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1.  Mathematical model for describing cerebral oxygen desaturation in patients undergoing deep hypothermic circulatory arrest 
Surgical treatment for aortic arch disease requiring periods of circulatory arrest is associated with a spectrum of neurological sequelae. Cerebral oximetry can non-invasively monitor patients for cerebral ischaemia even during periods of circulatory arrest. We hypothesized that cerebral desaturation during circulatory arrest could be described by a mathematical relationship that is time-dependent.
Cerebral desaturation curves obtained from 36 patients undergoing aortic surgery with deep hypothermic circulatory arrest (DHCA) were used to create a non-linear mixed model. The model assumes that the rate of oxygen decline is greatest at the beginning before steadily transitioning to a constant. Leave-one-out cross-validation and jackknife methods were used to evaluate the validity of the predictive model.
The average rate of cerebral desaturation during DHCA can be described as: Scto2[t]=81.4−(11.53+0.37×t) (1−0.88×exp (−0.17×t)). Higher starting Scto2 values and taller patient height were also associated with a greater decline rate of Scto2. Additionally, a predictive model was derived after the functional form of a×log (b+c×δ), where δ is the degree of Scto2 decline after 15 min of DHCA. The model enables the estimation of a maximal acceptable arrest time before reaching an ischaemic threshold. Validation tests showed that, for the majority, the prediction error is no more than ±3 min.
We were able to create two mathematical models, which can accurately describe the rate of cerebral desaturation during circulatory arrest at 12–15°C as a function of time and predict the length of arrest time until a threshold value is reached.
PMCID: PMC2791548  PMID: 19933513
brain, ischaemia; brain, oxygen consumption; hypothermia
2.  Cerebral oximetry in cardiac and major vascular surgery 
We describe the development and current applications of cerebral oximetry (based on near-infrared reflectance spectroscopy) that can be used during cardiac and major vascular surgery to determined brain tissue oxygen saturation. There are presently three cerebral oximetry devices with FDA approval in the United States to measure and monitor cerebral tissue oxygen saturation. 1. INVOS (Somanetics Corporation, Troy, MI - recently COVIDIEN, Boulder, CO); FORE-SIGHT (CAS Medical Systems, Inc. Branford, CT); EQUANOX (Nonin Medical Inc.Minnesota, MN). All devices are portable, non-invasive and easy to use in operating room and intensive care unit. The data provided in these communication may provided information for improvement of perioperative neuromonitoring techniques, and may be crucial in the design of future clinical trials.
PMCID: PMC3484590  PMID: 23439275
cerebral oximetry; detection of cerebral hypoperfusion or ischemia
3.  Immunochemical cross-reactions between type III group B Streptococcus and type 14 Streptococcus pneumoniae. 
Infection and Immunity  1979;25(3):960-963.
Serological cross-reactions between certain streptococci and some serotypes of Streptococcus pneumoniae have been reported. These studies detail the serological cross-reactivity observed between hot HCl-extracted group b streptococcus type III (GBS III) antigens and S. pneumoniae type 14 (Pn 14) polysaccharide. Similar electrophoretic migration patterns of GBS III and Pn 14 were observed when either type-specific BGS III antisera or pneumococcal omniserum was utilized to precipitate these antigens. Both the GBS III antigen and the Pn 14 polysaccharide migrated toward the cathode, whereas all other pneumococcal polysaccharides migrated toward the anode. No cross-reactions were observed between GBS III antisera and the 11 other types of pneumococcal polysaccharides. Lines of identity were observed between type-specific GBS III antisera and monospecific Pn 14 antiserum with either GBS III antigens or purified Pn 14 polysaccharide. The cross-reacting antigens of GBS III and Pn 14 appear to be identical by immunodiffusion and immunoelectrophoresis.
PMCID: PMC414541  PMID: 40876
4.  Improved detection of bacterial antigens by latex agglutination after rapid extraction from body fluids. 
Journal of Clinical Microbiology  1984;20(5):981-984.
Nonspecific agglutination of antibody-coated latex particles, unrelated to the presence of specific bacterial antigens, is a major difficulty with commercial latex particle agglutination tests. Rheumatoid and other factors are known to interfere with latex tests. We studied the use of six chelating, reducing, and anticoagulatory reagents in a rapid extraction of antigen procedure to free heat-stable antigens of Haemophilus influenzae type b and group B streptococcus which had been added to human sera. We also screened sera for the incidence of nonspecific agglutination from the three following groups: 123 patients with positive serology tests, 112 hospitalized patients, and 87 blood donors. The rapid extraction of antigen procedure involved a 1:4 dilution of the sera with each of the six reagents, incubation at 100 degrees C for 3 min, and centrifugation at 13,000 X g for 5 min. Two commercial latex kits were tested (Bactigen and Wellcogen). Nonspecific agglutination was entirely eliminated by each of the six extraction reagents. Sera from 52% of the patients with positive serology tests, 29% of the hospitalized patients, and 28% of the blood donors showed nonspecific agglutination with Bactigen before extraction. Nonspecific agglutination was eliminated in all but one sample after the rapid extraction of antigen procedure. This simple, rapid extraction procedure eliminated nonspecific reactions in cerebrospinal fluids and amniotic fluids and reduced this problem in urines and sera with each commercial kit used on clinical specimens.
PMCID: PMC271488  PMID: 6439735
5.  Detection of group B streptococcal antigens in amniotic fluid of rhesus monkeys. 
Journal of Clinical Microbiology  1983;17(6):1127-1131.
To simulate group B streptococci (GBS) amniotic fluid infections common in humans and to examine bacterial growth and the appearance of GBS antigens in vivo, GBS were injected into the amniotic cavity of 19 near-term rhesus monkeys. Transabdominal aspirates of amniotic fluid were obtained before bacterial challenge, after 2 and 6 h, and during cesarean section delivery (24 h). Each fluid was quantitatively cultured for GBS. Specimens of amniotic fluid and gastric aspirate from each infant were tested for the presence of GBS antigens with a commercial latex particle agglutination test (Wellcogen Strep B; Wellcome Diagnostics, Dartford, England). To eliminate nonspecific latex particle agglutination reactivity, presumably caused by proteins, a processing procedure was required. Despite active proliferation of bacteria, only 12% of the 2-h amniotic specimens were latex particle agglutination positive. In contrast, 94% of th3 6-h and 100% of the 24-h specimens had detectable antigens, as did 89% of the gastric fluid specimens aspirated from the 19 newborns. Latex particle agglutination tests, after proper processing, will readily detect GBS antigens in amniotic or gastric aspirate fluid from experimentally infected rhesus monkeys.
PMCID: PMC272813  PMID: 6348078
6.  Evaluation of Miconazole Therapy in Experimental Disseminated Candidiasis in Laboratory Rats 
Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 × 106Candida albicans was intravenously injected into 250- to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in Candida-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed C. albicans and a marked inflammatory response in the kidney, brain, and heart. C. albicans organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group. Miconazole appears to be an efficacious drug for parenteral therapy, as demonstrated in this reproducible model of disseminated candidiasis in laboratory rats, and more extensive experimental studies are indicated.
PMCID: PMC352234  PMID: 646350
8.  Characterization of multi-drug resistant Mycobacterium tuberculosis from immigrants residing in the USA using Ion Torrent full-gene sequencing 
Epidemiology and Infection  2013;142(6):1328-1333.
Drug-resistant Mycobacterium tuberculosis bacterium (MTB) is spreading worldwide. Three drug-resistant isolates were detected in Burmese, Hmong, and Indian immigrants currently residing in Milwaukee, Wisconsin, USA. Ion Torrent full-gene sequencing and complete genetic analysis was performed within 5 days and compared to results from traditional drug sensitivity testing (DST). Genetic characterization of seven, full-length resistance-associated genes revealed two MDR and one highly resistant strain with important drug-resistant mutations that were confirmed by traditional DST. The rapid turnaround from sample-to-sequence underscores the public health value of Ion Torrent full-gene sequencing of MDR/XDR genes from epidemiologically significant clinical isolates.
PMCID: PMC4045166  PMID: 24073633
Drug resistance genes; Ion Torrent sequencing; MDR; Mycobacterium tuberculosis; next-generation sequencing
9.  Comparison of commercially available group B streptococcal latex agglutination assays. 
Journal of Clinical Microbiology  1991;29(12):2895-2896.
Detection of group B streptococcus (GBS) antigen in urine by latex particle agglutination (LPA) may facilitate the rapid diagnosis of GBS sepsis. We sought to compare three commercial LPA assays with specimens that were spiked with type-specific antigen, group-specific antigen, or type III organisms. There were sensitivity differences between the assays, but the Bactigen assay performed best, detecting as little as 1 ng of GBS group-specific antigen per ml in urine and as few as 10(5) CFU of GBS type III organisms per ml in urine, serum, and cerebrospinal fluid.
PMCID: PMC270458  PMID: 1757570
10.  Rapid detection of group B streptococcal antigen in human amniotic fluid. 
Journal of Clinical Microbiology  1987;25(2):259-262.
Infants exposed in utero to group B streptococcus (GBS)-infected human amniotic fluid (HAF) are at high risk for serious infection. Latex particle agglutination (LPA) tests are not approved for detection of GBS in HAF. Two LPA systems, Patho-Dx Strep B and Wellcogen Strep B, were used to test unfiltered sterile HAF and filtered HAF containing concentrations of GBS carbohydrate from 0.2 to 100 micrograms/ml. Four different processing techniques were used to prevent nonspecific LPA: EDTA, nitrous acid, enzyme, and nitrous acid-heat. GBS (10(2) CFU/ml) was inoculated into filtered HAF, incubated, sampled serially, processed with enzyme, and tested by LPA. Unprocessed, unfiltered HAF showed 33% nonspecific agglutination when tested by LPA. Processing of HAF removed nonspecific agglutination and improved GBS antigen detection. Without processing, LPA could not detect less than 100 micrograms of GBS carbohydrate per ml. With nitrous acid or enzyme processing, as little as 0.2 microgram/ml could be detected. Results were easier to read after enzyme processing than after nitrous acid processing. Although both LPA systems were equally efficient, testing was easier with the Patho-Dx system. After enzyme processing, LPA could detect as few as 10(4) CFU/ml when agglutination was read with a 4 X hand lens. Substances in HAF induce false-positive reactions during LPA testing. Processing removes the interference and improves the detection of GBS. LPA testing of HAF may allow earlier identification and treatment of infants at risk for serious GBS infection.
PMCID: PMC265879  PMID: 3546363

Results 1-10 (10)