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H Warner

Publications and source records attributed to H Warner.

At least 19 recordsLinked to original sources

Ion-exchange column chromatographic method for assaying purine metabolic pathway enzymes.

High energy phosphate levels fall rapidly during cardiac ischemia and recover slowly (more than one week) during reperfusion. The slow recovery of ATP may reflect a lack of purine metabolic precursors and/or increased activity of purine catabolic enzymes such as 5'-nucleotidase (5'-NT, EC 3.1.3.5) and adenosine deaminase (ADA, EC 3.5.4.4). The activity of enzymes involved in both the catabolism of ATP precursors (5-NT and ADA) and the restoration of ATP from slow synthetic pathways [adenosine kinase (AK, EC 2.7.1.20), adenine phosphoribosyl transferase (APRT, EC 2.4.2.7) and hypoxanthine phosphoribosyl transferase (HPRT, EC 2.4.2.8)] may directly affect the rate of ATP recovery. Strategies to enhance recovery will depend on the relative activity of these enzymes following ischemia. Their activity in different species and their response to ischemia are not well characterized. Hence, rapid assay methods for these enzymes would facilitate detailed time course studies of their activities in postischemic myocardium. We modified a single ion-exchange column chromatographic method using DEAE-Sephadex to determine the products of incubation of 5'-NT, AK, APRT and HPRT with their respective substrates. The uniformity of the final product measurement procedure for all assays permits the activities of the four enzymes to be rapidly determined in a single tissue sample and facilitates the study of a large number of samples. This technique should also be useful for enzymes of the pyrimidine metabolic pathway.

5'-Nucleotidase

New computer-based tools for empiric antibiotic decision support.

Since 1995 we have been developing a decision-support model, called Q-ID, which uses a series of infectious disease knowledge bases to make recommendations for empirical treatment or to check the appropriateness of current antibiotic therapy. From disease manifestations and risk factors, a differential diagnosis for the patient is generated by a diagnostic medical expert system. The resulting probability of each: disease is multiplied by the expected benefit in improved mortality and morbidity from optimal antibiotic treatment of each disease. To generate empirical treatment recommendations, site-specific data on sensitivity to antibiotics of each organism is used as an estimate of the likelihood of achieving maximum benefit for each disease on the patient's differential. Combining this data with drug and patient specific factors, the model recommends the antibiotic(s) most likely to produce the optimal benefit in this patient with the least risk and expense. In this paper the model is described, excerpts from each of the knowledge bases are presented, and performance of the model in a real case is shown for illustration.

Aged

An interactive patient information and education system (Medical HouseCall) based on a physician expert system (Iliad).

Informed patients are better equipped to participate in their own health care decisions. We present Medical HouseCall (TM), a consumer expert system and medical information guide, derived in part from a diagnostic and treatment software used by physicians (Iliad). HouseCall(TM) generates a differential diagnosis based on the user symptoms and medical history. HouseCall(TM) also provides alerts for potentially harmful drug interactions, allows for the recording of personal medical history, and offers extensive but easy-to-read information about a variety of medical topics. Focus group evaluations of HouseCall (TM) have demonstrated the program's ease of use, as well as an appreciation of technology that can be used at home to investigate and understand health issues and participate in solving medical problems.

Attitude to Computers

Can health/medical informatics be regarded as a separate discipline?

The participants of the panel on education and training in Medical Informatics, concurred that health/medical informatics is today thriving as a separate discipline, despite inevitable uncertainties regarding the future. Conferees discussed the distinctions between physician-built systems and those designed by medical informaticians, focusing on methodology as critical to medical informatics.

Medical Informatics

Implementation of practice guidelines in a clinical setting using a computerized knowledge base (Iliad).

We present the implementation of the indications for surgery for three surgical operations--cholecystectomy, cataract extraction, and knee arthroscopy--in a medical expert system, called Iliad. This implementation operates in the preauthorization service of IHC Health Plans (an insurance company in Salt Lake City) as a basis for reimbursement of services. Patient data collection forms, derived from Iliad knowledge base, were used by 13 participating surgeons to document the objective patient observations that justify the surgery and, then were faxed to IHC where a trained nurse input the data in Iliad. Iliad's decisions and reports on any deviations from guidelines are communicated back to the care provider. The study evaluates the impact of the computerized implementation on process, as measured by a questionnaire, and on outcome as measured by rate of approvals, documentation level, rate of requests, and average cost. The prospective implementation of the computerized guidelines has performed reliably, has been perceived as a preferred alternative to the old preauthorization system, and, most importantly, has enhanced significantly the level of documentation permitting evaluation and determination of appropriateness before surgery.

Arthroscopy

Estimating frequency of disease findings from combined hospital databases: a UMLS project.

Merging data from the Salt Lake VA hospital database and the LDS hospital HELP system into a UMLS sponsored unified patient database has demonstrated that distribution of variables within a disease is hospital independent. Although disease prevalence is clearly not the same among hospitals, analysis of data within a disease group across hospitals can be done using such a merged database. This unified patient database would allow study of unusual diseases not possible using data from a single institution.

Databases, Factual

Iliad training effects: a cognitive model and empirical findings.

Iliad is a diagnostic expert system consisting of an "inference engine" (collection of rules and procedures for making decisions) and a "knowledge base" (collection of medical facts). Iliad's internal medicine knowledge base recognizes 5000 medical findings and covers 1150 diagnostic conditions in 10 subspecialty fields. We used Iliad's simulator mode to train diagnostic skills in junior-year medical students. The results corroborate previous findings documenting Iliad's teaching efficacy. Recent developments in cognitive psychology provide a framework for explaining Iliad's training effects.

Clinical Clerkship

Electroejaculation in spinal cord injury patients: simplified new equipment and technique.

A new simplified electrostimulation system for rectal probe electroejaculation has been developed and tested 17 times in 13 patients. Seminal emissions were obtained easily from 13 of 17 studies and partial emissions were obtained in 4. Patients with cauda equina and conus lesions with partial intact sensorium also could achieve successful ejaculation by longer stimulation from 2 to 5 minutes with lower currents that could be maintained easily and were tolerated by the patient--a feature unique to our new computerized equipment. The simplicity of operation reduces the number of trained personnel for an electrostimulation procedure, which can be done even in an outpatient setting.

Adult

AI solutions.

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Artificial Intelligence

Electrostimulation of erection and ejaculation and collection of semen in spinal cord injured humans.

An electrostimulation system developed for early research with humans and the great apes, and a new constant-current stimulator specifically developed for human use, have been employed in studies with paraplegic men to produce erection and semen release by rectal probe electrostimulation (RPE). Catheter techniques for antegrade collection of the semen, uncontaminated by urine, have also been applied with moderate success. Details of the electronic instrumentation and catheter techniques are given. The procedure used with the patients and electrostimulation and semen collection results are presented.

Ejaculation

Reproductive biology of paraplegics: results of semen collection, testicular biopsy and serum hormone evaluation.

The fertility and urological status of 30 male paraplegics between 20 and 47 years old with lesions between the T2 and L3 levels were examined by studying serum hormone levels (estradiol-17 beta, testosterone, prolactin, and follicle-stimulating and luteinizing hormones), sperm and semen characteristics via testicular biopsy and rectal probe electrostimulation, and urodynamic evaluation. Of the patients 13 had reflexic, 4 hyperreflexic and 13 areflexic bladders. Nine of the 13 patients with reflexic and all 4 with hyperreflexic bladders had a positive external sphincter electromyogram with detrusor-sphincter dyssynergia. When catheters were not used to collect semen during rectal probe electrostimulation, retrograde semen flow into the bladder was the rule. A total of 22 patients could tolerate rectal probe electrostimulation, while 6 who could not were injured at the T12 level or lower. Seminal emissions were obtained from 35 to 42 studies in these 22 patients. Total sperm count was variable; in 22 studies it was greater than 20 million. Progressive motility usually was low; 77 per cent of the patients had less than 20 per cent motility. Of 13 biopsy specimens obtained 6 suggested normal testicular morphology, with tubule atrophy and spermatogenic activity only mildly reduced in 6 of the remaining 7. Serum testosterone and luteinizing hormone values were significantly higher (p less than 0.05) among the paraplegic patients than among intact male volunteers of the same age range. Other serum hormone levels were unchanged. Outcome of rectal probe electrostimulation and biopsy did not relate to the number of years of patient injury. Thus, the principal deterrent to the use of semen collected by rectal probe electrostimulation from paraplegics for artificial insemination resides in a predominantly low sperm motility. Suggestions for improvement of motility include 1) great care to minimize or prevent urinary tract infections, 2) selection of medications for urinary tract care that do not compromise sperm survival and 3) prevention of sperm stagnation in lower tract storage sites, perhaps by use of periodical rectal probe electrostimulation.

Adult

Partial purification and characterization of a uracil-DNA glycosylase from wheat germ.

A uracil-DNA glycosylase has been purified over 1,000-fold from wheat germ, the first such repair activity isolated from a higher plant. The enzyme has a molecular weight of approximately 27,000 and is resistant to metal ion chelators, but inhibited by high concentrations of either mono or divalent cations. This glycosylase is unable to release uracil from the mononucleotides dUMP and dUTP or from wheat germ RNA. Twelve pyrimidine analogues which closely mimic uracil structurally and the nucleoside uridine were examined for their ability to inhibit glycosylase activity. However, only 5-azauracil and 6-aminouracil inhibited enzymatic release of uracil to the same degree as uracil itself. An inhibitor induced by bacteriophage T5 which inhibits Escherichia coli uracil-DNA glycosylase has been shown not to affect the glycosylase isolated from wheat germ, indicating that these two enzymes differ. The ability of the wheat germ uracil-DNA glycosylase to completely remove available uracil from synthetic DNA substrates in which thymine had been replaced by uracil in varying percentages was also examined and found not to depend on percentage of uracil in the substrates.

DNA Glycosylases

Initiation of erection and semen release by rectal probe electrostimulation (RPE).

Instrumentation and methodology are described for rectal probe electrostimulation (RPE) in human males to elicit erection and allow semen collection. This system virtually eliminates shock hazard; the simultaneous monitoring of current, voltage and impedance ensures reliability and repeatability. It was tested with 8 neurologically intact subjects, and 12 paraplegic patients with lesions between T4 and L2. Platinum electrodes delivered current (density never exceeding 0.37 mA per mm. at the electrode) at frequencies of 60 Hz, 20 Hz, and 0.25 Hz. Erection was elicited repeatably in only 1 of the intact subjects, and no seminal emissions or ejaculations occurred. Discomfort prevented current delivery beyond levels even 50 per cent of those safely acceptable. Six of 10 paraplegic patients (2 others had penile implants) developed erections with 20 Hz; the other 2 frequencies were much less effective. The extent of RPE-induced penile tumescence varied directly with electrode surface area and applied current intensity. Discomfort was minimal. Retrograde seminal emission in 5 of the 12 paraplegics was verified by post-stimulation recovery of sperm via voiding or bladder irrigation via catheter. Although motility was very low, 4 of 8 recovered bladder-urine/seminal fluid specimens indicated sperm counts and morphology consonant with use in artificial insemination. Thus, RPE, if combined with techniques to allow antegrade semen collection, may be a useful technique for spinal cord-injured men who, as part of their sexual rehabilitation, are interested in siring children.

Adult

Effects of glucose on insulin release and on intermediary metabolism of isolated perifused pancreatic islets from fed and fasted rats.

We examined the relationship between glucose-induced insulin release and the intermediary metabolism of islets from fed and fasted rats. Isolated islets were perifused and insulin release measured in the effluent. At various times after switching islets from 2.4 to 8.6 or 14.5 mM glucose or from 2.4 to 14.5 and back to 2.4 mM glucose, islets were quickly frozen, freeze dried, and subsequently analyzed for tissue content of glucose-6-P, fructose-1,6-P2 plus triose-P, Pi, ATP, ADP, 5'-AMP, NADH, NADPH, total NAD, and total NADP using enzymatic fluorometric procedures. When islets from fed rats were exposed to high glucose, there were concomitant increases of insulin release and islet content of glucose-6-P, fructose-1,6-P2 plus triose-P, NADH, and NADPH. During stimulation Pi and 5'-AMP content fell markedly. The total adenine nucleotide content remained constant. Similar secretory and metabolic changes occurred when 1.5 mM Pi was added to the perifusion fluid. When glucose-stimulated islets were switched back to low glucose for 10 min, all substances but fructose-1,6-P2 plus triose-P, 5'-AMP, NADPH, and possibly ATP returned to the prestimulatory level. Starvation of rats for 3 days blocked the secretory response to 8.6 mM glucose. Fructose-1,6-P2 plus triose-P rose but it did not attain the level existing in islets from fed rats. The ratios (ATP)/(5'-AMP) and (ATP)/(Pi)(adp) increased to the values observed in glucose-stimulated islets of fed rats. The metabolic changes in islets from fed rats exposed to high glucose are consistent with an activation of glycolysis occurring concomitantly with stimulated rates of insulin release. This occurs despite the decrease of important activators of glycolysis--Pi and 5'-AMP. The enhanced glycolysis possibly results from P-fructokinase activation by increased fructose-6-P levels. Activation of glycolysis with 8.6 mM glucose was not as pronounced in islets from starved rats. Despite the different secretory response of islets from fet and fasted rats, the changes of phosphorylation state in the islets, in particular, Pi and 5'-AMP levels, were similar.

Adenosine Diphosphate

Myocardial infarct imaging with 99mTc-pyrophosphate and 99mTc-methylene diphosphonate: lack of correlation.

A prospective study of eight patients with recent transmural myocardial infarction was performed using 99mTc-Sn-pyrophosphate and 99mTc-Sn-methylene diphosphonate in each patient. All pyrophosphate scans were strongly positive whereas the diphosphonate scan was strongly positive in only one case. We conclude that 99mTc-Sn-pyrophosphate is preferable to 99mTc-Sn-methylene diphosphonate for myocardial imaging.

Diphosphates