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Biomedical subjects

J S Tan

Publications and source records attributed to J S Tan.

At least 37 records · Page 2Linked to original sources

Mutagenic synergy between paraoxon and mammalian or plant-activated aromatic amines.

Paraoxon (diethyl-p-nitrophenylphosphate) is the toxic, but non-mutagenic metabolite of the organophosphorus ester (OP) insecticide parathion. Although this agent has been used as a deacetylase inhibitor in many studies, we discovered a mutagenic synergy with paraoxon and plant-activated m-phenylenediamine or with direct-acting 2-acetoxyacetylaminofluorene in Salmonella typhimurium cells [Gichner T et al. (1996): Environ Mol Mutagen 27; 59-66]. In the present study, mammalian-activated m-phenylenediamine, o-phenylenediamine, p-phenylenediamine, benzidine, 2,3-diaminophenazine or 2-aminofluorene, as well as plant-activated benzidine or 2-aminofluorene expressed an elevated mutagenic potency when assayed with S. typhimurium strain YG1024 in the presence of paraoxon. Under non-toxic conditions, paraoxon amplified the S. typhimurium mutant yield induced by these aromatic amines between 1.9-fold and 8.4-fold. Spectrophotometric analysis demonstrated that the rate of degradation of 2-acetoxyacetylaminofluorene was not significantly different in phosphate buffer with or without paraoxon or with S. typhimurium cytosol with or without paraoxon. Also paraoxon-mediated mutagenic synergy does not appear to be due to a direct reaction with aromatic amines. Mutagenic synergy between aromatic amines and OP oxon products may be a cause of concern because people are chronically exposed to environmental and dietary aromatic amines, and a significant segment of the U.S. population tested positive for OP insecticide residues.

Acetoxyacetylaminofluorene↗

Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation?

We retrospectively evaluated the charts of 112 patients with diabetic foot infection to determine if early aggressive surgical intervention improves outcome. All patients were classified into two groups on the basis of the timing of surgical intervention and appropriate antimicrobial therapy. Group I included patients who underwent no surgical intervention during the first 3 days of hospitalization but received intravenous antimicrobial therapy, and group II included patients who underwent surgical intervention promptly and received intravenous antimicrobial therapy. Group II was further divided; group IIA included patients who underwent debridement, and group IIB included patients who underwent local limited amputation. A higher rate of patients in group I than in group II (27.6% vs. 13%, respectively; P < .01) required above-ankle amputation during the same hospitalization or subsequent admission. Overall, an aggressive surgical approach against foot infection in hospitalized diabetic patients reduced the need for above-ankle amputation and the length of hospital stay by at least 6 days. Treatment of diabetic foot infection requires the combination of early surgical treatment and antimicrobial therapy.

Adult↗

Community-acquired pneumonia. What's needed for accurate diagnosis.

Characteristic clinical findings of fever, cough, and rhonchi, together with a new infiltrate on chest films and documentation of a pathogen, establish a diagnosis of infectious pneumonia. Several factors have had an impact on the approach to diagnosis of community-acquired pneumonia by the primary care physician. These include the expanding number of possible pathogens as well as their increasing resistance to antimicrobial therapy. Although the clinical presentation may suggest a specific cause, findings often overlap too much for reliable identification of the specific agent on clinical grounds alone. Isolation of the microorganism or determination of the presence of a specific antigen or antibody is necessary. However, even after extensive studies are performed, the pathogen remains unidentified in 30% to 50% of cases. The primary care physician therefore needs to balance reasonable use of diagnostic tests with empirical therapy.

Humans↗

Management of staphylococcal and streptococcal infections.

Staphylococcus and streptococcus are bacteria commonly found on the skin and in the mucous membrane. These bacteria are frequently associated with mild cutaneous infections but may invade to cause deeper infections including necrotizing soft-tissue infections, sepsis with or without metastatic lesions, and immunologic or toxin associated sequelae. Early recognition and timely intervention are the hallmarks of appropriate management. Initial empiric therapy should be directed towards a broad spectrum of pathogens that include staphylococcus and streptococcus.

Anti-Bacterial Agents↗

Antipseudomonal penicillins.

Antipseudomonal penicillins retain most of the antibacterial activity of penicillin and aminopenicillins. This group of penicillins has added activities against many gram-negative rods, including P. aeruginosa. Similar to the earlier penicillins, this group continues to be susceptible to hydrolysis by many beta-lactamases and are, therefore, not consistently active against Staphylococcus, some gram-negative rods, and certain beta-lactamase-producing gram-negative anaerobes. The ureidopenicillins, especially piperacillin, appear to have better activity against Enterococcus, Klebsiella, and P. aeruginosa than ticarcillin. The advantages over the newer cephalosporins are (1) better activity against Enterococcus, (2) more consistent activity against Clostridium, and (3) more consistent synergy with aminoglycosides. The ureidopenicillins have certain advantages over carboxypenicillins, including lower sodium load, less frequent hypokalemia, reduced platelet dysfunction, minimal dosage adjustment in patients with renal failure, and a wider spectrum of antibacterial activity, especially against Enterococcus, Pseudomonas, and Klebsiella. The utility of the antipseudomonal penicillins by themselves is limited as agents for monotherapy when the infecting organism is not known. In addition, monotherapy is not recommended in certain infections to avoid the development of resistance. When combined with a beta-lactamase inhibitor or with an aminoglycoside, however, some of the weaknesses can be overcome.

Anti-Bacterial Agents↗

An outbreak of Pseudomonas aeruginosa ventilator-associated respiratory infections due to contaminated food coloring dye--further evidence of the significance of gastric colonization preceding nosocomial pneumonia.

An outbreak of ventilator-associated Pseudomonas aeruginosa respiratory infections in an intensive care unit of a teaching hospital was found to be associated with contaminated food coloring dye. Serotyping and bacteriocin typing indicated that the same strain of Pseudomonas was isolated from the food dye and from the respiratory cultures of the majority of patients. This observation lends credence to the importance of gastric colonization preceding pneumonia in ventilated patients.

Cross Infection↗

[Therapy of cantharides extract for perennial allergic rhinitis and its effect on total IgE in serum].

The therapy of 10% Cantharides extract in treating 50 cases of perennial allergic rhinitis (PAR) was studied. The extract was plastered and blistered on Dazhui, Neiguan point. It was observed by nasal mucosa provocative test, cells in nasal secretion test and serum total IgE test. The results showed that its effective rate was 88%, the allergic nasal mucosa provocative test of treated group alleviated obviously after the treatment (P < 0.01), the number of eosinophil and basophil in nasal secretion decreased (P < 0.01, P < 0.05); and the serum total IgE also reduced significantly (P < 0.01).

Acupuncture Points↗

Treatment of skin and soft-tissue infections.

Bacterial infections of the skin range from mild pyodermas to life-threatening necrotizing infections. Pyodermas are most often due to Staphylococcus aureus or beta-hemolytic Streptococcus sp, whereas infections associated with skin ulcers of the extremities, infections following trauma or surgery, and histotoxic necrotizing infections may involve a large number of additional pathogens, including Enterobacteriaceae, Pseudomonas sp, enterococci, and anaerobes. Management of bacterial skin and soft-tissue infections includes appropriate surgical drainage or excision of infected tissue and antimicrobial therapy. The combination of piperacillin and the beta-lactamase inhibitor tazobactam is a newly released antimicrobial, which has excellent in vitro activity against the vast majority of pathogens involved in skin infections. Two multicenter studies recently evaluated the efficacy and safety of piperacillin/tazobactam in the therapy of skin and soft-tissue infections in hospitalized patients. Piperacillin/tazobactam was well tolerated and demonstrated high clinical efficacy for the treatment of these infections.

Bacterial Infections↗

Hospital medical directors, quality of care, and financial returns.

You are a physician executive working very hard within a hospital on all sorts of medical staff issues and quality of care. You answer to the board. The latter, through its administrators, may still have difficulty documenting the precise value of a full-time physician executive. Your hospital is losing money or not making enough profit for capital expenditures and salary raises. It is considering or will have to consider staff cuts. What can you do that will influence the bottom line, produce a quality image, and quantify your value?

Financial Management, Hospital↗

Efficacy and safety of piperacillin/tazobactam in skin and soft tissue infections.

Piperacillin/tazobactam has excellent in vitro activity against the most pathogens involved in skin infections. Two large multicentre studies recently evaluated the efficacy and safety of piperacillin/tazobactam in the treatment of skin and soft tissue infections in patients in hospital. The efficacy and safety of piperacillin/tazobactam (4 g/500 mg every 8 hours) have been assessed in an open study in Europe. Among 120 evaluable patients, 93% were clinically cured or improved. Only six patients were withdrawn from the study because of side effects. In another trial, piperacillin/tazobactam were compared with ticarcillin/clavulanate in a double-blinded prospective study in the United States. Of evaluable patients, 67 received piperacillin/tazobactam (3 g/375 mg every 6 hours) and 44 received ticarcillin/clavulanate (3 g/100 mg every 6 hours). At assessment, 76% of patients given piperacillin/tazobactam and 77% of patients given ticarcillin/clavulanate had responded favourably. The lower success rate in this trial may be attributed to more stringent inclusion criteria that resulted in the incorporation of a higher proportion of patients with more severe conditions including diabetic/ischaemic foot infections. The incidence of adverse reactions was similar in both groups. Piperacillin/tazobactam seems to be both effective and safe in the treatment of skin and soft tissue infections in patients confined to hospital.

Bacterial Infections↗

Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats.

The biological fate of injected foreign particles is believed to be closely related to their interactions with blood plasma proteins and cells. In order to verify this correlation, we have quantitatively measured protein adsorption and blood retention profiles in rats by using model polystyrene latex nanoparticles. The in vitro interactions of these non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic polymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. Protein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chromatography and field-flow fractionation. Pluronic F108 and Tetronic 908 and 1508 copolymers (with PEO terminal block MWPEO > 5000, PPO middle block MWPPO > 3000, and HLB values > 24) were shown to be the most effective surface modifiers in reducing adsorption of plasma proteins on the particles. Minimum interaction of coated particles with whole blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these block copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surface characteristics provided by such amphiphilic surface modifiers.

Adsorption↗

Emergence of antimicrobial resistance in gram-negative bacilli causing bacteremia during therapy.

Treatment of serious infections caused by gram-negative bacilli with beta-lactam antimicrobial agents can induce Class I beta-lactamase production. This phenomenon can result in resistant microorganisms, and has been postulated to be a cause of therapeutic failure. The charts of patients bacteremic with Pseudomonas aeruginosa, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, and Providencia species (n = 120) during a 3-year period were reviewed to determine how common the emergence of resistance was, and to determine if in vitro susceptibility testing was a reliable therapeutic guide. Emergence of resistance was believed to occur when a subsequent bacteremic isolate showed at least a fourfold increase in minimum inhibitory concentration accompanied by a change of interpretive susceptibility category. In the group of patients who survived at least 48 hours that received beta-lactam therapy (n = 76), one case of emergence of resistance was identified (1.3%). Emergence of resistance to beta-lactam antimicrobial agents did not commonly cause therapeutic failure at our institution, and susceptibility testing of gram-negative bacilli by usual methods was a reliable guide to antimicrobial therapy.

Anti-Bacterial Agents↗

Treatment of hospitalized patients with complicated skin and skin structure infections: double-blind, randomized, multicenter study of piperacillin-tazobactam versus ticarcillin-clavulanate. The Piperacillin/Tazobactam Skin and Skin Structure Study Group.

We compared the efficacy and safety of two beta-lactam-beta-lactamase inhibitor combinations, namely, piperacillin-tazobactam and ticarcillin-clavulanate, in the treatment of complicated bacterial infections of skin that required hospitalization. The study was a randomized, double-blind, comparative trial involving 20 centers. The infections were classified as (i) cellulitis with drainage, (ii) cutaneous abscess, (iii) diabetic or ischemic foot infection, and (iv) infected wounds and ulcers with drainage. The clinical response rates were comparable for the two treatment regimens (61% of the patients were cured with piperacillin-tazobactam and ticarcillin-clavulanate and improvement was seen in 15 and 16% of patients treated with piperacillin-tazobactam and ticarcillin-clavulanate, respectively). Both regimens were found to be safe and well tolerated. These data support the use of piperacillin-tazobactam for initial empiric therapy of hospitalized patients with complicated skin and skin structure infections.

Bacteroides Infections↗

Community-acquired pneumonia. The changing picture.

Important changes in the initial management of community-acquired pneumonia have been prompted by the discovery of new respiratory pathogens, the changing susceptibility of traditional pathogens to antimicrobial agents, and the introduction of new antimicrobial agents. Although the clinical presentation may suggest a specific pathogen, findings overlap too much to reliably distinguish the specific cause of the pneumonia on a clinical basis. Useful laboratory studies include Gram's stain and culture of sputum, blood culture, serologic studies, and new tests such as the urinary antigen test for Legionella pneumophila. Empirical antimicrobial treatment must take into consideration that 20% to 30% of cases of community-acquired pneumonia are due to atypical pathogens that are not susceptible to beta-lactam agents.

Anti-Bacterial Agents↗

Pharmacokinetics of imipenem in serum and skin window fluid in healthy adults after intramuscular or intravenous administration.

The pharmacokinetic profiles of imipenem after intramuscular (i.m.) and intravenous injections were examined in adult volunteers. Levels of imipenem in serum after i.m. injection of a microcrystalline suspension of imipenem-cilastatin (500 mg each) reached a peak (8.0 micrograms/ml) at 1.5 h after administration, and concentrations were maintained in excess of 1.5 micrograms/ml for 6 h. Serum elimination half-life (1.3 h), volume of distribution (14.5 liters), and area under the curve (AUC; 27.8 micrograms.h/ml) after i.m. injection did not significantly differ from those of a comparable dose given by intravenous infusion. Bioavailability after i.m. injection was 89%. Imipenem levels in skin window fluid after i.m. administration were maximal (4.3 micrograms/ml) at 4 h after injection, at which time imipenem concentrations exceeded those produced by intravenous infusion. The AUCskin window/AUCserum ratio for skin window fluid after i.m. injection was 68%, indicating good penetration of the drug into skin fluid. This study shows that i.m. injection of 500 mg of imipenem-cilastatin results in concentrations of imipenem in serum and skin fluid that are, for at least 6 h, consistent with antimicrobial activity against susceptible organisms.

Adult↗

Treatment of bacteriuria in pregnancy.

The presence of bacteriuria during gestation increases the chance of acute pyelonephritis. Treatment of bacteriuria in pregnancy reduces subsequent development of symptomatic disease. Numerous studies have shown that single-dose therapy for asymptomatic bacteriuria is as effective as longer course of treatment. Single-dose therapy also has the advantages of improved compliance, reduced costs, and less adverse effects resulting from long term therapy. Follow-up cultures following antimicrobial treatment should be used for early detection of recurrence or relapse. If the urine culture yields no growth, a urine culture at a monthly interval will suffice. If on the other hand bacteriuria is present, a repeat course of antimicrobial therapy should be chosen based on antimicrobial susceptibility testing. A longer course of therapy, possibly with a different drug, is recommended for women with a positive follow-up urine culture. Acute cystitis may be treated with the same regimen as asymptomatic bacteriuria. When upper urinary tract infection is suspected, hospitalisation and a longer course of therapy is recommended. If the organism is susceptible to cefalexin or nitrofurantoin, postcoital prophylaxis with either agent for the remainder of the pregnancy may be beneficial.

Anti-Infective Agents↗

Results of total hip replacement in renal transplant recipients.

A vascular necrosis of the femoral head associated with steroid immunosuppression is a cause of significant morbidity in renal transplant recipients. We review the results of 30 total hip replacements in 20 renal transplant recipients with a mean follow-up of 6.3 years. The mean age at the time of surgery was 35 years. The average Hospital for Special Surgery Hip Score was 17 points before operation and 32 points after operation. Fourteen hips were rated excellent and 12 hips rated good. There were four failures--one hip was revised for symptomatic loosening and three prosthesis were removed for infection. Twenty-seven of the hip replacements were subjectively rated as satisfactory by the patient. There was no significant difference in post-operative hip scores between cemented and uncemented prostheses. Total hip replacement in renal transplant recipients in this study has shown good long term result with a revision rate of about 3%. Late infection was a major problem with an incidence of 13%. Prophylactic antibiotics must be used whenever there is a risk of haematogenous seeding from transient bacteremia in these immunosuppressed patients. Use of uncemented prosthesis may make future revision arthroplasty easier.

Adolescent↗