ABSTRACT
Salmonella enteritidis (SE) is a major foodborne pathogen that causes human infections largely by consumption of contaminated eggs. The external surface of eggs becomes contaminated with SE from multiple sources, highlighting the need for effective egg surface disinfection methods. This study investigated the efficacy of three GRAS-status, phytochemicals, namely carvacrol (CR), eugenol (EG), and ß-resorcylic acid (BR) applied as pectin or gum arabic based coating for reducing SE on shell eggs. White-shelled eggs, spot inoculated with a 5-strain mixture of nalidixic acid (NA) resistant SE (8.0 log CFU/mL) were coated with pectin or gum arabic solution containing each phytochemical (0.0, 0.25, 0.5, or 0.75%), and stored at 4°C for 7 days. SE on eggs was enumerated on days 0, 1, 3, and 7 of storage. Approximately 4.0 log CFU/egg of SE was recovered from inoculated and pectin or gum arabic coated eggs on day 0. All coating treatments containing CR and EG, and BR at 0.75% reduced SE to undetectable levels on day 3 (P < 0.05). Results suggest that the aforementioned phytochemicals could effectively be used as a coating to reduce SE on shell eggs, but detailed studies on the sensory and quality attributes of coated eggs need to be conducted before recommending their use.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chickens , Egg Shell/microbiology , Microbial Viability , Poultry Diseases/prevention & control , Salmonella Infections, Animal/prevention & control , Salmonella enteritidis/drug effects , Animals , Cymenes , Eugenol/pharmacology , Gum Arabic/chemistry , Hydroxybenzoates/pharmacology , Monoterpenes/pharmacology , Pectins/chemistry , Phytochemicals/pharmacology , Poultry Diseases/microbiology , Salmonella Infections, Animal/microbiologyABSTRACT
PURPOSE: Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells (WBC). However, effects on the level of spontaneous DNA strand breaks, a well established marker of health risk, have not been specifically reported yet. We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA strand breaks. METHODS: Healthy men (n = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks. The study coffee was a blend providing high amounts of both caffeoylquinic acids (10.18 ± 0.33 mg/g) and the roast product N-methylpyridinium (1.10 ± 0.05 mg/g). Before and after the coffee/water consumption phase, spontaneous strand breaks were determined by comet assay. RESULTS: At baseline, both groups exhibited a similar level of spontaneous DNA strand breaks. In the intervention phase, spontaneous DNA strand breaks slightly increased in the control (water only) group whereas they significantly decreased in the coffee group, leading to a 27% difference within both arms (p = 0.0002). Food frequency questionnaires indicated no differences in the overall diet between groups, and mean body weight during the intervention phases remained stable. The consumption of the study coffee substantially lowered the level of spontaneous DNA strand breaks in WBC. CONCLUSION: We conclude that regular coffee consumption contributes to DNA integrity.
Subject(s)
Antioxidants/administration & dosage , Coffee , DNA Breaks , Food Handling , Leukocytes/metabolism , Adult , Alkaloids/administration & dosage , Alkaloids/analysis , Alkaloids/urine , Antioxidants/analysis , Biomarkers/blood , Caffeine/administration & dosage , Caffeine/analysis , Coffea/chemistry , Coffee/chemistry , Cohort Studies , Comet Assay , Germany , Hot Temperature , Humans , Male , Patient Compliance , Pyridinium Compounds/administration & dosage , Pyridinium Compounds/analysis , Pyridinium Compounds/urine , Quinic Acid/administration & dosage , Quinic Acid/analogs & derivatives , Quinic Acid/analysis , Seeds/chemistryABSTRACT
Coffee and caffeine are known to affect the limbic system, but data on the influence of coffee and coffee constituents on neurotransmitter release is limited. We investigated dopamine release and Ca(2+)-mobilization in pheochromocytoma cells (PC-12 cells) after stimulation with two lyophilized coffee beverages prepared from either Coffea arabica (AR) or Coffea canephora var. robusta (RB) beans and constituents thereof. Both coffee lyophilizates showed effects in dilutions between 1:100 and 1:10,000. To identify the active coffee compound, coffee constituents were tested in beverage and plasma representative concentrations. Caffeine, trigonelline, N-methylpyridinium, chlorogenic acid, catechol, pyrogallol and 5-hydroxytryptamides increased calcium signaling and dopamine release, although with different efficacies. While N-methylpyridinium stimulated the Ca(2+)-mobilization most potently (EC(200): 0.14±0.29µM), treatment of the cells with pyrogallol (EC(200): 48±14nM) or 5-hydroxytryptamides (EC(200): 10±3nM) lead to the most pronounced effect on dopamine release. In contrast, no effect was seen for the reconstituted biomimetic mixture. We therefore conclude that each of the coffee constituents tested stimulated the dopamine release in PC-12 cells. Since no effect was found for their biomimetic mixture, we hypothesize other coffee constituents being responsible for the dopamine release demonstrated for AR and RB coffee brews.
Subject(s)
Adrenal Gland Neoplasms/metabolism , Coffee/chemistry , Dopamine/metabolism , Pheochromocytoma/metabolism , Animals , Calcium/metabolism , Molecular Structure , PC12 Cells , Rats , Seeds/chemistryABSTRACT
BACKGROUND: Ragweed (Ambrosia artemisiifolia) and mugwort (Artemisia vulgaris) pollen is the main cause of allergic reactions in late summer and autumn. The differential diagnosis between ragweed and mugwort pollen allergy is a frequent problem encountered by allergologists in areas where both plants are present due to shared antigenic structures and overlapping flowering seasons. OBJECTIVE: To evaluate the sensitization pattern of weed allergic patients towards a large panel of purified allergens in the microarray format and by enzyme-linked immunosorbent assay (ELISA). METHODS: Eight ragweed and six mugwort pollen allergens were purified from natural source or expressed as recombinant proteins in Escherichia coli. Allergens were spotted on protein microarray slides or coated onto ELISA plates. Sera from 19 ragweed and/or mugwort allergic individuals were used to determine the reactivity towards single molecules in both assays. RESULTS: All ragweed allergic individuals were sensitized to Amb a 1, among them 30% were monosensitized to the major ragweed allergen. Art v 1 and Art v 3 were recognized by 89% of mugwort pollen-allergic patients. Extensive cross-reactivity was observed for both patient groups mainly involving the pan-allergens profilin and nonspecific lipid transfer proteins. Comparable IgE profiles were obtained with both allergen microarray and ELISA methods. CONCLUSIONS: Molecule-based diagnosis provides essential information for the differential diagnosis between ragweed and mugwort pollen allergy and for the selection of the appropriate allergen source for specific immunotherapy.
Subject(s)
Allergens/immunology , Ambrosia/immunology , Artemisia/immunology , Immunoglobulin E/blood , Pollen/immunology , Protein Array Analysis , Rhinitis, Allergic, Seasonal/diagnosis , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Humans , Plant Extracts/immunology , Recombinant Proteins/immunology , Rhinitis, Allergic, Seasonal/immunologyABSTRACT
Consumption of coffee beverages has been reported to cause gastric irritation in some consumers as a result of increased gastric acid secretion. In the complex mechanisms of gastric acid secretion, the activity and expression of the H+,K+-ATPase is regulated by transmitters, such as histamine, acetylcholine, gastrin, somatostatin, and their corresponding receptors. Here, we report the effect of three coffee constituents, chlorogenic acid, caffeine, and N-methyl pyridinium ions, on the expression of the histamine receptor H2, the acetylcholine receptor M3, the gastrin receptor, the somatostatin receptor, and the H+,K+-ATPase. Human gastric cancer cells were exposed to chlorogenic acid, caffeine, or N-methyl pyridinium in their coffee brew-representative concentrations as well as to physiological stimulators of gastric acid secretion. Gene expression levels of receptor proteins and those of the H+,K+-ATPase were measured at different time points by real-time PCR. Expression of prosecretory receptors significantly increased between one and one-half to twofold after treatment with chlorogenic acid or caffeine compared to control cells at the same time point. Chlorogenic acid and caffeine also increased the H+,K+-ATPase gene expression twofold higher compared to control cells. In contrast, N-methyl pyridinium downregulated the expression of the prosecretory gastrin receptor significantly, by -27%. In conclusion, chlorogenic acid, caffeine, and N-methyl pyridinium impair the expression of gastric acid secretion-related proteins in a time-dependent manner. Future work will be aimed at the elucidation of the cooperative interplay of individual components using recombinates of single coffee constituents.
Subject(s)
Coffee , Gastric Juice/metabolism , Beverages , Cells, Cultured , Chlorogenic Acid/pharmacology , Cooking , Gastric Juice/drug effects , Gastric Juice/enzymology , Gastrins/pharmacology , H(+)-K(+)-Exchanging ATPase/metabolism , Humans , Kinetics , Somatostatin/pharmacologyABSTRACT
BACKGROUND: The incidence of Zenker's diverticulum is low (2/100,000). Standard surgical treatment is cricopharyngeal myotomy with diverticulectomy. Various minimally invasive surgical approaches pursued recently have treated Zenker's diverticulum adequately. The functional minimally invasive therapy is performed alternatively using an Endo-Gia stapler inserted transorally to perform an esophageal diverticulostomia, or using thermal coagulation applied by a carbon dioxide (CO2) or argon plasma laser. The key to a successful procedure is adequate exposure of the diverticulum by insertion of a pharynx spreader before the surgery. METHODS: Since 1996, 31 patients who underwent minimally invasive diverticulostomies performed in our clinic have been included prospectively in the current study. All the patients were examined endoscopically before and after surgery. Furthermore, the intraesophageal and intragastric pressure was examined by transesophageal manometry, and the pH in the esophagus and stomach was determined by pH-metry. A barium swallow was performed to exclude leakage at the stapler suture line as proof of sufficient anastomoses. Manometry showed that the upper esophageal sphincter functioned normally before and after surgery. The results were compared with those of patients undergoing conventional procedures. RESULTS: The median follow-up period after resection of the diverticulum was 46 months. Both the Gastrointestinal Quality-of-Life Index (GQLI) (p < 0.001) and the modified dysphagia score (GHDS) increased significantly, indicating that the operations were successful. The minimally invasive procedure is faster than cricopharyngeal myotomy and significantly safer. It is better tolerated by patients, and they are discharged earlier. CONCLUSION: Transoral esophagodiverticulosomy has become the standard procedure for Zenker's diverticulum in the authors' department. The endoscopic minimally invasive approach proved to be safer than standard surgical procedures. It offers a significantly shorter operation time and postoperative hospital stay (p < 0.001).
Subject(s)
Esophagoscopy/methods , Quality of Life , Surgical Staplers , Zenker Diverticulum/diagnosis , Zenker Diverticulum/surgery , Adult , Aged , Aged, 80 and over , Equipment Design , Equipment Safety , Esophagoscopy/adverse effects , Female , Follow-Up Studies , Germany , Humans , Intraoperative Complications/physiopathology , Male , Manometry , Middle Aged , Minimally Invasive Surgical Procedures/adverse effects , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/physiopathology , Probability , Prospective Studies , Retrospective Studies , Risk Assessment , Severity of Illness Index , Statistics, Nonparametric , Treatment OutcomeABSTRACT
Rheumatoid arthritis (RA) is a debilitating disease and is associated with increased risk of cardiovascular disease and osteoporosis. Poor nutrient status in RA patients has been reported and some drug therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed to alleviate RA symptoms, may increase the requirement for some nutrients and reduce their absorption. This paper reviews the scientific evidence for the role of diet and nutrient supplementation in the management of RA, by alleviating symptoms, decreasing progression of the disease or by reducing the reliance on, or combating the side-effects of, NSAIDs. Supplementation with long-chain n-3 polyunsaturated fatty acids (PUFA) consistently demonstrates an improvement in symptoms and a reduction in NSAID usage. Evidence relating to other fatty acids, antioxidants, zinc, iron, folate, other B vitamins, calcium, vitamin D and fluoride are also considered. The present evidence suggests that RA patients should consume a balanced diet rich in long-chain n-3 PUFA and antioxidants. More randomized long-term studies are needed to provide evidence for the benefits of specific nutritional supplementation and to determine optimum intake, particularly for n-3 PUFA and antioxidants.
Subject(s)
Arthritis, Rheumatoid/diet therapy , Nutritional Physiological Phenomena , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Arthritis, Rheumatoid/drug therapy , Calcium, Dietary/administration & dosage , Dietary Supplements , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Folic Acid/administration & dosage , Humans , Nutritional Status , Vitamin B Complex/administration & dosage , Vitamin D/administration & dosageABSTRACT
The cytokines IL-4 and IL-13 inhibit the production of NO from activated macrophages through an unresolved molecular mechanism. We show here that IL-4 and IL-13 regulate NO production through depletion of arginine, the substrate of inducible NO synthase (iNOS). Inhibition of NO production from murine macrophages stimulated with LPS and IFN-gamma by IL-4 or IL-13 was dependent on Stat6, cell density in the cultures, and pretreatment for at least 6 h. IL-4/IL-13 did not interfere with the expression or activity of iNOS but up-regulated arginase I (the liver isoform of arginase) in a Stat6-dependent manner. Addition of exogenous arginine completely restored NO production in IL-4-treated macrophages. Furthermore, impaired killing of the intracellular pathogen Toxoplasma gondii in IL-4-treated macrophages was overcome by supplementing L-arginine. The simple system of regulated substrate competition between arginase and iNOS has implications for understanding the physiological regulation of NO production.
Subject(s)
Nitric Oxide/biosynthesis , Trans-Activators/physiology , Animals , Arginase/biosynthesis , Arginine/deficiency , Cells, Cultured , Down-Regulation/immunology , Interleukin-13/physiology , Interleukin-4/physiology , Macrophage Activation , Macrophages, Peritoneal/enzymology , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/parasitology , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , STAT6 Transcription Factor , Substrate Specificity/immunology , Toxoplasmosis, Animal/enzymology , Toxoplasmosis, Animal/immunology , Toxoplasmosis, Animal/metabolism , Trans-Activators/deficiency , Trans-Activators/geneticsABSTRACT
Although myocardial ischemia impairs left ventricular (LV) relaxation before contractile function, regional LV diastolic dysfunction is difficult to evaluate by conventional echocardiography. Because beta-adrenergic stimulation enhances myocardial relaxation, we sought to characterize segmental LV diastolic function (by color kinesis) during dobutamine stress echocardiography and compare it with independently assessed segmental systolic function. We studied 22 patients with suspected coronary artery disease with color kinesis by acquiring digital images with endocardial motion display throughout diastole. Quantification of LV segmental diastolic peak filling rate (SPFR, normalized to segmental end-diastolic area/s) was obtained at rest, low-dose, and peak dobutamine infusion in myocardial segments visualized from the short-axis and/or apical 4-chamber views. In patients with resting normal LV systolic function and a dobutamine-induced hypercontractile response (group I, n = 13 patients; 102 segments), progressive increases in SPFR (p <0.001) were seen in all segments. However, in LV segments with resting systolic wall motion abnormalities (group II, n = 9 patients; 74 segments) SPFR measured at rest was significantly lower than that in group I (p <0.005) and did not increase significantly in response to dobutamine. In both groups of patients, LV myocardial segments (n = 528; rest and after dobutamine)-systolic and quantitative diastolic function-were concordant in 84% and 77% as viewed from short-axis and apical views, respectively. Thus, segmental LV diastolic function can be measured with color kinesis at rest and after inotropic stimulation, allowing comparison with segmental systolic function during pharmacologic stress testing.
Subject(s)
Cardiotonic Agents/pharmacology , Dobutamine/pharmacology , Echocardiography, Doppler, Color , Ventricular Function, Left/drug effects , Aged , Blood Flow Velocity , Coronary Disease/diagnostic imaging , Coronary Disease/physiopathology , Exercise Test , Female , Humans , Male , Middle Aged , Myocardial Contraction , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Function, Left/physiologyABSTRACT
Several lines of evidence suggest that obese individuals have a higher set point for body weight regulation relative to lean subjects. Since obese rodents and humans have high serum levels of leptin, it has been hypothesized that this may be the result of an insensitivity to this weight reducing hormone. In this experiment we assessed whether feeding of a high-fat diet to rats affects leptin receptor (OB-R) transcript levels or induces up-regulation of the suppressors of leptin/cytokine induced signaling, SOCS-3 and PIAS-3. We found that despite a significant weight gain associated with markedly increased circulating leptin levels neither OB-R gene expression nor SOCS-3 or PIAS-3 mRNA levels were significantly altered in the high-fat fed rats. This was in contrast to control experiments where administration of exogenous leptin induced a several-fold increase in SOCS-3. It is concluded that high-caloric food intake per se is not sufficient to provoke suppression of leptin signaling via these factors in animals without genetic predisposition to obesity.
Subject(s)
Carrier Proteins/metabolism , Dietary Fats/administration & dosage , Proteins/metabolism , Receptors, Cell Surface , Repressor Proteins , Signal Transduction , Transcription Factors , Adipose Tissue, Brown/metabolism , Animals , Body Weight , Carrier Proteins/genetics , DNA Primers/chemistry , Epididymis/metabolism , Epididymis/pathology , Hypothalamus/metabolism , Leptin/blood , Leptin/pharmacology , Male , Proteins/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptors, Leptin , Reverse Transcriptase Polymerase Chain Reaction , Suppressor of Cytokine Signaling 3 Protein , Suppressor of Cytokine Signaling ProteinsABSTRACT
Besides an isomer of the cardenolide ouabain, a material with a similar HPLC retention time as ouabain but cross-reactivating with antibodies against the bufadienolide proscillaridin A and inhibiting the sodium pump is known to circulate in human blood plasma (B. SICH et al., Hypertension 27, 1073-1078 (1996).). The concentrations of both substances are known to correlate with the blood pressure. It was the intention of this work to localize tissues that contain the highest concentrations of the proscillaridin A immunoreactive material, to correlate its concentration with that of ouabain and to get information whether the concentration of this material simply reflects the number of sodium pumps of the tissue extracted. Specific antibodies for each cardiotonic steroid were used to test the tissue concentration. This report shows that in bovine tissues the distribution pattern of proscillaridin A and ouabain immunoreactivities are similar and that hypothalamus and adrenals show the highest concentrations. The cross-reactive material did not reflect the number of sodium pumps per g of wet weight tissue as measured by [3H]ouabain binding. Therefore, it is unlikely that the tissue concentrations in both immunoreactivities reflects the tissue capacity of sodium pumps labeled with cardiotonic steroids via the blood plasma. The study rather favors the concept that two different types of inhibitors of the sodium pump exist within both tissues.
Subject(s)
Adrenal Glands/metabolism , Cardiotonic Agents/metabolism , Hypothalamus/metabolism , Ouabain/metabolism , Proscillaridin/metabolism , Animals , Cardiotonic Agents/immunology , Cattle , Chromatography, High Pressure Liquid , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Humans , Ouabain/immunology , Proscillaridin/immunology , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
This article focuses on the application of a new business computing model--Objects. Although Object Technology is not new, its widespread use in healthcare information management executives struggle with the integration demands of the new enterprise, Object Technology will unleash the true power of desktop computing and lessen the many quandaries faced with the integration and aggregation of strategic enterprise data. As we move forward, the new healthcare business model will attempt to create the "virtual enterprise." This new enterprise, will be lean and nimble and allow the Integrated Delivery System (IDS) to deliver care to a broader population with fewer requirements for expensive and scarce resources. To do this, the IDS must possess the technology to share key data, with partners and providers, that will allow faster and more accurate decision making. This article presents the "natural fit" of Object Technology and its ability to solve the complex computing issues of the new healthcare enterprise.
Subject(s)
Decision Support Systems, Management , Delivery of Health Care, Integrated/organization & administration , Computer Simulation , Disease/classification , Humans , Microcomputers , Models, Organizational , Systems Integration , United States , Vocabulary, ControlledABSTRACT
Bacteriologic response to cefuroxime axetil and cefaclor administered for 10 days was evaluated in acute otitis media (AOM) in patients aged 6-36 months. Middle ear fluid culture was obtained by tympanocentesis before treatment, on day 4 or 5 after initiation of treatment, and if clinical relapse occurred before day 17. Bacteriologic failure was observed in 32% of patients receiving cefaclor versus 15% of patients receiving cefuroxime axetil (P = .009). Failure rates increased with increasing MIC: For Streptococcus pneumoniae, 0.5 microg/mL (established as cutoff value for cefuroxime by the National Committee for Clinical Laboratory Standards [NCCLS]) discriminated between success and failure. For Haemophilus influenzae, high failure rates were observed for cefaclor, even with low MICs (< or = 1.0 microg/mL), and with both drugs they tended to increase with increasing MIC, even for values below the cutoff suggested by the NCCLS (8.0 and 4.0 microg/mL for cefaclor and cefuroxime, respectively). Thus, for AOM caused by H. influenzae, lower susceptibility cutoff levels for MICs should be established.
Subject(s)
Cephalosporins/therapeutic use , Haemophilus influenzae/drug effects , Otitis Media/drug therapy , Streptococcus pneumoniae/drug effects , Acute Disease , Administration, Oral , Cefaclor/therapeutic use , Cefuroxime/analogs & derivatives , Cefuroxime/therapeutic use , Cephalosporins/pharmacology , Child, Preschool , Female , Humans , Infant , Male , Microbial Sensitivity Tests , Otitis Media/microbiologyABSTRACT
BACKGROUND: Penicillin resistance of Streptococcus pneumoniae, one of the most common causes of acute otitis media, has recently increased and is now highly prevalent in many regions. However, its contribution to clinical failure still must be proved. Because the role of antibiotics in acute otitis media is to eradicate the pathogens present in the middle ear fluid, we conducted a randomized controlled study to determine bacterial eradication of pathogens in acute otitis media by two commonly used oral cephalosporins, cefuroxime axetil (30 mg/kg/day) and cefaclor (40 mg/kg/day). METHODS: Patients 6 to 36 months old with pneumococcal otitis media seen in the Pediatrics Emergency Room were studied. An initial middle ear fluid culture was obtained at enrollment, and a second culture was obtained on Day 4 or 5 during treatment. Follow-up was done also on Days 10, 17 and 42 after initiation of treatment. In cases of clinical relapse a third culture was obtained. RESULTS: In total 78 patients were enrolled, 41 in the cefuroxime axetil group and 37 in the cefaclor group. Of the 78 S. pneumoniae isolates 31 (40%) were intermediately penicillin-resistant (MIC 0.125 to 1.0 microgram/ml). Of the 47 patients with penicillin-susceptible organisms 3 (6%) had bacteriologic failure vs. 4 of 19 (21%) and 7 of 11 (64%) of those with MIC of 0.125 to 0.25 microgram/ml and 0.38 to 1.0 microgram/ml, respectively (P < 0.001). For intermediately resistant pneumococci, in 7 of 12 (58%) of those receiving cefaclor the isolate was not eradicated vs. only 4 of 19 (21%) of those receiving cefuroxime axetil (P = 0.084). MIC to the administered cephalosporin of > 0.5 microgram/ml was associated with bacteriologic failure. Clinical failure was observed in 9 of 14 (64%) patients with bacteriologic failure vs. 10 of 52 (19%) patients with bacteriologic eradication (P = 0.003). CONCLUSION: Intermediately penicillin-resistant S. pneumoniae is associated with an impaired bacteriologic and clinical response of acute otitis media to cefaclor and cefuroxime axetil. This effect was more pronounced with cefaclor than with cefuroxime axetil.
Subject(s)
Cefaclor/therapeutic use , Cefuroxime/analogs & derivatives , Cephalosporins/therapeutic use , Otitis Media/drug therapy , Pneumococcal Infections/drug therapy , Acute Disease , Administration, Oral , Cefaclor/administration & dosage , Cefuroxime/administration & dosage , Cefuroxime/therapeutic use , Cephalosporins/administration & dosage , Child, Preschool , Drug Resistance, Microbial , Humans , Infant , Microbial Sensitivity Tests , Otitis Media/microbiology , Penicillin Resistance , Prospective Studies , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purificationABSTRACT
BACKGROUND: A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MVO2). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MVO2. METHODS AND RESULTS: Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MVO2, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or ACL. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MVO2 per beat was reduced with these agents. Stress-time index, a measure of MVO2 per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol. CONCLUSIONS: The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MVO2 in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MVO2 with each drug may provide a more physiological approach to the treatment of systemic hypertension in indivi
Subject(s)
Antihypertensive Agents/therapeutic use , Black People , Hemodynamics/drug effects , Hypertension/drug therapy , Hypertension/ethnology , Ventricular Function, Left/drug effects , Administration, Oral , Analysis of Variance , Atenolol/therapeutic use , Cross-Over Studies , Double-Blind Method , Echocardiography , Female , Humans , Hypertension/physiopathology , Male , Middle Aged , Nifedipine/therapeutic use , Ramipril/therapeutic use , Time Factors , Ultrasonography, DopplerABSTRACT
Mice infected with Brucella melitensis were treated with azithromycin or roxithromycin at a dose of 50 mg/kg/day i.p. alone and in combination with streptomycin 75 mg/kg/day for 14 days. Streptomycin at this dose was previously documented to be ineffective against murine brucellosis. Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls. Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p. alone or in combination with streptomycin 75 mg/kg/day. Our findings demonstrate that azithromycin cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.
Subject(s)
Azithromycin/therapeutic use , Brucella melitensis , Brucellosis/drug therapy , Roxithromycin/therapeutic use , Animals , Azithromycin/pharmacokinetics , Brucella melitensis/growth & development , Brucellosis/microbiology , Colony Count, Microbial , Mice , Microbial Sensitivity Tests , Roxithromycin/pharmacokineticsABSTRACT
The in vivo efficacy of streptomycin (STR), doxycycline (DOX), rifampin (RIF), ciprofloxacin (CIP), and their combinations was evaluated for a Brucella melitensis experimental infection in a mouse model. Animals were infected with 2 x 10(4) to 4 x 10(4) CFU of B. melitensis intraperitoneally on day 0 and were randomized to receive, starting on day 7, STR alone at 75, 150, or 300 mg/kg of body weight per day intraperitoneally or DOX at 6 mg/kg/day orally, RIF at 3 mg/kg/day orally, or CIP at 200 mg/kg/day orally, each of the last three drugs alone or in combination with STR at 75, 150, or 300 mg/kg/day, for 14 days. Therapy failure (defined as nonsterile spleens) was observed in all animals treated with STR at all doses and with CIP given as monotherapy. Mean log CFU isolated from the spleens remaining infected following monotherapy with STR or CIP were not different from those in control mice. RIF at a low dose did not have an effect on cure rates; however, a reduction in CFU relative to the CFU in untreated animals was obtained. DOX at low levels achieved a 35% cure rate and a reduction in CFU in animals not cured. All animals treated with DOX or RIF combined with any STR dose were cured, but none of the animals receiving the STR-CIP combinations was cured, and the splenic CFU remained similar to those in the controls. These results demonstrate that the combinations DOX-STR and RIF-STR are synergistic against B. melitensis, while the combination STR-CIP is indifferent and ineffective in the management of acute murine brucellosis. The results also appear to support the clinical superiority of combination drug therapy over monotherapy.
Subject(s)
Brucellosis/drug therapy , Drug Therapy, Combination/therapeutic use , Streptomycin/therapeutic use , Animals , Body Weight/drug effects , Brucella/drug effects , Brucellosis/microbiology , Ciprofloxacin/pharmacokinetics , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Colony Count, Microbial , Doxycycline/pharmacokinetics , Doxycycline/pharmacology , Doxycycline/therapeutic use , Drug Synergism , Drug Therapy, Combination/pharmacokinetics , Drug Therapy, Combination/pharmacology , Male , Mice , Mice, Inbred ICR , Microbial Sensitivity Tests , Organ Size/drug effects , Rifampin/pharmacokinetics , Rifampin/pharmacology , Rifampin/therapeutic use , Spleen/drug effects , Spleen/microbiology , Streptomycin/pharmacokinetics , Streptomycin/pharmacologyABSTRACT
The current medical management of children with chronic suppurative otitis media without cholesteatoma unresponsive to local treatment and oral antibiotics is intravenous antibiotic therapy in the hospital setting. We studied the efficacy and toxicity of oral ciprofloxacin in chronic suppurative otitis media. Twenty-one children received oral ciprofloxacin, 30 mg/kg/day. Ear discharge was positive for bacteria resistant to other oral medications and susceptible to the quinolones. The mean duration of treatment was 16.7 days. In 18 children suppuration ceased and 3 failed their first course. During a mean follow-up of 15.4 months, 6 children remained free of ear, nose and throat problems. Otorrhea recurred in 12 children. Ear cultures were positive for organisms susceptible to amoxicillin in 5 of them. In 7 cases Pseudomonas aeruginosa was again isolated from otorrhea. Repeated antibiotic therapy was advocated only in 3 (2 responded to ciprofloxacin; 1 failed ciprofloxacin and was cured by ceftazidime). Adverse clinical effects were not observed. Transient neutropenia was observed in 1 child. There was no change in the height percentile. The results of this study show that children with chronic suppurative otitis media without cholesteatoma can be effectively treated with oral ciprofloxacin. This novel approach may prevent hospitalization.
Subject(s)
Ciprofloxacin/therapeutic use , Otitis Media, Suppurative/drug therapy , Administration, Oral , Adolescent , Child , Child, Preschool , Cholesteatoma , Chronic Disease , Ciprofloxacin/administration & dosage , Female , Humans , Infant , MaleABSTRACT
Mice infected with Brucella melitensis were treated with streptomycin, co-trimoxazole, ciprofloxacin, doxycycline, and rifampin intraperitoneally and with ciprofloxacin, ofloxacin, pefloxacin, doxycycline, and rifampin orally for 14 to 21 days. Doxycycline- and rifampin-treated animals (either route) demonstrated a cure rate significantly better than that of controls. Longer therapy periods were associated with a significantly better outcome. Therapy failure was observed in all mice treated with ciprofloxacin, ofloxacin, and pefloxacin administered orally as well as in mice treated intraperitoneally with ciprofloxacin. Our findings demonstrate that treatment of experimental brucellosis in mice with doxycycline and rifampin yields therapeutic results that are superior to those yielded by treatment with quinolones.