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Biomedical subjects

S M Palmer

Publications and source records attributed to S M Palmer.

At least 19 recordsLinked to original sources
PubMed1998

Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension associated with fibrotic occlusion of the smaller pulmonary veins. Although vasodilator therapy is effective in many patients with primary pulmonary hypertension, the role of vasodilators in PVOD is unclear because of concerns about precipitating pulmonary edema. Recently, however, there have been reports of successful therapy with oral vasodilators or intravenous administration of prostacyclin in patients with PVOD. In contrast, a patient with PVOD is described who developed acute pulmonary edema and respiratory failure during low-dose prostacyclin infusion, leading to death. This report suggests that vasodilators, especially prostacyclin, must be used with extreme caution in patients with known PVOD.

Adult↗
PubMed1997

Sarcoidosis.

Explore the source record for details and available documents.

Humans↗
PubMed1997

A case of disseminated infection with Nocardia brasiliensis in a lung transplant recipient.

BACKGROUND: Infection with Nocardia species is an increasingly recognized complication of solid organ transplantation. Nocardia asteroides accounts for most transplant-related nocardiosis, while Nocardia brasiliensis rarely causes infection in organ transplant recipients. METHODS: We describe a case of disseminated infection with N brasiliensis in a single-lung transplant recipient who also had concomitant infections with viral and fungal organisms. RESULTS: Although the mortality rate is high in immunocompromised patients with disseminated Nocardia infection, our patient responded favorably to prolonged antimicrobial therapy. CONCLUSIONS: This case illustrates that N brasiliensis, like N asteroides, produces pulmonary disease and dissemination in solid organ transplant recipients, and demonstrates the utility of prolonged treatment with trimethoprim-sulfamethoxazole in Nocardia infections.

Biopsy↗
PubMed1997

An evaluation of the bactericidal activity of ampicillin/sulbactam, piperacillin/tazobactam, imipenem or nafcillin alone and in combination with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in time-kill curves with infected fibrin clots.

The activity of piperacillin/tazobactam, ampicillin/sulbactam, imipenem and nafcillin alone and in combination with vancomycin was compared with vancomycin monotherapy against MRSA in test-tube time-kill studies and in infected fibrin clots. Bactericidal activity was achieved with all regimens except nafcillin monotherapy in test tubes but only with imipenem/vancomycin and nafcillin/vancomycin in fibrin clots infected with heterogeneous strains. No regimen was effective against the homogeneous strain. These agents may have potential as alternatives to vancomycin in selected infections.

Ampicillin↗
PubMed1996

Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections.

Ten patients were treated with conventional dosing (CD) and continuous-infusion (CI) vancomycin therapy in this prospective, randomized, crossover study. Patients were randomized to receive either CD or CI therapy for 2 consecutive days and then crossed over to receive the opposite regimen for 2 days. CD therapy consisted of 1 g of vancomycin every 12 h. CI therapy consisted of a 500-mg loading dose followed by 2 g infused over 24 h. Ten serum samples were obtained on the second day of each therapy for pharmacokinetic and pharmacodynamic analyses. Two clinical isolates of Staphylococcus aureus, one methicillin sensitive (MSSA 1199) and one methicillin resistant (MRSA 494), were chosen for pharmacodynamic evaluation of both regimens. The patient demographics (means +/- standard deviations [SD]) were as follows: sex, six males, four females; age, 36 +/- 11 years; and serum creatinine, 0.72 +/- 0.18 mg/dl. Mean pharmacokinetic parameters +/- SD for CD therapy were as follows: elimination rate constant, 0.16 +/- 0.07 h-1; half-life, 5.6 +/- 3.5 h; volume of distribution, 33.7 +/- 25 liters, 0.5 +/- 0.2 liters/kg; maximum concentration in serum, 53.4 +/- 19.3 micrograms/ml; and minimum concentration, 8.4 +/- 5.9 micrograms/ml. The steady-state concentration for CI was 20.2 +/- 11.1 micrograms/ml. Overall, both regimens resulted in the MIC being exceeded 100% of the time. The mean CD trough serum bactericidal titer (SBT) was 1:8, and the average CI SBTs were 1:16 for both isolates. Even though there was no statistically significant difference between CD trough and CI SBTs, the CI SBTs remained > 1:8 for 100% of the time versus 60% of the time for CD therapy. During CI therapy, 20 and 40% of the patients maintained SBTs of > 1:32 throughout the dosing interval for MSSA 1199 and MRSA 494, respectively. During CD therapy, however, only 10% of patients maintained SBTs of > 1:32 during the entire dosing interval for both isolates. The mean areas under the bactericidal titer-time curve (AUBC24s) +/- SD for MSSA 1199 were 528 +/- 263 for CD therapy and 547 +/- 390 for CI therapy. The mean AUBC24s +/- SD against MRSA 494 were 531 +/- 247 for CD and 548 +/- 293 for CI therapy. Similar to the AUBC24, the mean area under the concentration-time curve for a 24-h dosing interval divided by the MIC (AUC/MIC24) ratios +/- SD were 550.0 +/- 265.7 for CD and 552.6 +/- 373.4 for CI therapy, respectively. No statistically significant differences were found between any of the pharmacodynamic parameters for CD and CI therapy. In addition, no adverse effects with either CD or CI therapy were observed during the study. We conclude that CI and CD vancomycin therapy demonstrated equivalent pharmacodynamic activities. Although CI therapy was more likely to result in SBTs that remained above 1:8 for the entire regimen, the clinical impact of this result is unknown. Serum drug concentration variability was observed with both treatment regimens but to a lesser extent with CI administration. CI administration of vancomycin should be further evaluated to determine the clinical utility of this method of administration.

Adult↗
PubMed1996

Pharmacodynamics of once- or twice-daily levofloxacin versus vancomycin, with or without rifampin, against Staphylococcus aureus in an in vitro model with infected platelet-fibrin clots.

We compared the pharmacodynamic activities of levofloxacin versus vancomycin, with or without rifampin, in an in vitro model with infected platelet-fibrin clots simulating vegetations. Infected platelet-fibrin clots were prepared with human cryoprecipitate, human platelets, calcium, thrombin, and approximately 10(9) CFU of organisms (MSSA 1199 and MRSA 494) per g and then were suspended via monofilament line into the in vitro model containing Mueller-Hinton growth medium. Antibiotics were administered by bolus injection into the model to simulate human pharmacokinetics; the regimens simulated included levofloxacin at dosages of 800 mg every 24 h (q24h) and 400 mg q12h, vancomycin at 1 g q12h, and rifampin at 600 mg q24h. Each model was run in duplicate over a 72-h period. Infected platelet-fibrin clots were removed in duplicate from each model, weighed, homogenized, serially diluted with sterile 0.9% saline, and plated on tryptic soy agar plates and plates containing antibiotics at 3, 6, and 12 times the MIC to evaluate the emergence of resistance. Time-kill curves were constructed by plotting the inoculum size versus time. Residual inoculum at 72 h was used to compare regimens. All levofloxacin regimens were significantly better than vancomycin monotherapy against both isolates (P < 0.002). Against MSSA 1199, levofloxacin q24h was significantly better than all other regimens, including levofloxacin q12h (P < 0.002); however, no difference between the levofloxacin monotherapy and combination therapy (with rifampin) regimens against MRSA 494 was seen. Killing activity for levofloxacin appeared to correlate better with the peak/MIC ratio than with the area under the curve/MIC ratio. The addition of rifampin significantly enhanced the activity of vancomycin but had little effect upon the activity of levofloxacin. For MRSA 494, vancomycin plus rifampin resulted in the greatest killing (P < 0.05). Development of resistance was not detected with any regimen. Levofloxacin may be a useful therapeutic alternative in the treatment of staphylococcal endocarditis, and further study with animal models of endocarditis or clinical trials are warranted.

Anti-Bacterial Agents↗
PubMed1995

De novo nonreciprocal translocation 1;8 confirmed by fluorescent in situ hybridization.

Constitutional nonreciprocal translocations are extremely rare, and even their existence is controversial. We report on a newborn infant with a de novo nonreciprocal translocation between chromosomes 1 and 8 resulting in 1q42.3 deletion syndrome. Fluorescent in situ hybridization with whole chromosome paints confirmed the conventional cytogenetic diagnosis.

Abnormalities, Multiple↗
PubMed1995

Bactericidal killing activities of cefepime, ceftazidime, cefotaxime, and ceftriaxone against Staphylococcus aureus and beta-lactamase-producing strains of Enterobacter aerogenes and Klebsiella pneumoniae in an in vitro infection model.

Cefepime (CP) is a new injectable cephalosporin with a broad spectrum of activity and stability against common chromosomally and plasmid-mediated beta-lactamases. The bactericidal activities of CP, ceftazidime (CZ), cefotaxime (CTX), and ceftriaxone (CAX) against reference and clinical strains of Staphylococcus aureus, an isogenic pair of Enterobacter aerogenes strains (wild type and a CZ-resistant derepressed mutant), and a Klebsiella pneumoniae isolate possessing a TEM-10 beta-lactamase were investigated in a two-compartment pharmacodynamic in vitro infection model which simulates human pharmacokinetics. An inoculum of approximately 10(6) CFU/ml was used in all model experiments. Antibiotics were administered to simulate the following regimens: CP at 2 g every 12 h (q12h), CZ at 2 g q8h, CTX at 2 g q8h, and CAX at 2 g q24h. Human albumin was added during experiments with CAX and staphylococci to simulate protein binding. Samples were removed at multiple time points over a 48-h period to determine the inoculum size for time-kill curves. Development of resistance was detected by inoculating samples obtained at 0, 24, and 48 h onto antibiotic-containing agar plates. The time to 99.9% killing was used to compare drug regimens. Against staphylococci, the time to bacterial eradication was significantly delayed with CAX-albumin. All regimens had similar activities against the wild-type Enterobacter strain; however, regrowth was noted with CZ, CTX, and CAX against the CZ-resistant strain. There were no differences between the CP, CTX, and CAX regimens against K. pneumoniae. Of interest, no regrowth of any organism was noted with CP. These data indicate that CP has activity against S.aureus and CZ-resistant gram-negative bacilli.

Bacterial Infections↗
PubMed1995

Pharmacodynamics of ceftazidime administered as continuous infusion or intermittent bolus alone and in combination with single daily-dose amikacin against Pseudomonas aeruginosa in an in vitro infection model.

We compared the pharmacodynamics and killing activity of ceftazidime, administered by continuous infusion and intermittent bolus, against Pseudomonas aeruginosa ATCC 27853 and ceftazidime-resistant P. aeruginosa 27853CR with and without a single daily dose of amikacin in an in vitro infection model over a 48-h period. Resistance to ceftazidime was selected for by serial passage of P. aeruginosa onto agar containing increasing concentrations of ceftazidime. Human pharmacokinetics and dosages were simulated as follows: half-life, 2 h; intermittent-bolus ceftazidime, 2 g every 8 h (q8h) and q12h; continuous infusion, 2-g loading dose and maintenance infusions of 5, 10, and 20 micrograms/ml; amikacin, 15 mg/kg q24h. There was no significant difference in time to 99.9% killing between any of the monotherapy regimens or between any combination regimen against ceftazidime-susceptible P. aeruginosa. Continuous infusions of 10 and 20 micrograms/ml killed as effectively as an intermittent bolus of 2 g q12h and q8h, respectively. Continuous infusion of 20 micrograms/ml and an intermittent bolus of 2 g q8h were the only regimens which prevented organism regrowth at 48 h, while a continuous infusion of 5 micrograms/ml resulted in the most regrowth. All of the combination regimens exhibited a synergistic response, with rapid killing of ceftazidime-susceptible P. aeruginosa and no regrowth. Against ceftazidime-resistant P. aeruginosa, none of the ceftazidime monotherapy regimens achieved 99.9% killing. The combination regimens exhibited the same rapid killing of the resistant strain as occurred with the susceptible strain; however, regrowth occurred with all regimens. The combination regimens of continuous infusion of 20 micrograms/ml plus amikacin and intermittent bolus q8h or q12h plus amikacin continued to be synergistic. Overall, continuous infusion monotherapy with ceftazidime at concentrations 4 to 5 and 10 to 15 times the MIC was as effective as an intermittent bolus of 2 g q12h (10 to 15 times the MIC) and q8h (25 to 35 times the MIC), respectively, against ceftazidime-susceptible P. aeruginosa. Combination therapy with amikacin plus ceftazidime, either intermittently q8h or by continuous infusion of 20 micrograms/ml, appeared to be effective and exhibited synergism against ceftazidime-resistant P. aeruginosa.

Amikacin↗
PubMed1995

Crosses of NOD mice with the related NON strain. A polygenic model for IDDM.

Chromosome locations of non-major histocompatibility complex (MHC) genes contributing to insulin-dependent diabetes mellitus (IDDM) in mice have been determined by outcrossing NOD mice to other inbred strains congenic for the NOD MHC haplotype (H2g7). At least nine non-MHC IDDM susceptibility genes (Idd) were previously identified at first backcross (BC1) after outcross of NOD to C57BL/10.H2g7 congenic mice (B10.H2g7). We investigated whether the same set of Idd loci segregated with IDDM susceptibility after outcross of NOD to NON.H2g7 congenic mice. Since the outcrosses to NON.H2g7 and B10.H2g7 were performed in the same vivarium, direct comparisons were made of the chromosomal locations and relative strengths of Idd alleles in diabetic progeny from the two different outcrosses. In comparison with the NOD x B10.H2g7 outcross, the NOD x NON.H2g7 outcross produced significantly higher IDDM frequencies in F1, F2, and BC1 generations. The high F2 diabetes frequency allowed evaluation of the effects of homozygous expression of both the susceptibility and the resistance allele at Idd loci. This analysis demonstrated that no single non-MHC Idd locus was essential for the onset of diabetes in this cross. After outcross to NON.H2g7, Idd4 (chromosome [Chr] 11), Idd5 (Chr 1), and Idd8 (Chr 14) did not segregate with IDDM in either the BC1 or the F2 generation. Diabetogenic NOD-derived alleles at Idd2 (Chr 9), Idd3 (Chr 3), and Idd10 (Chr 3) were segregating in the BC1. An NON-derived allele contributing to susceptibility on Chr 7 (Idd7) was also detected. Dominant traits, detectable only in the F2 cross, were encoded by Chr 4 (Idd9) and two newly mapped loci on Chr 13 (Idd14) and 5 (Idd15). A third dominant trait was encoded by Chr 6 (possibly Idd6), but here, in contrast to Idd9, Idd14, and Idd15, the NON allele was diabetogenic. Stepwise logistic regression analysis of the BC1 and F2 data confirmed that the ability to identify certainty of the non-MHC Idd loci was contingent on the extent of homozygosity for NOD background genes. This study shows that the diabetogenic phenotype can be achieved through the actions of variable combinations of MHC-unlinked genes and a diabetogenic MHC haplotype.

Animals↗
PubMed1995

Cobas Integra: clinical laboratory instrument with continuous and random-access capabilities.

The Cobas Integra from Roche Diagnostic Systems is a new clinical laboratory analyzer with continuous and random-access features for routine chemistries, specific proteins, electrolytes, hormones, therapeutic drugs, and drugs of abuse. The system maintains 68 test-specific reagent cassettes on board, along with multiple ion-selective electrodes (ISEs) for electrolyte determinations. This gives the Cobas Integra the capability of analyzing as many as 72 analytes without having to load additional reagents. We describe the basic analyzer configuration and the subsystems for absorbance, fluorescence polarization, and ISE measurements. Performance characteristics for precision, methods comparison, and on-board stability are given for assays representative of the various test groups. The 29 Cobas Integra tests evaluated in the present study show good agreement (r > or = 0.98 and slopes generally 0.90 to 1.12) with the respective methods available on either the Olympus AU5000, Hitachi 911 or 717, Behring BNA, or Abbott TDx systems. Total assay precision (CV) ranged from 0.8% to 8.5%, and calibration curves were stable for as long as 20 weeks. Test throughput, which is dependent on pipetting sequence, was determined to be up to 600 tests per hour without ISE and up to 750 tests per hour with ISE; the time to first result was 2.0-10.0 min.

Calibration↗
PubMed1994

A genome-wide search for human type 1 diabetes susceptibility genes.

We have searched the human genome for genes that predispose to type 1 (insulin-dependent) diabetes mellitus using semi-automated fluorescence-based technology and linkage analysis. In addition to IDDM1 (in the major histocompatibility complex on chromosome 6p21) and IDDM2 (in the insulin gene region on chromosome 11p15), eighteen different chromosome regions showed some positive evidence of linkage to disease. Linkages to chromosomes 11q (IDDM4) and 6q (IDDM5) were confirmed by replication, and chromosome 18 may encode a fifth disease locus. There are probably no genes with large effects aside from IDDM1. Therefore polygenic inheritance is indicated, with a major locus at the major histocompatibility complex.

Adolescent↗
PubMed1994

Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping.

To facilitate large-scale genetic mapping of the human genome, we have developed chromosome-specific sets of microsatellite marker loci suitable for use with a fluorescence-based automated DNA fragment analyser. We present 254 dinucleotide repeat marker loci (80% from the Généthon genetic linkage map) arranged into 39 sets, covering all 22 autosomes and the X chromosome. The average distance between adjacent markers is 13 centiMorgans, and less than 4% of the genome lies more than 20 cM from the nearest marker. Each set of microsatellites consists of up to nine marker loci, with allele size ranges that do not overlap. We selected marker loci on the basis of their reliability in the polymerase chain reaction, polymorphism content, map position and the accuracy with which alleles can be scored automatically by the Genotyper program.

Automation↗
PubMed1993

Polygenic control of autoimmune diabetes in nonobese diabetic mice.

Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to diabetes or the prediabetic lesion, insulitis, indicative of a polygenic mode of inheritance. The relative importance of these loci and their interactions have been assessed using a new application of multiple polychotomous regression methods. A candidate disease gene, interleukin-2 (Il-2), which is closely linked to insulitis and diabetes, is shown to have a different sequence in NOD, including an insertion and a deletion of tandem repeat sequences which encode amino acid repeats in the mature protein.

Amino Acid Sequence↗
PubMed1993

Effect of sex on the induction of anti-DNA antibodies in normal mice immunized with bacterial DNA.

Immunization of normal mice with bacterial DNA elicits a significant IgG anti-DNA response and has been explored as a model of systemic lupus erythematosus. To determine whether this induced response is influenced by sex, we have measured anti-DNA levels in normal male and female BALB/c mice immunized with single stranded DNA from E. coli as complexes with methylated bovine serum albumin (mBSA) in adjuvant. By ELISA assays, anti-DNA levels of immunized females were approximately 16-fold higher than those of immunized males; levels of antibodies to the mBSA carrier were similar, however. The antibodies from females and males showed a similar degree of cross-reactivity when assayed using other natural and synthetic DNA antigens, including mammalian DNA. These findings suggest the potentiation of anti-DNA production in females by antigen-specific mechanisms and provide further evidence that immunization with bacterial DNA replicates features of autoantibody production in SLE.

Animals↗