Unexpected frequency of idiopathic costochondral pain

A study of the records of patients seen in a two-year period in a private gynecologic practice and a one-year period in the emergency department of a general hospital was prompted by the incidence of chest wall pain diagnosed as costochondral pain. The study revealed 76 women in the former practice and 156 men and women in the latter with this condition. Physicians need to understand this symptom complex and be aware of the frequency of its occurrence in patients presenting with chest pain and fearing breast cancer or cardiac disease. Costly, intensive investigation can be avoided when careful, deep palpation of the costochondral junction discloses pain traversing the rib under the breast, leading to a diagnosis of idiopathic costochondral pain.     

Carcinogen exposure during short-term switching from regular to "light" cigarettes.

OBJECTIVES: "Light" cigarettes are extremely popular and are perceived by many smokers as less hazardous than higher-yield cigarettes. The objectives of this study were (a) to assess a battery of biomarkers of tobacco smoke exposure that includes tobacco smoke carcinogens, (b) to examine the behavioral nature of compensation, and (c) to examine the consistency of an individual's tobacco smoke exposure when smoking the same cigarette at different times. METHODS: The study was a 3-week crossover study in which smokers smoked their usual cigarettes during weeks 1 and 3, and a light cigarette, with a machine-determined nicotine yield of about 50% of the usual cigarette, during week 2. Blood and urine biomarkers of exposure and subjective questionnaires were collected weekly. RESULTS: Based on cotinine and carboxyhemoglobin levels, compensation averaged 78% and 83%, respectively. Urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol, a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-butanone, and a number of polycyclic aromatic hydrocarbon metabolites was similar in all conditions. Compensation was accomplished both by smoking cigarettes more intensively and by smoking more cigarettes per day. Exposures to various tobacco smoke constituents while smoking the usual brand of cigarette in weeks 1 and 3 were highly correlated. CONCLUSION: Our findings support the idea that smokers compensate to a high degree when switched from their usual brand to a light cigarette. Short-term switching resulted in no significant reduction in carcinogen exposure. Our assessment, based on measures of biochemical exposures, supports the idea that switching to light cigarettes is unlikely to reduce the health risks of cigarette smoking.     

Metabolism and disposition kinetics of nicotine

Nicotine is of importance as the addictive chemical in tobacco, pharmacotherapy for smoking cessation, a potential medication for several diseases, and a useful probe drug for phenotyping cytochrome P450 2A6 (CYP2A6). We review current knowledge about the metabolism and disposition kinetics of nicotine, some other naturally occurring tobacco alkaloids, and nicotine analogs that are under development as potential therapeutic agents. The focus is on studies in humans, but animal data are mentioned when relevant to the interpretation of human data. The pathways of nicotine metabolism are described in detail. Absorption, distribution, metabolism, and excretion of nicotine and related compounds are reviewed. Enzymes involved in nicotine metabolism including cytochrome P450 enzymes, aldehyde oxidase, flavin-containing monooxygenase 3, amine N-methyltransferase, and UDP-glucuronosyltransferases are represented, as well as factors affecting metabolism, such as genetic variations in metabolic enzymes, effects of diet, age, gender, pregnancy, liver and kidney diseases, and racial and ethnic differences. Also effects of smoking and various inhibitors and inducers, including oral contraceptives, on nicotine metabolism are discussed. Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme.     

Short-term metabolic and hemodynamic effects of ephedra and guarana combinations

OBJECTIVE: Serious adverse health events have been reported with the use of dietary supplements containing ephedra and guarana. We sought to determine whether repeated dosing and multi-ingredient formulations contribute to the adverse effects of these supplements. METHODS: In this study, 16 healthy adults (8 women) took 2 doses each of ephedra-guarana alone, Xenadrine RFA, a multicomponent dietary supplement containing 25 mg ephedra alkaloids and 200 mg caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover study. RESULTS: Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared with placebo, Xenadrine and ephedra-guarana significantly increased heart rate (maximum increase, 9.4 +/- 8.6 beats/min; P = .002), blood pressure (maximum increase in systolic and diastolic pressure, 11.5 +/- 10.7 mm Hg and 7.3 +/- 7.4 mm Hg, respectively; P = .015), postprandial glucose concentration (maximum change, 41.0 +/- 18.8 mg/dL; P < .0001), and insulin concentration (maximum change, 41.2 +/- 47.8 microIU/mL; P = .005). Serum potassium concentrations were significantly decreased by both treatments. Hemodynamic and metabolic changes were observed after both the first and second doses. However, plasma free fatty acid concentrations increased after the first dose only. Xenadrine RFA produced higher increases in glucose concentration than ephedra-guarana, but no other pharmacodynamic differences between the treatments were found. CONCLUSIONS: Consumption of 2 doses of ephedra and guarana supplements, per supplement label recommendations, results in persistent increases in heart rate and blood pressure and unfavorable actions on glucose and potassium homeostasis. Such effects could be detrimental in persons with hypertension, atherosclerosis, or glucose intolerance, conditions that are strongly associated with obesity.     

Inhomogeneity of ventilation leads to unpredictable errors in measured D(L)CO

We evaluated the effects of inhomogeneity of ventilation on single-breath (SB), rebreathing (RB) and open circuit (OC) D(L)CO using a mathematical model consisting of two alveolar compartments and a common dead space. Inhomogeneity in ventilation was studied by altering inspired volume, initial alveolar volume and compartment size independently. When distribution of inspired volume between alveolar compartments was inhomogeneous (9:1), D(L)CO was underestimated by 35% for SB, 25% for RB, and 16% for OC, and there was an underestimation in V(A) of 9%, 15% and 9%, respectively. With inhomogeneity in initial alveolar volume there was an overestimation in D(L)CO of 13%, 7% and 11% for SB, RB and OC techniques and an underestimation of V(A) of 7%, 12% and 9%. Finally inhomogeneity of compartment size led to an underestimation of D(L)CO of 18%, 35% and 36% with no change in measured V(A). These results suggest D(L)CO measurements are sensitive to inhomogeneity of ventilation, and importantly, all techniques were at times, significantly in error.     

Is cidofovir a useful adjunctive therapy for recurrent respiratory papillomatosis in children?

OBJECTIVE: To assess the usefulness of cidofovir in treating recurrent respiratory papillomatosis in children. Cidofovir is an acyclic nucleoside phosphonate that has been reported to be effective in the treatment of respiratory papillomatosis in several small series of patients. METHODS: A prospective study was conducted in 11 children (mean, 2.1 years; range, 0.5-3 years at diagnosis) with recurrent respiratory papillomatosis who at the start of the study were requiring debridement of papillomas at least every 6 weeks. After microlaryngoscopy with powered microdebridement of papillomas patients received intralesional injection of cidofovir (5mg/ml). The severity of papillomatosis was rated at each visit using a standardized papilloma severity scoring system. The success of therapy was measured by the trend in the patient's papilloma severity scores before and after cidofovir therapy and by whether the frequency of operative interventions decreased in the period after treatment began. RESULTS: Three patients had impressive improvements in severity scores and a decrease in the frequency of required operative interventions after cidofovir, two patients had a partial response, and for six patients cidofovir was considered ineffective. CONCLUSIONS: Intralesional cidofovir did not decrease the severity or frequency of operative intervention for recurrent respiratory papillomas in the majority of children in this study. The drug did improve papillomatosis in the minority of patients without causing notable morbidity. A large multi-institutional controlled study is needed to better assess the efficacy of this treatment.     

Fraction of free-base nicotine in fresh smoke particulate matter from the Eclipse "cigarette" by 1H NMR spectroscopy

Solution 1H NMR (proton-NMR) spectroscopy was used to measure the distribution of nicotine between its free-base and protonated forms at 20 degrees C in (a) water; (b) glycerin/water mixtures; and (c) puff-averaged "smoke" particulate matter (PM) produced by the Eclipse cigarette, a so-called "harm reduction" cigarette manufactured by R. J. Reynolds (RJR) Tobacco Co. Smoke PM from the Eclipse contains glycerin, water, nicotine, and numerous other components. Smoke PM from the Eclipse yielded a signal for the three N-methyl protons on nicotine at a chemical shift of delta (ppm) = 2.79 relative to a trimethylsilane standard. With alpha fb = fraction of the total liquid nicotine in free-base form, and alpha a = fraction in the acidic, monoprotonated NicH+ form, then alpha a + alpha fb approximately 1. (The diprotonated form of nicotine was assumed negligible.) When the three types of solutions were adjusted so that alpha a approximately 1, the N-methyl protons yielded delta a = 2.82 (Eclipse smoke PM); 2.79 (35% water/65% glycerin); and 2.74 (water). When the solutions were adjusted so that alpha fb approximately 1, the N-methyl protons yielded delta fb = 2.16 (Eclipse smoke PM); 2.13 (35% water/65% glycerin); and 2.10 (water). In all of the solutions, the rate of proton exchange between NicH+ and Nic was fast relative to the 1H-NMR chemical shift difference in hertz. Each solution containing both NicH+ and Nic thus yielded a single N-methyl peak at a delta given by delta = alpha a delta a + alpha fb delta fb so that delta varied linearly between delta a and delta fb. Since alpha fb = (delta a-delta)/(delta a-delta fb), then delta = 2.79 for the unadjusted Eclipse smoke PM indicates alpha fb approximately 0.04. The effective pH of the Eclipse smoke PM at 20 degrees C may then be calculated as pHeff = 8.06 + log[alpha fb/(1-alpha fb)] = 6.69, where 8.06 is the pKa of NicH+ in water at 20 degrees C. The measurements obtained for the puff-averaged Eclipse smoke PM pertain to the chemistry of the smoke PM as it might be initially inhaled at 20 degrees C. Upon inhalation, the volatilization of nicotine and other acid/base active compounds (as well as a warming toward a body temperature of 37 degrees C) will alter the pHeff value of the smoke PM during the time that it resides and ages in the respiratory tract.     

A novel model of pneumonia from intraperitoneal injection of bacteria

BACKGROUND: Pneumonia remains a major clinical problem in the surgical patient. Experimental modeling by intratracheal injection of bacteria is not consistently reproducible. In an attempt to produce peritonitis by Klebsiella, we found evidence of pneumonia on autopsy and further developed this approach as a new experimental model. METHODS: Male Swiss Webster mice were given intraperitoneal (IP) injections of Klebsiella pneumoniae serotype 2 in different doses and this was compared with similar doses given intravenously (IV). A dose dependent survival curve was generated. Subsequently, 10(3) colony forming units (CFU) of bacteria were used in further experiments. Blood, peritoneal fluid and lung tissue were collected at time points up to 72 hours after injection and were cultured for levels of bacteria. Lung weights and myeloperoxidase levels were also measured. RESULTS: Intraperitoneal administration of Klebsiella was uniformly lethal with as few as 10(2) bacteria. Lung weight increased after IP Klebsiella, and all animals became bacteremic within 24 hours correlating with high bacterial levels in the lung. Conversely, most animals (72%) survived IV injection of bacteria, and were able to clear bacteria from the blood and lung. CONCLUSIONS: We found that this model produced no clinically apparent peritonitis after 48 hours, but uniformly resulted in histopathologic changes of pneumonia by 24 hours. Survival time was related to initial dose of Klebsiella and there was a linear correlation between bacterial levels in the blood and lung. This model is reproducible, simple to perform, and the severity is easy to manipulate.     

Success and complications of four-duct ligation for sialorrhea

OBJECTIVE: Sialorrhea can have a significant negative effect on quality of life, impeding social interactions and severely limiting employment opportunities. Many surgical options to control sialorrhea have been reported. One of the newest procedures is combined ligation of the submandibular and parotid ducts, reported only once in the literature in one series of five patients to date. We have compared results in our first 21 patients undergoing this procedure with results reported in the literature for other procedures to treat sialorrhea. MATERIALS AND METHODS: We retrospectively reviewed medical records of all 21 children we treated with four-duct ligation, a relatively simple intraoral procedure to control sialorrhea, between August 1999 and September 2000 and contacted primary caregivers by telephone to answer a questionnaire regarding objective and subjective results of surgery. Surgery was considered successful when caregivers rated patients as 'much better' or 'better' after surgery. RESULTS: Follow-up was completed in all 21 of the patients 1-14 months after surgery. The success rate of four-duct ligation ('much better' or 'better' after surgery) was 81%, and no patient's sialorrhea problem was worse after surgery. Major complications occurred in two (10%) of the patients (one ranula and one case of sialoadenitis), which were both successfully treated surgically. Minor complications occurred in four (19%) of the patients, tongue swelling that prolonged hospitalization, a ranula that resolved, and prolonged submandibular gland swelling that resolved (two cases). More than half of patients were discharged the day of or the day after surgery. CONCLUSIONS: Four-duct ligation should be considered when surgery is indicated to treat sialorrhea.