Evaluation of species-specific score cutoff values of routinely isolated clinically relevant bacteria using a direct smear preparation for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based bacterial identification.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was introduced a few years ago as a new method for bacterial identification. A variety of studies have been published concerning MALDI-TOF MS-based identification, most of them using culture collections for the validation of the respective databases in a retrospective manner in favor of a parallel investigation. The score cutoff value is of special importance for reliable species identification in the Biotyper database. The score cutoff values suggested by the manufacturer have been validated using a previously published formic acid extraction protocol. In most of the previously published studies investigating the Biotyper database, only little information was given concerning species-specific score values. In addition, the mass spectrometer instruments, the number of replicates, the number of spectra used to calculate a sum-spectrum by the supplied software, and the score cutoff values which have been applied varied within these studies. In this study, we compared a straightforward direct smear preparation and measurement without replicate testing to defined biochemical identifications in a parallel manner. In addition, we described new species-specific score cutoff values for the identification of certain bacteria.

Developing a digitally innovative ethics and professionalism curriculum for neonatal-perinatal medicine fellows: a 3-year multicenter pilot study.

OBJECTIVES: The purpose of this study was to develop and regionally pilot a digitally innovative curriculum in ethics and professionalism in neonatology and study the effects on trainee knowledge and confidence. STUDY DESIGN: We developed 13 modules in ethics for neonatology fellows and piloted them at three academic institutions utilizing a flipped-classroom approach. Baseline surveys in ethics knowledge and confidence in approaching ethical dilemmas were compared with repeat surveys after curriculum completion. Pre- and post-tests were also administered for all 13 modules. RESULTS: Forty-four of 49 eligible fellows participated (90% response rate). Pre/post comparisons demonstrated significant improvements in overall knowledge and in 8/13 modules, as well as improvement in overall confidence and individually when navigating 16/22 ethical dilemmas. CONCLUSIONS: After completing this curriculum, participants' knowledge scores and reported confidence in approaching ethical challenges significantly improved. Future steps include assessing the effects of this innovative curriculum via an ongoing international pilot.

Effects of celecoxib and naproxen on renal function in the elderly.

OBJECTIVE: To compare the effects of celecoxib, a cyclooxygenase 2-specific inhibitor, with the nonspecific cyclooxygenase 1 and 2 inhibitor naproxen on renal function in 29 healthy elderly subjects in a single-blind, randomized, crossover study. METHODS: Subjects received either celecoxib, 200 mg twice daily, for 5 days followed by celecoxib, 400 mg twice daily, for the next 5 days, or they received naproxen, 500 mg twice daily, for 10 days. After a 7-day washout, subjects were crossed over to receive the other regimen. RESULTS: After the first dose, the trend was for a greater decrease in glomerular filtration rate with naproxen (-5.31 mL/min per 1.73 m2) compared with celecoxib (-0.86 mL/min per 1.73 m2). The treatment difference became statistically significant on day 6 (-7.53 vs -1.11 mL/min per 1.73 m2 for naproxen and celecoxib, respectively; P=.004). Urinary prostaglandin E2 and 6-keto-prostaglandin F1alpha excretion was significantly reduced from baseline across the treatment interval with both celecoxib and naproxen (P< or =.04). There were no significant differences in prostaglandin excretion between these 2 agents (P> or =.07). Small, transient decreases (P<.05) in urinary sodium excretion were observed after the initiation of both celecoxib and naproxen treatment. Sodium excretion values returned to baseline by the end of the study. CONCLUSIONS: The results indicate that cyclooxygenase 2-specific inhibition in healthy elderly subjects may spare renal hemodynamic function, although the effects on sodium excretion, as well as urinary prostaglandin E2 and 6-keto-prostaglandin F1alpha excretion, appear to be similar to those of nonspecific cyclooxygenase inhibitors such as naproxen.

Ethics and professionalism education during neonatal-perinatal fellowship training in the United States.

OBJECTIVE: The objectives of this study were to determine the perceived adequacy of ethics and professionalism education for neonatal-perinatal fellows in the United States, and to measure confidence of fellows and recent graduates when navigating ethical issues. STUDY DESIGN: Neonatal-Perinatal Fellowship Directors, fellows and recent graduates were surveyed regarding the quality and type of such education during training, and perceived confidence of fellows/graduates in confronting ethical dilemmas. RESULT: Forty-six of 97 Directors (47%) and 82 of 444 fellows/graduates (18%) completed the surveys. Over 97% of respondents agreed that ethics training is 'important/very important'. Only 63% of Directors and 37% of fellows/graduates rated ethics education as 'excellent/very good' (P=0.004). While 96% of Directors reported teaching of ethics, only 70% of fellows/graduates reported such teaching (P<0.001). Teaching methods and their perceived effectiveness varied widely. CONCLUSION: Training in ethics and professionalism for fellows is important, yet currently insufficient; a more standardized curriculum may be beneficial to ensure that trainees achieve competency.

Fraud and abuse of government medical benefit programs by psychiatrists.

Government rosters of physicians suspended from the Medicare and Medicaid programs because of fraud and abuse indicate that psychiatrists form a disproportionately large segment of the total. Of the factors contributing to this situation, the most notable is that because psychiatrists charge for time rather than for services, they are more readily apprehended if they violate the rules. The authors speculate on whether in fact psychiatrists break the law more than physicians in other-specialties or whether the statistics are purely artifactual.

Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac.

It has been hypothesized that cyclooxygenase 2 specific inhibitors may increase the risk of cardiovascular (CV) thromboembolic events because of their inhibition of vascular prostacyclin synthesis and lack of an effect on platelet thromboxane A(2) production and aggregation. Thus, we analyzed the data for celecoxib and nonsteroidal anti-inflammatory drugs (NSAIDs) from the Celecoxib Long-term Arthritis Safety Study to determine the incidences of serious CV thromboembolic events. This trial included 3,987 persons randomized to celecoxib 400 mg twice daily (2,320 person-years of exposure) and 3,981 persons randomized to either ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily (2,203 person-years). Because acetylsalicylic acid (ASA) use for CV risk prophylaxis (< or =325 mg/day) was permitted, separate analyses were performed for all patients and those not taking ASA. The incidences of serious CV thromboembolic events (myocardial infarction, stroke, CV deaths, and peripheral events) were similar, and not significantly different, between celecoxib and NSAID comparators (combined or individually) for all patients as well as the subgroup of patients not taking ASA. This observation was true both for all serious CV thromboembolic events, as well as for individual events. No increase in myocardial infarction was apparent, even in patients not taking ASA who were candidates for secondary prophylaxis for myocardial infarction. The relative risks for celecoxib versus NSAIDs for serious CV thromboembolic events were 1.1 for all patients and 1.1 for the subgroup of patients not taking ASA (95% confidence interval 0.7 to 1.6 and 0.6 to 1.9, respectively). In addition, the incidences of adverse CV events such as hypertension, edema, and congestive heart failure were similar to, or significantly lower than, NSAID comparators regardless of the use of ASA. Thus, these analyses demonstrate no increased risk of serious CV thromboembolic events associated with celecoxib compared with conventional NSAIDs and therefore do not support the hypothesis of a class adverse effect of cyclooxygenase 2 specific inhibitors on the CV system.

Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with those of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), and placebo in the treatment of osteoarthritis of the knee. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 1003 patients with symptomatic osteoarthritis of the knee were randomly assigned to receive celecoxib at doses of 50, 100, or 200 mg twice a day; naproxen, 500 mg twice a day; or placebo for 12 weeks. Patients were evaluated with standard measures of efficacy 2 to 7 days after discontinuing previous NSAID or analgesic therapy and after 2, 6, and 12 weeks of treatment with the study drug. RESULTS: Celecoxib treatment led to significant improvement in the signs and symptoms of osteoarthritis as determined by all efficacy measures. Significant pain relief occurred within 2 days of the initiation of treatment, and maximum anti-inflammatory and analgesic activity, evident within 2 weeks, was sustained throughout the 12-week study. All celecoxib doses were efficacious compared with placebo, although the 50-mg twice-daily dosage regimen was minimally effective. The higher doses of celecoxib (100 and 200 mg twice a day) were similarly efficacious, and the magnitude of improvement observed with these dosing regimens was comparable to that seen with naproxen at a dose of 500 mg twice a day. All doses of celecoxib and naproxen were well tolerated. CONCLUSION: COX-2 inhibition with celecoxib is an effective approach for the treatment of osteoarthritis, as seen by clinical improvement in signs and symptoms comparable to treatment with naproxen.

Dyspepsia tolerability from the patients' perspective: a comparison of celecoxib with diclofenac.

AIM: To compare celecoxib (800 mg/day, n=1997) with diclofenac (150 mg/day, n=1996) on dyspepsia-related tolerability. METHODS: In one of the two protocols comprising the Celecoxib Long-Term Arthritis Safety Study, a randomized double-blind trial, patients completed the Severity of Dyspepsia Assessment Questionnaire at baseline and at weeks 4, 13, 26 and 52 for the following three scales: Pain Intensity, Non-Pain Symptoms and Satisfaction with Dyspepsia-Related Health. RESULTS: For the Pain Intensity scale, patients given diclofenac had significantly higher (worsening dyspepsia) mean changes, defined as follow-up minus baseline, than patients given celecoxib (P < 0.001, at all assessments). The mean changes in the Pain Intensity scale (scale, 2-47; higher score is higher pain intensity) were 0.99 (95% confidence interval (CI): 0.50, 1.48) for celecoxib and 2.76 (95% CI: 2.28, 3.25) for diclofenac at 4 weeks. Satisfaction was superior with celecoxib at all assessments (P < 0.001). At 4 weeks, the mean changes in the Satisfaction scale (scale, 7-35; higher score is higher satisfaction) were 0.02 (95% CI: - 0.26, 0.29) for celecoxib and - 0.72 (95% CI: - 1.00, - 0.45) for diclofenac. Diclofenac patients had significantly higher Non-Pain Symptoms at 4 weeks (P=0.005). CONCLUSIONS: Celecoxib, at two to four times the recommended dose, demonstrated a superior dyspepsia-related tolerability and satisfaction compared with standard dosages of diclofenac.

Celecoxib does not significantly alter the pharmacokinetics or hypoprothrombinemic effect of warfarin in healthy subjects.

The objective of this study was to determine the effects of celecoxib, an anti-inflammatory/analgesic agent that primarily inhibits COX-2 and not COX-1 at therapeutic doses, on the steady-state pharmacokinetic profile and hypoprothrombinemic effect of racemic warfarin in healthy volunteers. Twenty-four healthy adult volunteers on maintenance doses of racemic warfarin (2-5 mg daily), stabilized to prothrombin times (PT) 1.2 to 1.7 times pretreatment PT values for 3 consecutive days, were randomized to receive concomitant celecoxib (200 mg bid) or placebo for 7 days in an open-label, multiple-dose, randomized, placebo-controlled, parallel-group study of warfarin pharmacokinetics and PT. Steady-state exposure of S- and R-warfarin (area under the curve [AUC]) and maximum plasma concentration (Cmax) in subjects receiving celecoxib were within 2% to 8% of the warfarin AUC and Cmax in subjects receiving placebo during the concomitant treatment period. In addition, PT values were not significantly different in subjects receiving warfarin and celecoxib concomitantly compared with subjects receiving warfarin and placebo. In conclusion, concomitant administration of celecoxib has no significant effect on PT or steady-state pharmacokinetics of S- or R-warfarin in healthy volunteers.

Effects of celecoxib, a novel cyclooxygenase-2 inhibitor, on platelet function in healthy adults: a randomized, controlled trial.

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX-2 but spares COX-1 at therapeutic doses, is expected to have minimal effects on platelet function. A double-blind, randomized, placebo-controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A2 receptor agonist]), bleeding time, and serum thromboxane B2 (TxB2) level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB2 levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs.

Ultrastructure and biochemical studies of the flagellar sheath of Helicobacter pylori.

Helicobacter pylori flagellar sheaths were isolated by sucrose density-gradient centrifugation and analysed by electronmicroscopy, SDS-PAGE and gas-liquid chromatography. Electronmicroscopy of thin sections of flagella showed an internal electron-dense filament and a surrounding flagellar sheath with the typical bilayer structure of a membrane. The flagellar filaments could be disintegrated by acid treatment and the resulting isolated flagellar sheaths formed vesicles, sometimes with characteristic structures. Centrifugation of flagellar preparations after acid treatment resulted in the enrichment of flagellar sheaths in the pellet. SDS-PAGE analysis of the pellet showed a reduction of the flagellin band and a number of protein bands of 150, 76, 67, 65, 53, 51, 49, 29.5, 18, 17 and 16 kDa. However, there were no major protein bands characteristic for the sheath. Differences between the protein profiles of Sarkosyl-insoluble membranes and flagellar sheaths appeared in the lower M(r) range of 30-14 kDa. Major fatty acids of isolated flagellar sheaths were C 14:0, C 19:0 cyc, C 18:0, and the LPS-specific fatty acids 3-OH C 16:0 and 3-OH C 18:0. The results demonstrate that the flagellar sheaths of H. pylori are membranes and contain LPS and proteins.

An endoscopic study of gastroduodenal lesions induced by nonsteroidal anti-inflammatory drugs.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are an effective therapy for the pain and inflammation of arthritis, they are associated with serious side effects, particularly ulceration, bleeding, and perforation of the gastrointestinal (GI) tract. In this study, 1826 OA or RA patients who either had been taking NSAIDS for > or =6 months or had been unable to tolerate continuous NSAID use because of adverse GI symptoms or suspected NSAID-related gastroduodenal lesions were examined endoscopically for gastroduodenal lesions and ulcers. At the same time, the patients were asked to rate the severity of any GI symptoms they had been experiencing. Of the total number of patients studied, 817 (44.7%) were OA patients with a mean (+/- SD) age of 55.8+/-12.9 years, and 1009 (55.3%) were RA patients with a mean age of 53.1+/-13.1 years. Clinically significant gastroduodenal lesions were found in 37.1% of patients (n = 678); of these, 24.0% (n = 439) had ulcers. Gastric ulcers were more frequent than duodenal ulcers (14.8% vs 10.2% of patients; P < 0.05), and most gastric ulcers (72.0%) were found in the antrum of the stomach. The prevalence of gastroduodenal ulcers increased with age (P < 0.001), duration of OA (P < 0.001), and duration of current NSAID use (P = 0.019). The prevalence of gastroduodenal ulcers in patients taking NSAIDs for <1 year was 13.8%, compared with a nearly twofold higher prevalence (25.9%) in patients taking NSAIDs for periods of > or =1 year and up to 15 years. The prevalence of gastric ulcers was 32.6% in patients with a history of gastric ulcer but only 13.5% in patients with no GI history (previous gastric ulcer, duodenal ulcer, or upper GI hemorrhage). No relationship was found between the prevalence of gastroduodenal ulcers and sex (men, 22.4%; women, 24.9%) or prevalence of gastroduodenal ulcers and type of arthritic disease (RA, 23.6%; OA, 24.5%). The prevalence of gastroduodenal ulcers increased with the severity of GI symptoms (P = 0.007). These results provide further endoscopic confirmation of the association between NSAID use and gastroduodenal lesions and ulcers and support the contention that safer treatment alternatives to conventional NSAIDs are required.

Comparison of once-daily and twice-daily administration of celecoxib for the treatment of osteoarthritis of the knee.

OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of a celecoxib 200 mg QD regimen with a 100 mg BID regimen in patients with osteoarthritis (OA) of the knee. METHODS: Patients enrolled in this prospective, double-blind, placebo-controlled, parallel-group, multicenter study were randomly assigned to receive celecoxib 100 mg BID, celecoxib 200 mg QD, or placebo for 6 weeks. Assessments of OA severity (Patient's and Physician's Global Assessments of Arthritis, Patient's Assessment of Arthritis Pain-Visual Analog Scale, Lequesne Osteoarthritis Severity Index, and the Western Ontario and McMaster Universities Osteoarthritis Index) were performed at baseline and at week 2 and/or 6. Patients who discontinued treatment underwent assessments at the time of withdrawal from the study. RESULTS: Of the 718 patients enrolled, 243 received celecoxib 100 mg BID, 231 received celecoxib 200 mg QD, and 244 received placebo. For all measures of efficacy, at all assessments, improvements from baseline in both celecoxib groups were superior to that seen in the placebo group (P < 0.05). No significant differences in efficacy between the celecoxib groups were observed. The overall incidence of adverse events was similar in the 2 celecoxib treatment groups. CONCLUSIONS: Dosing regimens of celecoxib 200 mg QD and 100 mg BID are equally effective and well tolerated in patients with OA of the knee. The availability of 2 effective regimens provides patients and physicians with increased flexibility in the selection of an appropriate dosing regimen for celecoxib therapy.

Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults.

BACKGROUND: Current outpatient management of postoperative pain includes the use of oral opioid analgesics or nonsteroidal anti-inflammatory drugs; however, both types of medications are associated with side effects that can limit their usefulness in the outpatient setting. OBJECTIVE: Two studies with identical protocols assessed the single- and multiple-dose analgesic efficacy and tolerability of celecoxib, a specific cyclooxygenase-2 inhibitor, in the treatment of acute pain after orthopedic surgery. METHODS: These were multicenter, randomized, placebo- and active-controlled, double-blind, parallel-group trials conducted between January and June 1998. Both consisted of a single-dose assessment period (SDAP) and a multiple-dose assessment period (MDAP). In the SDAP, patients who had undergone orthopedic surgery received a single oral dose of celecoxib 200 mg, hydrocodone 10 mg/acetaminophen 1000 mg, or placebo within 24 hours after the end of anesthesia, with pain assessments conducted over the following 8-hour period. In the MDAP, extending from 8 hours after the first dose of study medication up to 5 days, patients who had received < or =1 dose of rescue medication during the SDAP continued on study medication (placebo recipients were rerandomized to active treatment), which could be taken up to 3 times a day as needed. RESULTS: A total of 418 patients were enrolled in the 2 trials. During the SDAP, 141 patients received celecoxib, 136 received hydrocodone/acetaminophen, and 141 received placebo. During the MDAP, 185 patients received celecoxib and 181 received hydrocodone/acetaminophen. When the combined data were analyzed, mean pain intensity difference (PID) scores generally favored the active treatments over placebo from 1 to 6 hours (with the exception of 1.5 hours) after dosing (P < or = 0.016) and favored celecoxib over the other treatments at 7 and 8 hours after dosing (P < 0.001). The active treatments demonstrated superior summed PID scores through 8 hours (P < 0.001), significantly shorter median times to onset of analgesia (P < 0.05), and significantly longer median times to first use of rescue medication (P < 0.05). During the MDAP, more hydrocodone/acetaminophen-treated patients (20%) than celecoxib-treated patients (12%) required rescue medication (P < 0.05), and the celecoxib group had significantly lower maximum pain intensity scores (P < 0.001, days 2-5), required fewer doses of study medication (P < or = 0.01, days 3-5), and had superior scores on a modified American Pain Society Patient Outcome Questionnaire (P < or = 0.013). In addition, a significantly lower proportion of celecoxib-treated patients experienced adverse events (43%) compared with hydrocodone/acetaminophen-treated patients (89%; P < 0.001). CONCLUSIONS: Over 8 hours, patients with moderate to severe pain after orthopedic surgery experienced comparable analgesia with single doses of celecoxib and hydrocodone/acetaminophen. Over a 5-day period, oral doses of celecoxib 200 mg taken 3 times a day demonstrated superior analgesia and tolerability compared with hydrocodone 10 mg/acetaminophen 1000 mg taken 3 times a day. Most patients required no more than 2 daily doses of celecoxib 200 mg for the control of their postorthopedic surgical pain.

Horseradish peroxidase localization of cardiac vagal preganglionic somata.

Cardiac vagal preganglionic somata were labeled in cats by the horseradish peroxidase (HRP) technique. The anatomical characteristics of cell bodies with axons in the left and right cervical vagi compared. HRP was injected subepicardially in three groups of pentobarbital anesthetized animals. In two test groups, injections were made after a left and right cervical vagotomy, respectively. In a control group, peripheral cardiac parasympathectomies were performed prior to HRP injection. The controls served to determine the number of somata labeled by HRP uptake via vagal fibers innervating viscera closely approximating the myocardium. After a 48 h survival period the cats were reanesthetized, perfused and fixed. Brain stems were removed, cut in the transverse or sagittal plane and developed with 3,3'-diaminobenzidine. Control cats had 6.8% the number of labeled cell bodies identified in animals with an intact vagus. Thus, few labeled somata in test cats were associated with noncardia tissue. The number, distribution and sizes of labeled cell bodies in test cats were similar. Somata were located ipsilateral to the intact vagus in three regions: the nucleus ambiguus (NA), the dorsal motor nucleus of the vagus (DMN) and an intermediate zone (IZ) between the NA and DMN. The NA contained the maximum number of cell bodies while successively fewer somata were located in the DMN and IZ. Somata of the NA were heterogeneously distributed along the longitudinal neuraxis. The region of maximal cell body concentration was between 1.0 and 1.8 mm rostral to the obex. Somata of the DMN and IZ were homogeneously and sparsely distributed along the neuraxis. The long and short axes of NA somata were larger than corresponding dimensions of cell bodies in the DMN or IZ. However, the dimensions of somata in the DMN and IZ were similar. The identification of labeled cell bodies in three medullary regions and the size differences of the somata in these regions may reflect a central physiological organization of cardia vagal somata.

Upper gastrointestinal tolerability of celecoxib compared with diclofenac in the treatment of osteoarthritis and rheumatoid arthritis.

OBJECTIVE: To compare the upper gastrointestinal (UGI) tolerability of celecoxib (a cyclooxygenase-2 specific inhibitor) and diclofenac using data from three randomised, double-blind clinical trials in osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Patients in two OA studies received either celecoxib 100 mg BID (n = 545), diclofenac 50 mg BID or TID (n = 540), or placebo (n = 200) for 6 weeks. In the RA study, patients received celecoxib 200 mg BID (n = 326) or diclofenac 75 mg BID (n = 329) for 24 weeks. The cumulative incidence of abdominal pain, dyspepsia, nausea or any of these events (UGI tolerability composite endpoint) after the first 6 weeks was estimated using time-to-event analysis. RESULTS: In the pooled OA trials, the cumulative incidence of the composite endpoint was significantly higher with diclofenac (17.6%; 95% CI: 14.4-20.9%) than celecoxib (11.1%; 95% CI: 8.4-13.8%; p = 0.002) and comparable with placebo (13.3%; 95% CI: 8.1-18.4%; p = 0.157). In the PA trial, the cumulative incidence of the UGI tolerability composite endpoint was also significantly higher with diclofenac (20.7%; 95% CI: 16.3-25.1%) than celecoxib (15.9%; 95% CI: 11.9-20.0%; p = 0.013). Celecoxib was also better tolerated than diclofenac in this trial in terms of the cumulative incidences of abdominal pain (p = 0.031) and dyspepsia (p = 0.062). The results of the UGI tolerability composite endpoint analysis were confirmed using the Cox proportional hazards model to controlfor other predictors of UGI adverse events. CONCLUSION: The UGI tolerability of therapeutic dosages of celecoxib was significantly better than diclofenac in patients with RA or OA.

The Amelia Stern syndrome: a diagnosis of a condition among female physicians?

Numerous studies have provided numerical portraits of some of the difficulties of women physicians at work in a field that traditionally has been the preserve of men. These studies, like much of recent feminist literature, often focus on the tension between maintaining a career and being a wife and mother. They usually provide aggregate data but fail to convey compellingly the nuances and emotions involved in the issues they address. Perri Klass's recent novel, Other Women's Children, the center point of this article, provides a case study of the thoughts and feelings attached to the issues addressed by the scientific inquiries. The book deals with the experiences of a woman pediatrician in a Boston hospital, a woman who uncertainly juggles her career and family responsibilities.

Selective vagal innervation of the heart.

Parasympathetic ganglia are imbedded (1) in the epicardial fat pad located on the posterior surface of the dog's heart and (2) immediately overlying the point of penetration by the coronary sinus into the interatrial septum. The fat pad is situated between the inferior vena cava and the inferior left atrium. It contains multiple encapsulated ganglia, each consisting of two to 80 separate cells, richly intermingled with neural elements. Destruction of these ganglia by surgical excision and/or phenol painting interrupts both right and left vagal inhibition of atrio-ventricular (A-V) conduction, without obviously altering vagal modulation of sinoatrial function. Excision or phenol destruction of the fat pad overlying the right pulmonary vein inlets to the left atrium interrupts both right and left vagal inhibition of sinoatrial function, again without interfering with vagal control of atrioventricular nodal function. Well organized, encapsulated autonomic ganglia are also found throughout this fat pad. These experiments thus identify and localize separate concentrations of ganglion cells which differentially modulate automaticity and A-V conduction in the canine heart.

Effect of Helicobacter pylori on dbc-AMP stimulated acid secretion by human parietal cells.

This study examines the effect of different H.p. strains (A-D) on dbc-AMP stimulated acid secretion by human parietal cells in vitro. H.p. strains A and D reduced acid secretion dose-dependently between 20 and 80%. In contrast, H.p. strains B and C had little or no effect. We conclude that H.p. strains vary in their ability to suppress acid secretion, and that the site of inhibition lies beyond the c-AMP level, possibly involving the K+H(+)-ATPase of the parietal cell. Interference with acid secretion may facilitate H.p. colonization of the stomach and may prove to be an important pathogenetic factor.

Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip.

Osteoarthritis (OA) is responsible for more disability of the lower extremities in the elderly than any other disease in the US. The pain associated with OA is the primary symptom leading to disability in these patients. Current ACR guidelines recommend consideration of acetaminophen for mild-to-moderate pain and conventional non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 specific inhibitors for moderate-to-severe OA symptoms. The aim of this study was to compare the efficacy and safety of the COX-1 sparing, COX-2 specific inhibitor, celecoxib, with the conventional NSAID naproxen, and placebo, in the treatment of OA of the hip. In this multicenter, randomized, placebo-controlled trial, 1061 patients with symptomatic OA of the hip were randomized to receive celecoxib at doses of 100 mg, 200 mg, or 400 mg/day; naproxen 1000 mg/day; or placebo, for 12 weeks. Patients were evaluated using standard measures of efficacy at baseline, 2-4 days after discontinuing previous NSAID or analgesic therapy, and after 2, 6, and 12 weeks of treatment. All doses of celecoxib and naproxen significantly improved the symptoms of OA, at all time points compared with placebo. This sustained treatment effect of celecoxib was dose dependent. In terms of pain relief and improvement in functional capacity, celecoxib 200 mg/day and 400 mg/day were similarly efficacious and were comparable to naproxen. Both drugs were generally well tolerated. Celecoxib at a dose of 200 mg/day is as effective as a standard therapeutic dose of the conventional NSAID, naproxen, in reducing the pain associated with OA of the hip.