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Biomedical subjects

Bernard M Churchill

Publications and source records attributed to Bernard M Churchill.

11 recordsLinked to original sources

Use of electrochemical DNA biosensors for rapid molecular identification of uropathogens in clinical urine specimens.

We describe the first species-specific detection of bacterial pathogens in human clinical fluid samples using a microfabricated electrochemical sensor array. Each of the 16 sensors in the array consisted of three single-layer gold electrodes-working, reference, and auxiliary. Each of the working electrodes contained one representative from a library of capture probes, each specific for a clinically relevant bacterial urinary pathogen. The library included probes for Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterocococcus spp., and the Klebsiella-Enterobacter group. A bacterial 16S rRNA target derived from single-step bacterial lysis was hybridized both to the biotin-modified capture probe on the sensor surface and to a second, fluorescein-modified detector probe. Detection of the target-probe hybrids was achieved through binding of a horseradish peroxidase (HRP)-conjugated anti-fluorescein antibody to the detector probe. Amperometric measurement of the catalyzed HRP reaction was obtained at a fixed potential of -200 mV between the working and reference electrodes. Species-specific detection of as few as 2,600 uropathogenic bacteria in culture, inoculated urine, and clinical urine samples was achieved within 45 min from the beginning of sample processing. In a feasibility study of this amperometric detection system using blinded clinical urine specimens, the sensor array had 100% sensitivity for direct detection of gram-negative bacteria without nucleic acid purification or amplification. Identification was demonstrated for 98% of gram-negative bacteria for which species-specific probes were available. When combined with a microfluidics-based sample preparation module, the integrated system could serve as a point-of-care device for rapid diagnosis of urinary tract infections.

Biosensing Techniques↗

Automatic generation of repeated patient information for tailoring clinical notes.

Generating clear, readable, and accurate reports can be a time-consuming task for physicians. Clinical notes, which document patient encounters, often contain a certain set of patient information including demographics, medical history, surgical history, examination results or the current medical condition that is propagated from one clinical note to all subsequent clinical notes for the same patient. To this end, we present a system, which automatically generates this patient information for the creation of a new clinical note. We use semantic patterns and an approximate sequence matching algorithm for capturing the discourse role of sentences, which we show to be a useful feature for determining whether the sentence should be repeated. Our system is shown to perform better than a simple baseline metric using precision/recall results. We believe such a system would allow clinical notes to be more complete, timely, and accurate.

Documentation↗

Rapid, species-specific detection of uropathogen 16S rDNA and rRNA at ambient temperature by dot-blot hybridization and an electrochemical sensor array.

Development of rapid molecular approaches for pathogen detection is key to improving treatment of infectious diseases. For this study, the kinetics and temperature-dependence of DNA probe hybridization to uropathogen species-specific sequences were examined. A set of oligonucleotide probes were designed based on variable regions of the 16S gene of the Escherichia coli, Proteus mirabilis, Klebsiella oxytoca, and Pseudomonas aeruginosa. A universal bacterial probe and probes-specific for gram-positive and gram-negative organisms were also included. The oligonucleotide probes discriminated among 16S genes derived from 11 different species of uropathogenic bacteria applied to nylon membranes in a dot-blot format. Significant binding of oligonucleotide probes to target DNA and removal of nonspecific binding by membrane washing could both be achieved rapidly, requiring as little as 10 min. An oligonucleotide probe from the same species-specific region of the E. coli 16S gene was used as a capture probe in a novel electrochemical 16-sensor array based on microfabrication technology. Sequence-specific hybridization of target uropathogen 16S rDNA was detected through horseradish peroxidase acting as an electrochemical transducer via a second, detector probe. The sensor array demonstrated rapid, species-specific hybridization in a time course consistent with the rapid kinetics of the dot-blot hybridization studies. As in the dot-blot hybridization studies, species-specific detection of bacterial nucleic acids using the sensor array approach was demonstrated both at 65 degrees C and at room temperature. These results demonstrate that molecular hybridization approaches can be adapted to rapid, room temperature conditions ideal for an electrochemical sensor array platform.

Bacteria↗

Measurement of bladder compliance can be standardized by a dimensionless number: theoretical perspective.

OBJECTIVES: To: (i) calculate traditional compliance (CTrad) for a normal bladder by DeltaV/DeltaPdet, where DeltaV is the mean volumetric capacity and DeltaPdet is the detrusor pressure rise; (ii) assess its usefulness; (iii) identify the variables that are necessary for correctly assessing bladder compliance; and (iv) using these variables, report a method that, because it includes the effect of patient age, sex and size, correctly assesses compliance for management strategies. METHODS: We obtained the mean volumetric capacity of a normal bladder (V(cap,NL)) and the mean detrusor pressure rise (P(cap,NL)) on filling a normal bladder to its volumetric capacity from our and other published work; (ii) calculated CTrad for a normal bladder; (ii) showed that the variables necessary for assessing compliance correctly are DeltaV, DeltaPdet, V(cap,NL), and P(cap,NL); and (iii) showed that the relationship among these is the dimensionless number, NWahl(-1), calculated as (DeltaV/V(cap,NL))/(DeltaPdet/P(cap,NL)). This value for individuals with a normal bladder was calculated, tabulated and graphed. RESULTS: Because a normal individual's bladder capacity increases with age while the detrusor pressure increase does not, CTrad increases with age and therefore cannot be used for assessing compliance. Published data substantiate our result that CTrad for an individual with a normal bladder varies from 6.3 at 0.5 years old to 90 mL/cmH2O at 18 years old. NWahl(-1) correctly assesses bladder compliance because it is the same for all normal cases; consequently NWahl(-1) is more practical for clinical use. CONCLUSIONS: Bladder compliance is standardized using DeltaV, DeltaPdet, V(cap,NL), and P(cap,NL) to give NWahl(-1), and bladder compliance is usefully reported using this value.

Adolescent↗

Measurement of bladder compliance can be standardized by a dimensionless number: clinical perspective.

OBJECTIVE: To devise a new, practical and more accurate method for measuring bladder compliance, and to show that traditional estimates of compliance are impractical. MATERIALS AND METHODS: Childhood bladder capacity varies greatly with age while detrusor pressure in a normal bladder does not. Consequently, traditional bladder compliance (DeltaV/DeltaP) increases with age, i.e. maturation. Therefore we devised a standard method that includes normal values of pressures and volumes to calculate and report bladder compliance in children, and that also applies to adults. A dimensionless number (NWahl(-1)) was computed for standardizing bladder compliance, comparing the normalized capacity to normalized pressure by the ratio (DeltaV/V(cap,NL))/(DeltaP/P(cap,NL)), where DeltaP is the pressure at bladder capacity, DeltaV the volume at bladder capacity, V(cap,NL) the volume at mean expected bladder capacity and P(cap,NL) the pressure at mean expected bladder capacity. V(cap,NL) is obtained from nomograms of published data. RESULTS: The bladder compliance of patients undergoing urodynamic testing was calculated using NWahl(-1) and the traditional equation (DeltaV/DeltaP). NWahl(-1) provided a more accurate diagnosis and therefore was of more practical use. CONCLUSIONS: Bladder compliance depends on patient age, sex and size; the new estimate used to standardize bladder compliance is based on these factors and is a dimensionless number. This may help when comparing patients and assessing outcomes.

Adolescent↗

Detrusor pressure rise in a normal bladder.

OBJECTIVE: To determine the detrusor pressure rise of a normal bladder (P(cap,NL)) when filled to capacity. PATIENTS AND METHODS: Twenty-four patients with an apparently normal bladder, i.e. with symptoms but whose cystometrogram (CMG) showed no pathology of any kind and a near-normal pressure vs volume plot, were selected from 218 clinical CMGs. A straight line was fitted to the PV plot of these CMGs and then the P(cap,NL) calculated, e.g. by a straight line extending to the point of the normal expected cystometric bladder capacity (V(cap.NL)). Published data relative to P(cap,NL) were evaluated and compared with the values obtained. RESULTS: The mean (range) P(cap,NL) was 6 (4.5-7) cmH2O for patients with apparently normal bladders infused at the maximum physiological diuresis (MPD). This value was substantiated by three other studies of published values. The P(cap,NL) was 6 cmH2O at infusion rates of 10% of glomerular filtration rate (GFR), 10 cmH2O at 20% of GFR and 7-15 cmH2O for 3-10 times the infusion rate of 10% of GFR. CONCLUSION: P(cap,NL) is independent of age, size and sex and, at constant infusion rates of approximately MPD, will be 6. For infusion rates up to 35 mL/min, it is in the range of 6-15 cmH2O.

Compliance↗

Enhanced objective quantitative cystometric analysis of compliance and contractility.

OBJECTIVE: To show, for pressure-time data from cystometrography (CMG), the potential practical clinical application of automatically identified, displayed, analysed and quantified compliance and contractility, as undesirable high-pressure detrusor storage may be caused by inefficient compliance or uninhibited contractions (UNC). MATERIAL AND METHODS: Bladder contractility was measured by UNC and compliance by relaxed-state detrusor pressure (RSDP), i.e. the detrusor (bladder-abdominal) pressure with all UNC removed. Forty-one CMG examinations were used retrospectively to: (i) validate the separation and identification, by comparing the resulting separate graphs (data) of UNC and RSDP with an expanded time scale for raw vesical and rectal data; (ii) show that the separation is correct by examples; and (iii) show the potential practical utility by results for typical cases. RESULTS: Separation into RSDP and UNC was correctly identified and plotted. The examples showed the utility and four types of UNC ('high', contractions of >25 cmH(2)O of long duration; 'medium', >25 cmH(2)O of short duration; 'low', 4-25 cmH(2)O of short duration; and 'frequent', of 2-6 cmH(2)O). CONCLUSIONS: UNCs as small as 2 cmH(2)O can be detected and measured. The explicit enhanced estimate of compliance and contractility will be useful in the follow-up when comparing different patients and studies, and assist in more appropriate diagnosis and treatment. Because the treatment for bladders with poor contractility differs greatly from those with detrusor instability, the ability to reliably and accurately differentiate between these causes is important.

Humans↗

Automatic generation of repeated patient information for tailoring clinical notes.

Dictating clear, readable, and accurate clinical notes can be a time-consuming task for physicians. Clinical notes often contain information concerning the patient's medical history and current medical condition which is propagated from one clinical note to all follow-up clinical notes for the same patient. In this paper, we present a system which, given a clinical note, automatically determines what information should be repeated, and then generates this information for the physician for a new clinical note. We use semantic patterns for capturing the rhetorical category of sentences, which we show to be useful for determining whether the sentence should be repeated. Our system is shown to perform better than a baseline metric based on precision/recall results. Such a system would allow clinical notes to be more complete, timely, and accurate.

Humans↗

Left-colon antegrade continence enema (LACE) procedure for fecal incontinence.

PURPOSE: Antegrade continence enemas (ACE) are an efficacious therapeutic option for patients with fecal incontinence. The authors review their institution's experience with a variation of the Monti-Malone ACE procedure using the left colon as a source of an intestinal conduit and enema reservoir. METHODS: From 2000 to 2002, 18 patients with fecal incontinence or intractable constipation underwent left-colon ACE (LACE) procedure. Concomitant Mitrofanoff appendicovesicostomy was performed in 15 patients and bladder augmentation in 9. The majority of patients had neural tube defects. A segment of left colon was tubularized, tunneled into the muscular wall of the distal colon, and exteriorized through the left upper quadrant or midabdomen. Stomal catherization and enema installation were started one month postoperatively. RESULTS: Fifteen patients (83%) achieved fecal continence, 2 remain incontinent of stool, and 1 experienced stomal closure (mean follow-up was 24 +/- 9 months). Two patients had stomal stenosis that required revision. The mean enema volume in patient's achieving continence was 360 +/- 216 mL, and the mean transit time was 18 +/- 12 minutes. CONCLUSIONS: LACE is an efficacious procedure for fecal incontinence that can be performed safely at the time of major urologic reconstruction. Administration of enemas into the left colon has several physiologic advantages that result in predictable bowel evacuation.

Adolescent↗