Co-regulation of {beta}-lactam resistance, alginate production and quorum sensing in Pseudomonas aeruginosa.

Development of ß-lactam resistance, production of alginate and modulation of virulence factor expression that alters host immune responses are the hallmarks of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. In this study, we propose that a co-regulatory network exists between these mechanisms. We compared the promoter activities of ampR, algT/U, lasR, lasI, rhlR, rhlI and lasA genes, representing the ß-lactam antibiotic resistance master regulatory gene, the alginate switch operon, the las and rhl quorum-sensing (QS) genes, and the LasA staphylolytic protease, respectively. Four isogenic P. aeruginosa strains, the prototypic Alg(-) PAO1, Alg(-) PAOampR, the mucoid Alg(+) PAOmucA22 (Alg(+) PDO300) and Alg(+) PAOmucA22ampR (Alg(+) PDOampR) were used. We found that in the presence of AmpR regulator and ß-lactam antibiotic, the extracytoplasmic function sigma factor AlgT/U positively regulated P(ampR), whereas AmpR negatively regulated P(algT/U). On the basis of this finding we suggest the presence of a negative feedback loop to limit algT/U expression. In addition, the functional AlgT/U caused a significant decrease in the expression of QS genes, whereas loss of ampR only resulted in increased P(lasI) and P(lasR) transcription. The upregulation of the las QS system is likely to be responsible for the increased lasA promoter and the LasA protease activities in Alg(-) PAOampR and Alg(+) PDOampR. The enhanced expression of virulence factors in the ampR strains correlated with a higher rate of Caenorhabditis elegans paralysis. Hence, this study shows that the loss of ampR results in increased virulence, and is indicative of the existence of a co-regulatory network between ß-lactam resistance, alginate production, QS and virulence factor production, with AmpR playing a central role.

Hypercalcemia-leukocytosis syndrome in a patient with cavitating squamous cell carcinoma of the lung.

INTRODUCTION: Lung cancer is the leading cause of death among the cancers seen in the United States. Hypercalcemia and leukocytosis are two common paraneoplastic syndromes associated with lung cancer. Unfortunately patients presenting with Hypercalcemia- leukocytosis syndrome has a worse prognosis than patients presenting with lung cancer alone. CASE PRESENTATION: We present a 67 yr old Caucasian male with a history of active smoking presenting as pneumonia being diagnosed as cavitating squamous cell carcinoma of the lung with hypercalcemia-leukocytosis syndrome CONCLUSION: There should be a high degree of suspicion to diagnose lung cancer in patients presenting with symptoms of paraneoplastic syndrome.

Hyperkalaemic paralysis presenting as ST-elevation myocardial infarction: a case report.

BACKGROUND: Hyperkalaemic paralysis due to renal failure is a rare but potentially life threatening event. CASE PRESENTATION: We present a patient who had sudden onset ascending flaccid paralysis. The EMS first diagnosis was acute ST-elevation myocardial infarction based on an EKG. In the emergency room (ER) due to careful history taking, serum electrolytes and repeat EKG a correct diagnosis was made and both hyperkalemia and paralysis were treated on time. CONCLUSION: Hyperkalaemic paralysis is rare. One must keep it in the back of the mind especially in the case of renal failure patients to avoid misdiagnosing a rapidly fatal but yet completely reversible condition.

Paravalvular mitral valve leakage presenting as congestive heart failure, missed by TTE but diagnosed by TEE: a case report.

BACKGROUND: Diagnosis of prosthetic valve leakage by the transthoracic echocardiogram (TTE) technique is more difficult. These limitations are diminished with the use of transesophageal echocardiogram (TEE) techniques. CASE REPORT: A 71 year old Caucasian male presented with symptoms and signs of congestive heart failure. Past medical history included a bio-prosthetic mitral valve replacement for severe mitral regurgitation. TTE showed possible mitral regurgitation. As the TTE did not correlate with the finding of a high E-velocity, a TEE was performed, which showed a significant paravalvular leak of moderate severity around the bio-prosthetic mitral valve. CONCLUSION: There should be a high degree of suspicion to diagnose a paravalvular leak.

Anterolateral papillary muscle rupture caused by myocardial infarction: A case report.

BACKGROUND: The rupture of the anterolateral papillary muscle is less common than the posteromedial papillary muscle since the anterolateral muscle has dual blood supplies, while the posteromedial papillary muscle has a single blood supply. CASE PRESENTATION: We present a case report of a 42 year old male presenting with heart failure being diagnosed to have mitral regurgitation from the partial rupture of the anterolateral papillary muscle due to coronary artery disease. The patient underwent a mitral valve replacement and concomitant coronary artery bypass grafting of the first and the second obtuse marginal arteries. CONCLUSION: Acute mitral regurgitation can be precipitated by acute myocardial infarction due to rupture of the anterolateral papillary muscle.

Isolated diffuse hyperplastic gastric polyposis presenting with severe anemia.

INTRODUCTION: Gastric polyps exist in a wide variety of types, most of which are small and often benign. Discovery of gastric polyps during Endoscopy necessitates biopsies. CASE PRESENTATION: We present a case report of an isolated diffuse hyperplastic gastric polyposis in a 26 years old Hispanic female when she was investigated for profound anemia. The Esophagogastroduodenoscopy revealed numerous gastric polyps filling the entire stomach. She was treated with near-total gastrectomy and her anemia resolved CONCLUSION: Isolated diffuse hyperplasic gastric polyposis with normal gastrin level is a rare entity and can present with severe anemia.

Non Hodgkin's lymphoma presenting with chest pain.

BACKGROUND: Non-Hodgkin's Lymphoma is a heterogeneous group of lymphoproliferative malignancies which can have differing patterns of behavior and clinical presentation. Unlike Hodgkin's disease, Non-Hodgkin's Lymphoma is much less predictable and has a far greater predilection for disseminating to extranodal sites. CASE REPORT: We offer a case of a 50 year old Caucasian male who presented with chest pain, and was ultimately diagnosed with follicular lymphoma by means of liver biopsy, in conjunction with immunohistochemistry. This malignancy grew at a rapid rate and over came our patient in a short period of time. The combination of a large tumor burden and cardiac infiltration made resuscitation extremely difficult when it became necessary, and this also made a positive outcome unlikely. CONCLUSIONS: It is rare for an immunocompetent patient to present with cardiac lymphoma without any previous signs and symptoms. Due to the rarity and the vague clinical presentation there must be a high degree of suspicion in order to diagnose cardiac lymphoma. As evidenced by this case time is of the essence to increase the likelyhood of survival in these patients.

Takotsubo cardiomyopathy in a 68-year old Russian female.

INTRODUCTION: Takotsubo cardiomyopathy also known as transient left ventricular apical ballooning, stress-induced cardiomyopathy can present with retrosternal chest pain with EKG changes that can mimic a myocardial infraction. CASE PRESENTATION: We present a 68 female with sudden onset retrosternal squeezing chest pain with positive cardiac enzymes and EKG changes suggestive of acute ST-elevation myocardial infraction. Patient was thrombolysed and cardiac cauterization done later showed normal coronaries with ballooning of the left ventricle apex. CONCLUSION: Takotsubo cardiomyopathy is a very rare disease entity yet can present to the emergency room as acute myocardial infraction.

Prescription errors and the impact of computerized prescription order entry system in a community-based hospital.

Adverse drug events occur often in hospitals. They can be prevented to a large extent by minimizing the human errors of prescription writing. To evaluate the efficacy of a computerized prescription order entry (CPOE) system with the help of ancillary support in minimizing prescription errors. Retrospective study carried out in a community-based urban teaching hospital in south Brooklyn, NY from January 2004 to January 2005. Errors were categorized into inappropriate dosage adjustment for creatinine clearance, duplication, incorrect orders, allergy verification, and incomplete orders. The pharmacists identified the type of error, the severity of error, the class of drug involved, and the department that made the error. A total of 466,311 prescriptions were entered in the period of 1 year. There were 3513 errors during this period (7.53 errors per 1000 prescriptions). More than half of these errors were made by the internal medicine specialty. In our study, 50% of the errors were severe errors (overdosing medications with narrow therapeutic index or over-riding allergies), 46.28% were moderate errors (overdosing, wrong dosing, duplicate orders, or prescribing multiple antibiotics), and 3.71% were not harmful errors (wrong dosing or incomplete orders). The errors were also categorized according to the class of medication. Errors in antibiotic prescription accounted for 53.9% of all errors. The pharmacist detected all these prescription errors as the prescriptions were reviewed in the CPOE system. Prescription errors are common medical errors seen in hospitals. The CPOE system has prevented and alerted the prescriber and pharmacist to dosage errors and allergies. Involvement of the pharmacist in reviewing the prescription and alerting the physician has minimized prescription errors to a great degree in our hospital setting. The incidence of prescription errors before the CPOE has been reported to range from 3 to 99 per 1000 prescriptions. The disparity could be due to the definition of medical errors, which has changed over the years, and also number of prescriptions included in the study and the study design.

Death within 48 hours of admission to the emergency department: the value of autopsy.

OBJECTIVE: To identify factors that contribute to patient death within 48 hours of admission to the emergency department. MATERIALS AND METHODS: A retrospective study of the patients who died within 48 hours of admission to the emergency department, from the years 2000 to 2003. The antemortem diagnosis and postmortem diagnosis were compared. RESULTS: A total of 189 autopsies were performed. The mean age at death for men (41.4 years) was lower than that for women (48.6) (p = 0.02). In both men and women, cardiac system involvement was the leading cause of death (27.5%), with myocardial infarction at 21.2%. The other common causes of death for both genders were blunt trauma (20.1%), intoxication with alcohol and/or other drugs (13.8%), penetrating trauma (gunshot or stab injuries) (13.2%), pulmonary thromboembolism (7.9%), and death caused by other respiratory causes (7.4%). Death caused by pulmonary thromboembolism was more common in women, whereas death caused by strokes, burns, and penetrating trauma were seen almost exclusively in men. CONCLUSIONS: Our study found a considerable concordance between the presumed antemortem cause of death and the postmortem findings. Although the mean age of death caused by myocardial infarction in our study was 52.45 years, MI caused a significant number of deaths among adults younger than 40 years of age.

Regression of grade III astrocytoma during the treatment of CML with imatinib mesylate.

Astrocytomas are central nervous system neoplasms, which are derived predominately from astrocytes. On the basis of the histopathologic characteristics astrocytomas are graded from I to IV. The cells that demonstrate the greatest degree of anaplasia are used to determine the histologic grade of the tumor. The mean age of survival are approximately 10 years from the time of diagnosis for pilocystic astrocytomas (World Health Organization grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2 to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV). The treatment is a combination of surgery, radiation, and chemotherapy depending of the grade of astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of his chronic myelogenous leukemia treatment failing to show recurrence of the astrocytoma 10 years after standard treatment for astrocytoma.

Infective endocarditis of native valve after anterior nasal packing.

We present a case report of a patient who was previously treated for spontaneous epistaxis with a petroleum jelly gauze (0.5 in x 72 in) anterior nasal packing filled with an antibiotic ointment, along with prophylactic oral clindamycin. The patient presented with fever and hypotension 3 days after the nasal packing. Her blood cultures grew methicillin-resistant Staphylococcus aureus and the transesophageal echocardiography showed vegetation on the atrial surface of the posterior mitral valve leaflet, confirming the diagnosis of bacterial endocarditis attributable to nasal packing. Several case reports discuss toxic shock syndrome after nasal packing, but none describe endocarditis of the native heart valves subsequent to anterior nasal packing. Current guidelines on endocarditis prophylaxis produced by the American Heart Association, European Cardiac Society, and British Cardiac Society together with published evidence do not recommend endocarditis prophylaxis for patients with native heart valves undergoing anterior nasal packing.

Pseudomonas aeruginosa AmpR is a global transcriptional factor that regulates expression of AmpC and PoxB beta-lactamases, proteases, quorum sensing, and other virulence factors.

In members of the family Enterobacteriaceae, ampC, which encodes a beta-lactamase, is regulated by an upstream, divergently transcribed gene, ampR. However, in Pseudomonas aeruginosa, the regulation of ampC is not understood. In this study, we compared the characteristics of a P. aeruginosa ampR mutant, PAOampR, with that of an isogenic ampR+ parent. The ampR mutation greatly altered AmpC production. In the absence of antibiotic, PAOampR expressed increased basal beta-lactamase levels. However, this increase was not followed by a concomitant increase in the P(ampC) promoter activity. The discrepancy in protein and transcription analyses led us to discover the presence of another chromosomal AmpR-regulated beta-lactamase, PoxB. We found that the expression of P. aeruginosa ampR greatly altered the beta-lactamase production from ampC and poxB in Escherichia coli: it up-regulated AmpC but down-regulated PoxB activities. In addition, the constitutive P(ampR) promoter activity in PAOampR indicated that AmpR did not autoregulate in the absence or presence of inducers. We further demonstrated that AmpR is a global regulator because the strain carrying the ampR mutation produced higher levels of pyocyanin and LasA protease and lower levels of LasB elastase than the wild-type strain. The increase in LasA levels was positively correlated with the P(lasA), P(lasI), and P(lasR) expression. The reduction in the LasB activity was positively correlated with the P(rhlR) expression. Thus, AmpR plays a dual role, positively regulating the ampC, lasB, and rhlR expression levels and negatively regulating the poxB, lasA, lasI, and lasR expression levels.

Characterization of poxB, a chromosomal-encoded Pseudomonas aeruginosa oxacillinase.

Pseudomonas aeruginosa is the major pathogen associated with morbidity and mortality of patients with cystic fibrosis. One of the reasons for the failure of beta-lactam antibiotic regimens appears to be mediated by de-regulation of the ampC gene, encoding the chromosomal Ambler's Class C beta-lactamase. Currently, the AmpC is the only known chromosomal beta-lactamase whose expression is regulated by a transcriptional regulator, AmpR. We generated an ampC mutation in the prototypic P. aeruginosa strain PAO1. The mutation in ampC did not abolish the beta-lactamase activity entirely suggesting the expression of yet another unreported beta-lactamase. Our genomic analysis revealed the presence of an open reading frame encoding a protein with high homology to the Class D beta-lactamases, commonly known as oxacillinases. The gene was named poxB for Pseudomonas oxacillinase. Cloning and expression of poxB in Escherichia coli conferred beta-lactam resistance to the host. We detected the presence of poxB both in clinical and environmental isolates. Our studies show that P. aeruginosa possesses two beta-lactamases, AmpC and PoxB, which contribute to its resistance against a wide spectrum of beta-lactam antibiotics.