Nicotine alters some of cocaine's subjective effects in the absence of physiological or pharmacokinetic changes.

Tobacco smoking and cocaine use often co-occurs and the frequency of smoking has been positively correlated with the likelihood of cocaine use. In addition, nicotine pretreatment has been shown to increase the rate of cocaine self-administration in rats and to enhance cue-induced cocaine craving in humans. The present study was conducted to investigate whether nicotine pretreatment via a transdermal patch alters the behavioral, physiological, and pharmacokinetic effects of an acute dose of cocaine in nondependent human volunteers. Seven male tobacco smokers who used cocaine occasionally provided informed consent and participated in this placebo-controlled, four-visit study. Following pretreatment with a transdermal nicotine patch (placebo, 14 mg), subjects were challenged with an acute dose of intranasal cocaine (placebo, 0.9 mg/kg). Nicotine pretreatment attenuated cocaine-induced increases in reports of "high" and "stimulated" and increased the latency to detect cocaine effects and cocaine-induced euphoria. Nicotine did not alter cocaine's effects on heart rate, skin temperature, and blood pressure or plasma cocaine, benzoylecgonine (BE), or ecgonine methylester (EME) concentrations. Our findings indicate that nicotine pretreatment alters some of the positive subjective effects of cocaine in humans without affecting cocaine's effects on physiologic responses or pharmacokinetic profiles.     

Identification of members of the Burkholderia cepacia complex by species-specific PCR

Definitive identification of the species in the Burkholderia cepacia complex by routine clinical microbiology methods is difficult. Phenotypic tests to identify B. multivorans and B. vietnamiensis have been established; more recent work indicates B. stabilis may also be identified by growth characteristics and biochemical tests. However, attempts to identify genomovars I and III have, thus far, proved unsuccessful. Previously, we demonstrated the utility of two primer pairs, directed to the rRNA operon, to specifically identify the B. cepacia complex in a PCR. One of these primer pairs, G1-G2, only amplified a DNA fragment from genomovars I and III and B. stabilis in a PCR with genomic DNA isolated from prototypical strains representing the five genomovars. Sequence analysis of the rRNA operon for all the genomovars indicated that this primer pair targeted a region shared by these isolates. Further analysis revealed a region of heterogeneity between genomovar III and B. stabilis internal to the amplified product of G1-G2. Primers designed to target this region were tested with prototypical strains following an initial amplification with the G1-G2 primer pair. New primers specific for the prototypical genomovar III and B. stabilis were designated SPR3 and SPR4, respectively. Analysis of 93 isolates representing 18 genomovar I, 13 B. multivorans, 36 genomovar III, 11 B. stabilis, and 15 B. vietnamiensis isolates was performed. DNA from all isolates of genomovars I and III and B. stabilis was amplified by G1-G2. Genomovar III isolates yielded a product with SPR3/G1 while B. stabilis amplified with SPR4-G1. Genomovar I isolates were amplified by either SPR3-G1 or SPR4-G1, but not both. B. multivorans yielded a product with SPR3-G1 but not G1-G2, and B. vietnamiensis isolates were negative in all PCRs. Thus using an algorithm with G1-G2, SPR3-G1, and SPR4-G1 primers in a PCR analysis, genomovar III isolates can be separated from B. stabilis and the identity of B. multivorans and B. vietnamiensis can be confirmed.     

Using the congestion quantifier seven-item test to assess change in patient symptoms and their impact.

Generally, nasal congestion is reported to be the most troublesome symptom of allergic rhinitis and has been shown to have negative effects on sleep, productivity, work, and school performance. A new patient-reported outcome (PRO) tool called the Congestion Quantifier Seven-Item Test (CQ7) was developed and shown to be a reliable and valid screening tool for nasal congestion. The purpose of this study was to assess the CQ7 as a tool for clinical use that can monitor changes in nasal congestion or determine if patients are showing meaningful improvement in symptoms. This study examined the responsiveness of the CQ7 to changes in nasal congestion and changes in relevant PRO to explore whether the CQ7 can serve as a monitoring tool and a valid screening tool for nasal congestion using latent growth curve models. Results showed that the CQ7 is sensitive to changes in patients' symptoms and their impact. Change in the CQ7 from baseline to day 15 was highly related to the change in symptom scores from baseline to day 15 (beta = -0.99); and regression coefficients for the relationships between the CQ7 and changes in the other PRO subscales also were very high (betas ranged from -0.79 to -0.95), lending evidence to support the use of the CQ7 as a monitoring tool. The large sizes of the coefficients suggest that the efficient, seven-item monitoring tool captures change in congestion very well. Analyses of responsiveness to change suggest that a three- to four-point improvement is meaningful to patients.     

Acute unilateral pulmonary nonventilation due to mucous plugs

Acute bronchial obstruction by mucous plugs may be manifested clinically by dyspnea, hypoxemia, and respiratory alkalosis mimicking pulmonary thromboembolism. In eight cases with complete interruption of ventilation to an entire lung, chest radiography failed to reveal the extent of the obstruction. Perfusion was substantially less affected than ventilation. Routine ventilation-perfusion scintigraphy with technetium-99m DTPA aerosol aids in the diagnosis of acute major bronchial obstruction in patients with suspected pulmonary thromboembolism.     

Cardiorespiratory responses to aerobic training by patients with postpoliomyelitis sequelae

We examined the cardiorespiratory responses of 16 patients with postpoliomyelitis sequelae to a 16-week aerobic exercise program. The patients exercised at 70% of maximal heart rate. Dependent variables were resting and maximal heart rates, systolic and diastolic blood pressures, maximum oxygen consumption, maximum carbon dioxide consumption, respiratory quotient, and maximum expired volume per unit time. The exercise group was superior to the control group in watts, exercise time, maximum expired volume per unit time, and maximum oxygen consumption. No untoward events or loss of leg strength occurred as a result of the exercise regimen. We conclude that the aerobic training program employed in this study is a safe, short-term procedure and that patients with postpolio sequelae respond to training in a manner similar to healthy adults.     

Alteration of cross-bridge kinetics by myosin light chain phosphorylation in rabbit skeletal muscle: implications for regulation of actin-myosin interaction.

Myosin light chain phosphorylation in permeable skeletal muscle fibers increases isometric force and the rate of force production at submaximal levels of calcium activation; myosin light chain phosphorylation may underlie the increased rate and extent of force production associated with isometric twitch potentiation in intact fibers. To understand the mechanism by which myosin light chain phosphorylation manifests these effects, we have measured isometric force, isometric stiffness, rate of isometric force redevelopment after isotonic shortening, and isometric ATPase activity in permeabilized rabbit psoas muscle fibers. These measurements were made in the presence and absence of myosin light chain phosphorylation over a range of calcium concentrations that caused various levels of activation. The results were analyzed with a two-state cross-bridge cycle model as suggested by Brenner [Brenner, B. (1988) Proc. Natl. Acad. Sci. USA 85, 3265-3269]. The results indicate that myosin light chain phosphorylation exerts its effect on force generation and the isometric rate of force redevelopment in striated muscle through a single mechanism, namely, by increasing the rate constant describing the transition from non-force-generating cross-bridges to force-generating states (fapp). gapp, the reverse rate constant, is unaffected by phosphorylation as are the number of cycling cross-bridges. Since both calcium and myosin light chain phosphorylation increase fapp, the possibility is considered that modulation of fapp may represent a general mechanism for regulating force in actin-myosin systems.