Predicting methicillin resistance among community-onset Staphylococcus aureus bacteremia patients with prior healthcare-associated exposure.

To develop and validate prediction rules to identify the risk of methicillin-resistant Staphylococcus aureus (MRSA) infection among community patients who have healthcare-associated (HA) exposure and S. aureus bacteremia. A total of 1,166 adults with community-onset S. aureus bacteremia were retrospectively enrolled. The background prevalence of community MRSA infection was extrapolated from 392 community-associated S. aureus bacteremia (CA-SAB) patients without HA exposure. Complete and clinical risk scores were derived and tested using data from 774 healthcare-associated S. aureus bacteremia (HA-SAB) patients. The risk scores were modeled with and without incorporating previous microbiological data as a model predictor and stratified patients to low-, intermediate-, and high-risk groups for MRSA infection. The clinical risk score included five independent predictors and the complete risk score included six independent predictors. The clinical and complete risk scores stratified 32.7 % and 42.0 % of HA-SAB patients to the low-risk group for MRSA infection respectively. The prevalence of MRSA infection in score-stratified low-risk groups ranged from 16.3 % to 23.3 %, comparable to that of CA-SAB patients (13.8 %). Simple decision rules allow physicians to stratify the risk of MRSA infection when treating community patients with prior HA exposure and possible S. aureus infection.

Acute cholinergic syndrome following ingestion of contaminated herbal extract.

Herbal preparations are becoming more and more popular and increasingly used in the USA. Herbs are from natural plants and therefore often considered to be harmless compared with western medicines. Nevertheless, as the use of herbal remedies has risen, so has the incidence of acute and chronic herbal intoxication. The case history is presented of a 68-year-old man who presented with an acute cholinergic syndrome soon after ingesting a herbal preparation containing Flemingia macrophylla and ginseng. His red blood cell acetylcholinesterase activity dropped to 50% of the normal reference range. He was treated successfully with atropine and supportive care. It was thought that contamination with pesticides, such as organophosphate residue, was the probable cause. This case highlights the need to be more aware of the possibility of acute pesticide intoxication in herbal users, even when only small amounts are consumed.

Candida tropicalis-associated bilateral renal papillary necrosis and emphysematous pyelonephritis.

Although the kidney is often involved in disseminated and localized candidiasis, bilateral emphysematous pyelonephritis (EPN) is infrequently reported. Renal papillary necrosis (RPN) caused by fungi is also rare. We describe a patient with bilateral RPN and EPN caused by Candida tropicalis, who suffered from recurrent hematuria, flank pain, acute fulminant renal failure, and obstruction by a sloughed papilla. He was treated successfully with antifungal therapy and percutaneous nephrostomy (PCN). This is the first case report of C. tropicalis-associated EPN and RPN.

Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo.

BACKGROUND: Peritoneal fibrosis (PF) is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Proliferation of human peritoneal mesothelial cells (HPMC) and matrix over-production are regarded as the main processes predisposing to PF. Dipyridamole (DP) has been reported to have potential as an antiproliferative and antifibrotic agent. We thus investigated the effect of DP in inhibiting proliferation and collagen synthesis of HPMC. A rat model of peritonitis-induced PF was also established to demonstrate the in vivo preventive effect of DP. METHODS: HPMC was cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay. Intracellular cAMP was measured using an enzyme immunoassay (EIA) kit. Total collagen synthesis was measured by (3)H-proline incorporation assay. Expression of collagen alpha1 (I) and collagen alpha 1 (III) mRNAs was determined by Northern blotting. The rat model of peritonitis-induced PF was developed by adding dextran microbeads (Cytodex, 8 mg/1 mL volume) to a standardized suspension (3 x 10(9)) of Staphylococcus aureus. DP was administrated via intravenous infusion (4 mg in 1 h) daily for seven days. Macroscopic grading of intraperitoneal adhesions and histological analyses of peritoneal thickness and collagen expression were performed. RESULTS: Addition of DP to HPMC cultures suppressed serum-stimulated cell proliferation and collagen synthesis. The antimitogenic and antifibrotic effects of DP appear to be predominantly mediated through the cAMP pathway, as DP increased intracellular cAMP in a dose-dependent manner. The macroscopic grade of intraperitoneal adhesion and peritoneal thickness were both significantly increased in animals treated with Cytodex plus S. aureus; on the other hand, DP attenuated these fibrotic changes with statistical significance (P < 0.01). Analysis of gene expression of collagen alpha 1 (I) and alpha1 (III) in the peritoneal tissue of experimental animals yielded similar results. CONCLUSIONS: This study suggests that dipyridamole may have therapeutic potential in treating peritoneal fibrosis.

Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta.

BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.

ED overcrowding in Taiwan: facts and strategies.

The objective of this study was to quantity the extent of emergency department (ED) overcrowding in Taiwan and to identify possible solutions. The ED log was reviewed for all patients who presented to the National Taiwan University Hospital's ED from January 16, 1996 through February 15, 1996. Charts from patients held longer than 72 hours were reviewed. Among 5,810 patients, 213 (3.6%) were held in the ED for more than 72 hours (7.1 patients per day). In 149 (70.0%) of them, admission was indicated but delayed (42 because more than one subspecialty were involved, 57 because of unavailability of bed, and 50 because of the disparity in admission priority between the emergency physicians and house staffs). Eighteen (8.4%) patients did not meet admission criteria (13 could have been treated in outpatient clinics, 3 needed placement in nursing homes, 2 because of personal problems). The others (22%) recovered while waiting. Significant overcrowding exists in EDs in Taiwan. Four solutions are proposed: (1) creation of a holding unit; (2) flexible ward assignment; (3) pre-established rules for admission priority-setting; and (4) active interfacility transfer. Only through these efforts can EDs in Taiwan guarantee an optimal level of care in the face of a growing patient demand.

Pharmacologic agents inhibit rat mesangial cell proliferation and collagen synthesis.

Prevention of the development of end-stage renal disease is one of the most promising areas of research in nephrology. Because mesangial cell proliferation and extracellular matrix accumulation have been regarded as antecedents of glomerulosclerosis, agents that can inhibit mesangial cell proliferation may have a potential to retard the progression of renal diseases. Therefore, we investigated several clinically available agents that might affect mesangial cell proliferation and collagen synthesis in male Sprague-Dawley rats. Cell proliferation was measured by the tetrazolium dye uptake method. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. Our results showed that hydralazine (82% inhibition at 10 micrograms/mL), ticlopidine (61% inhibition at 30 micrograms/mL), aminophylline (66% inhibition at 200 micrograms/mL), and nicametate (91% inhibition at 1 mg/mL) inhibited serum-stimulated rat mesangial cell (RMC) growth in a dose-dependent manner. Ticlopidine (43% inhibition at 30 mg/mL), aminophylline (52% inhibition at 200 mg/mL), and nicametate (35% inhibition at 1 mg/mL) inhibited collagen synthesis in confluent RMCs. Aminophylline may act through increasing intracellular cAMP levels (9.7 +/- 0.7 pmol/mg protein at 200 micrograms/mL of aminophylline vs 4.2 +/- 0.6 pmol/mg protein at control). These data suggest that aminophylline, ticlopidine, hydralazine, and nicametate can inhibit RMC proliferation and collagen synthesis.

Extracellular matrix proteins modulate human peritoneal mesothelial cell behavior.

Human peritoneal mesothelial cells lie on a basement membrane-like material consisting of fibronectin (FN), type I collagen (CI), type III collagen (CIII) and laminin (LA). To understand how these extracellular matrix (ECM) proteins affect mesothelial cell behavior, we investigated their effect on the adhesion and proliferation of mesothelial cells. A modified methyltetrazolium dye method was used to assess cell number. The results showed that FN, CI, CIII and LA, all increased adhesion of mesothelial cells. The adhesive effect was blocked dose-dependently by a synthetic Arg-Gly-Asp-containing (RGD) peptide. When coated as a substratum (immobilized form), FN, CI, CIII and LA, all enhanced serum-stimulated and epidermal-growth-factor-stimulated cellular proliferation as compared with bovine-serum-albumin-blocked plastic surfaces. When added in a soluble form, all matrix proteins except FN inhibited serum-stimulated and epidermal-growth-factor-stimulated cellular proliferation at high concentrations (CI and CIII: 1-10 micrograms/ml, LA: 3-10 micrograms/ml). We conclude that peritoneal mesothelial cells possess an RGD-sensitive receptor and that the ECM can modulate adhesion and proliferation of peritoneal mesothelial cells. The growth-modulating effect depends on the form and concentration of the ECM proteins.

Hydralazine inhibits human peritoneal mesothelial cell proliferation and collagen synthesis.

The integrity of the mesothelial layer is essential for both defence and solute transport in continuous ambulatory peritoneal dialysis (CAPD). The human peritoneal mesothelial cell (HPMC) culture has been shown to be a very useful tool to study the peritoneal mesothelial stem cell behaviour. We investigated whether hydralazine, an antihypertensive agent frequently used, might affect HPMC growth and collagen synthesis. HPMCs were cultured from specimens of human omentum by enzymatic disaggregation of omentum. HPMC growth was evaluated by modified methyltetrazolium (MTT) assay. Cell viability was confirmed by trypan blue exclusion and lactate dehydrogenase assay. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. The procollagen alpha 1 (I) mRNA expression was evaluated by Northern blot analysis. Hydralazine inhibited serum-stimulated HPMC growth in a dose-dependent manner. The maximal inhibition was 93% at a concentration of 100 micrograms/ml. Hydralazine inhibited collagen synthesis in confluent mesothelial cells (47% inhibition at a concentration of 100 micrograms/ml). The procollagen alpha 1 (I) mRNA expression was also decreased by hydralazine (about 50% decrease at 100 micrograms/ml). These effects may be due to the phosphodiesterase inhibition property of hydralazine to increase intracellular cAMP levels. These data suggest that the use of hydralazine in CAPD patients may affect peritoneal membrane function and integrity.

Idiopathic pulmonary artery aneurysm.

The purpose of this article is to report two cases of pulmonary artery (PA) aneurysm in patients who had no evidence of left-to-right intracardiac shunting or other known relevant etiologies. One patient, a 52-year-old woman, was admitted to the hospital due to exertional palpitation, while the other patient, a 73-year-old woman, came to the hospital because of fever and cough. In both women, chest radiographic findings of a hugely dilated PA were confirmed by computed tomography (CT). In both cases, a ventriculogram showed fusiform dilatation of the main PA without evidence of pulmonary valve stenosis. The results of chest radiography, two-dimensional echocardiography, CT of the thorax, including pulmonary angiography in one patient, were compatible with the diagnosis of PA aneurysm. No specific drug regimen was administered nor was any surgical intervention performed in either patient. Both patients were asymptomatic as of the last telephone follow-up. Idiopathic PA aneurysm is a benign condition with better survival than PA aneurysms of other etiologies, because of the absence of left-to-right intracardiac shunting and significant pulmonary hypertension. PA aneurysm must be considered as part of the differential diagnosis in an enlarged pulmonary trunk seen on chest radiogram, and two-dimensional echocardiography should be performed initially.

Effects of intraperitoneal antibiotics on human peritoneal mesothelial cell growth.

Peritonitis is one of the most frequent complications of continuous ambulatory peritoneal dialysis (CAPD). Necrosis and exfoliation of the mesothelial cell layer of the peritoneum develop during the acute phase of peritonitis. Agents that hamper regeneration of mesothelial cells will cause delayed recovery of the peritoneal surface, which results in continuous exposure of underlying stem cells to the stimulation of growth factors and possibly leads to peritoneal fibrosis syndrome. The aim of the present study is to determine the effects of several intraperitoneal antibiotics on human peritoneal mesothelial cell (HPMC) growth at their usual loading and maintenance doses. HPMCs were isolated from human omenta. Proliferation of HPMC was evaluated by modified methyltetrazolium assay and cell membrane integrity was assessed by lactate dehydrogenase method. The results showed that most cephalosporins exert an inhibitory, even toxic, effect on HPMCs at their loading doses. Cephalothin, cephradine, cefamandole, cefoxitin, cefuroxime and cefoperazone inhibited HPMC proliferation at their maintenance doses. Vancomycin, clindamycin, aztreonam, piperacillin, imipenem, tobramycin and ceftriaxone have no effect in their usual intraperitoneal doses. From the viewpoint of peritoneal protection, not only drug sensitivity of the causative microorganisms but also effects of antibiotics on HPMC regeneration should be considered when selecting antibiotics for CAPD peritonitis.

Erythromycin-induced acute pancreatitis.

BACKGROUND: Pancreatitis due to ingestion of erythromycin is rare. CASE REPORT: A 20-year-old woman took erythromycin 3 g and acetaminophen 6 g before a tooth extraction. Forty minutes later, she experienced severe abdominal pain, nausea, and vomiting. The serum amylase and lipase were elevated. She recovered from the pancreatitis without sequelae after supportive treatment. CONCLUSION: This is the fourth reported case of erythromycin-induced acute pancreatitis in the English literature.

Pacemaker twiddler's syndrome: report of a case.

A patient with symptomatic atrioventricular blockage who had been treated by permanent pacemaker implantation, developed twiddler's syndrome 16 days after implantation. The electrode lead to the pacemaker pocket had been completely displaced, with the electrode tip having moved to the outside of the subclavian vein. Complete atrioventricular block was demonstrated by electrocardiogram. Reimplantation of the same electrode at the apex of the right ventricle relieved the symptoms. The patient is regularly followed up at an outpatient clinic and continues to be well. Although twiddler's syndrome is a rare complication of pacemaker implantation, preventive measures should be undertaken especially for those judged to be at high risk.

Effect of intraperitoneally administered agents on human peritoneal mesothelial cell growth.

During continuous ambulatory peritoneal dialysis, the peritoneal mesothelial cell layer is under continuous sloughing and regeneration processes. Agents unfavorable for mesothelial cell growth may be harmful to the peritoneal membrane. We investigated whether frequent intraperitoneally instilled agents affect mesothelial cell growth. Peritoneal mesothelial cells were cultured from the human omentum. The proliferation was assessed by using a modified methyltetrazolium assay and confirmed by Coulter cell counting. The results showed that a high-glucose medium and heparin inhibited mesothelial cell growth. Cephalothin at the usual intraperitoneal loading and maintenance doses is toxic to mesothelial cells. Ceftazidime is toxic to mesothelial cells at its loading dose and inhibits growth at its maintenance dose. Aminoglycosides including netilmicin, gentamicin, and amikacin all had inhibitory effects at the loading and maintenance dose ranges. Vancomycin had no effect. The usual combinations of heparin and cephalothin with netilmicin or gentamicin as the initial treatment regimen for bacterial peritonitis are toxic to mesothelial cells. These results suggest that some intraperitoneal agents potentially may hamper mesothelial cell regeneration. The judicious use of heparin and the proper choice of antibiotic combinations may be warranted from the point of view of peritoneal protection.

Correlation between renin responsiveness to furosemide and antihypertensive effect of captopril in patients with normal-renin essential hypertension.

The relationship between renin responsiveness to furosemide and the antihypertensive effect of captopril in patients with normal-renin essential hypertension were studied in 23 patients including nine men (mean age, 41 years) and 14 women (mean age, 40 years). Those who had an increment of more than 50% in plasma renin activity (PRA) two hours after an intravenous injection of 20 mg furosemide were classified as group A (n = 13) and the others were classified as group B (n = 10). Baseline PRA, plasma aldosterone and mean blood pressure (MBP) were not different between the two groups. Both groups showed no significant difference in natriuresis following furosemide administration. Significant change in MBP was observed after an oral dose of 100 mg captopril within four hours in group A, but not in group B. These data suggest that renin responsiveness to a single intravenous dose of furosemide can be a useful test for predicting the therapeutic response to captopril in patients with normal-renin essential hypertension. The furosemide test had a sensitivity of 75%, a specificity of 64%, a positive predictive value of 69% and a negative predictive value of 70%.