete heart block associated with one or more of the following: right bundle branch block, left anterior hemiblock, left bundle branch block, intraventricular conduction delay, and ventricular standstill. In addition, second-degree heart block was seen during the initial or resolving phases of illness. To prevent further life-threatening episodes of Stokes-Adams syndrome, temporary transvenous pacemakers were placed. Two patients with persisting complete heart block required permanent pacemakers. At last examination, the remaining two patients had sinus rhythm and normal conduction. Nonsurgical acquired complete heart block is unusual in childhood, and may be the only manifestation of myocarditis. Extreme bradycardia, which causes syncope, requires immediate temporary cardiac pacing; if the bradycardia persists, a permanent pacemaker should be implanted.     

Intercalation of imidazoacridinones to DNA and its relevance to cytotoxic and antitumor activity

Imidazoacridinones (IA) are a class of antitumor agents which includes C-1311, an interesting drug in clinical trials. This study investigated the mechanism of IA binding to DNA for a series of 13 analogs that differ in their cytotoxic potency. Using C-1311 as a model compound, crystallographic, spectroscopic and biochemical techniques were employed to characterize drug-DNA interactions. X-ray crystallographic analysis revealed a planar structure of imidazoacridinone core that is capable of intercalative DNA binding. Accordingly, C-1311 binding to DNA followed 'classical' pattern observed for intercalation, as proved by the DNA topoisomerase I-unwinding experiments, with relatively weak binding affinity (K(i)=1.2 x 10(5)M(-1)), and the binding site size of 2.4 bp. Other IA also bound to DNA with the binding affinity in the range of 10(5)M(-1) and binding site size of 2-3 bp, suggesting a prevalence of the intercalative mechanism, similar to C-1311. Considerable DNA binding affinity was displayed by all the highly cytotoxic derivatives. However, none of the analyzed drug-DNA binding parameters was significantly correlated with IA biological activities such as cell growth, DNA and RNA synthesis inhibition, or tumor growth inhibition, which suggests that the IA ability to non-covalently bind to DNA is not crucial for their biological activity. These results show that the ability to intercalate into DNA is a prominent attribute of IA, although factors other than intercalative binding seem to be required for the biological activities of IA drugs.     

Development and evaluation of a placebo for studies of operant behavioral intervention

The role of credible placebo conditions in operant intervention research is reviewed. Three studies are presented which were designed to help develop such a placebo condition and then to evaluate its credibility. The results of the studies underscore the necessity for evaluating a placebo condition before employing it in the actual intervention study. Data are offered suggesting that a credible placebo for behavioral treatment of hyperactive children can be developed for use in teacher consultation studies. The data also suggest, however, that credibility ratings are influenced by the manner in which the evaluations are undertaken. The nature of the concept of credibility is also briefly discussed.     

Patterns of perception of health in cardiac patients

Thirty-seven patients hospitalized for cardiac disorders were classified by cluster analysis in four groups based on their patterns of perception of health during the first year of recovery. Striking differences were found in the four patterns obtained. The groups were compared for variables of demographic background, physical health, and psychological state. Significant differences were found between clusters in pre- and post-hospitalization employment, alcoholism, state anxiety in the CCU and ICU, and number of days in CCU. No differences were found for measures of physical health.     

Therapeutic problems arising from the use of the intravenous route for drug administration.

The kinetics of drug delivery were studied under conditions of varying iv flow rates and varying sites of drug administration into an iv system. The iv sites and rates were selected on the basis of questionnaire data obtained from nursing personnel. The rate of drug delivery from the iv system was dependent upon the iv flow rate and site of injection of the drug into the iv system. Under conditions of slow iv flow rates (3 ml/hour) there was the expected time delay required for the drug to begin to be infused but an unanticipated protracted time required for actual completion of the drug infusion. Calculation of theoretical drug blood levels based on the results of these iv studies revealed very different blood levels of drug at respective times, including different peak concentrations, depending on the iv flow rate and site at which the drug was injected into the system. Failure to appreciate the effects of slow iv rates and distal iv injection sites on actual rates of drug administration can adversely affect pharmacokinetic decisions and conceivably influence therapeutic success or failure.     

Indications, complications and results with silicone stents

Fifty-two patients with complicated lacrimal problems were treated with silicone stents. Our overall success rate, judging from a minimum 6-month follow-up, was 40% in these complicated cases, accepting only positive dye tests as our criteria for success. We divided these cases into six groups with successes ranging from 0--68%. Twenty-nine percent of patients had complications related to their stents. While silicone stents are probably the most important recent advance in lacrimal surgery, one must be aware of their indications, limitations and complications.