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C F Babbs

Publications and source records attributed to C F Babbs.

At least 19 recordsLinked to original sources
PubMed1992

A computer-based, automated, telephonic system to monitor patient progress in the home setting.

In this report we describe an automated, telephonic system to monitor the progress of patients convalescing at home. The system includes a computerized central station that is capable of automated voice communication over the telephone, using voice reproduction, and touch-tone recognition. Peripheral hardware in multiple monitored homes need include only a touch-tone telephone, but may also be augmented by inexpensive, rudimentary diagnostic aids, such as a scale for body weight, a thermometer, or a blood pressure cuff and manometer. Current central hardware includes a NeXT computer, a fax modem, and a specialized telecommunications modem developed specifically for voice telecommunication using the NeXT. The central station acts like a robotic nurse in that it asks patients a series of questions and records the responses. The subjective questions to be asked are patient individualized and pre-selected by the physician from a question menu including items targeted specifically for the patient's disease or condition. In addition, clinical data such as body weight, blood pressure, and body temperature obtained from in-home diagnostic aids may be transmitted to the central station over the telephone using touch tones. The time-of-day and frequency of calling are pre-selectable, according to the patient's preference and clinical status. Data obtained by the central station can be easily accessed by the duty nurse via menu driven software. Reports depicting significant responses as a function of time are generated in graphical format to facilitate rapid identification of adverse trends. Hard copy reports can be dispersed directly by fax. Results from a pilot study show patients with cardiac disease readily use the system without difficulty or complaints. In one patient a five pound increase in body weight was detected, which prompted the patient's cardiologist to adjust his medication. In this way automated telephone follow-up can provide early detection of complications before they become severe, making the home environment safer and more secure for convalescence and contributing to reduced health-care costs.

Computer Systems↗
PubMed1992

Droop: a rapidly computable descriptor of local minimum tissue temperature during conductive interstitial hyperthermia.

Although the goal of local hyperthermia therapy for cancer is to elevate the temperature of a tumour to cytotoxic levels, without the presence of 'cold spots', varying blood flow has made the achievement of consistent, therapeutic temperature distributions extraordinarily difficult. The paper presents a novel approach to estimating local minimum tumour temperatures during conductive interstitial hyperthermia which facilitates identification and elimination of cold spots. Conductive interstitial hyperthermia is modelled mathematically for a parallel array of implanted, electrically heated catheters which warms the treated tissue by thermal conduction and blood perfusion. Computer simulations employing the bioheat transfer equation reveal a predictive relationship between implanted catheter temperature, catheter power, implantation geometry and local minimum tumour temperature. Formulation of this relationship in terms of a parameter named 'droop' allows estimation of local minimum intratumoural temperatures from individual catheter temperature and power. Computer simulations are also performed to determine the sensitivity of the droop-based estimator to variations in properties of the tissue and catheters. Generally, variations in geometry or thermal properties of about 10 per cent cause estimation errors of less than 1 degree C in magnitude. These results suggest that online estimates of thermal 'droop' may provide a practical route to more consistent control of intratumoural minimum temperature during conductive interstitial heat therapy.

Algorithms↗
PubMed1992

Oxygen radicals in ulcerative colitis.

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: (1) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.

Antioxidants↗
PubMed1992

Histochemical demonstration of endothelial superoxide and hydrogen peroxide generation in ischaemic and reoxygenated rat tissues.

OBJECTIVE: The aims were to test and evaluate two novel and independent histochemical methods for detecting the initial postischaemic burst of superoxide and hydrogen peroxide in buffer perfused rat tissues during reflow after 60 min warm ischaemia. METHODS: The first is a high manganese/diaminobenzidine technique, in which superoxide oxidises Mn2+ to Mn3+, which in turn oxidises diaminobenzidine to form amber coloured polymers, observable by light microscopy. The second is a high iron/diaminobenzidine technique, in which hydrogen peroxide oxidises diethylenetriaminepenta-acetate chelated Fe2+ to form intermediate species, which in turn oxidise diaminobenzidine similarly to Mn3+. Various isolated organs of the rat were rendered ischaemic for 60 min, and reperfused with oxygen or air equilibrated buffers containing diaminobenzidine and either Mn2+ or Fe2+. Tissues were fixed by perfusion with Trump's solution and processed for light microscopy. RESULTS: Both manganese and iron methods consistently showed the appearance of reaction product on the luminal surfaces of arterial, capillary, and venular endothelial cells in lung, heart, and intestine of the rat during the first 2 to 3 min of reoxygenation after ischaemia. The histochemical reactions were nearly absent in non-manganese-treated and non-iron-treated controls. Superoxide dismutase strongly inhibited Mn2+/diaminobenzidine reaction product formation and catalase strongly inhibited Fe2+/diaminobenzidine reaction product formation, when tested in specially perfused lung preparations in which these specific antioxidant enzymes were concentrated. CONCLUSIONS: These histochemical techniques provide direct, visual evidence that a burst of reactive oxygen species is generated in postischaemic rat tissues. The Mn2+/diaminobenzidine and Fe2+/diaminobenzidine techniques permit investigation of the endothelium derived reactive oxygen by simple laboratory procedures available to almost any investigator at low marginal cost. The endothelial oxidants so revealed may be of pathophysiological significance in a variety of cardiovascular disorders.

Abdomen↗
PubMed1992

Potential use of simple manganese salts as antioxidant drugs in horses.

The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 microM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 mumoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% saline solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Methylene blue as an inhibitor of superoxide generation by xanthine oxidase. A potential new drug for the attenuation of ischemia/reperfusion injury.

Tissue oxidases, especially xanthine oxidase, have been proposed as primary sources of toxic oxygen radicals in many experimental models of disease states. Among these, ischemia-reperfusion injury may be of the greatest clinical interest. In this paper we propose the use of methylene blue as a means of suppressing the production of superoxide radicals O2- by acting as an alternative electron acceptor for xanthine oxidase. Previous work has indicated that methylene blue accepts electrons from xanthine oxidase at the iron-sulfur center. Initial experiments in our laboratory demonstrated that (1) pairs of electrons from each enzymatic oxidation are transferred to methylene blue, (2) the reduction of methylene blue can be achieved by model iron-sulfur centers, similar to the iron-sulfur center of xanthine oxidase, (3) reduced methylene blue auto-oxidizes to produce H2O2 directly, rather than O2-, and (4) methylene blue is effective at non-toxic levels (2-5 mg/kg) in preventing free radical damage to liver and kidney tissues in an in vitro model of ischemia and reoxygenation. Accordingly, we propose that methylene blue may represent a new class of antioxidant drugs that competitively inhibit reduction of molecular oxygen to superoxide by acting as alternative electron acceptors for tissue oxidases. We have termed these agents "parasitic" electron acceptors.

Animals↗
PubMed1991

Computer-aided design and evaluation of novel catheters for conductive interstitial hyperthermia.

Conductive interstitial heating is a modality in which heating elements are implanted directly into the treated tissue. One implementation of such therapy employs electrically heated catheters that are implanted in staggered, parallel rows. To explore strategies for maximising the uniformity of tissue temperature distributions achieved with heated catheters, a two-dimensional computer model with cylindrical co-ordinates was used to evaluate radially and longitudinally the temperature distributions produced by a typical interior catheter surrounded by other similar catheters. Insights from the computer model led to new designs for catheters containing multiple heating elements that produced more uniform thermal distributions, eliminating previous 'cold spots' within the treatment volume located near the ends of the catheter. The new catheter designs also include compartments for the optional placement of radioactive seeds for simultaneous thermoradiotherapy.

Biomedical Engineering↗
PubMed1991

Design and evaluation of closed-loop feedback control of minimum temperatures in human intracranial tumours treated with interstitial hyperthermia.

The dynamic nature of blood flow during hyperthermia therapy has made the control of minimum tumour temperature a difficult task. The paper presents initial studies of a novel approach to closed-loop control of local minimum tissue temperatures utilising a newly developed estimation algorithm for use with conductive interstitial heating systems. The local minimum tumour temperature is explicitly estimated from the power required to maintain each member of an array of electrically heated catheters at a known temperature, in conjunction with a new bioheat equation-based algorithm to predict the 'droop' or fractional decline in tissue temperature between heated catheters. A closed loop controller utilises the estimated minimum temperature near each catheter as a feedback parameter, which reflects variations in local blood flow. In response the controller alters delivered power to each catheter to compensate for changes in blood flow. The validity and stability of this estimation/control scheme were tested in computer simulations and in closed-loop control of nine patient treatments. The average estimation error from patient data analysis of 21 sites at which temperature was independently measured (three per patient) was 0.0 degree C, with a standard deviation of 0.8 degree C. These results suggest that estimation of local minimum temperature and feedback control of power delivery can be employed effectively during conductive interstitial heat therapy of intracranial tumours in man.

Adult↗
PubMed1991

Limitations of open-chest cardiac massage after prolonged, untreated cardiac arrest in dogs.

STUDY OBJECTIVES: Open-chest cardiac massage is an effective method of resuscitation if instituted within 15 minutes of normothermic cardiac arrest that has failed to respond to ongoing closed-chest CPR efforts. The usefulness of invasive forms of CPR after various periods of untreated cardiac arrest is less certain. This study was performed to determine the effectiveness of open-chest resuscitation after prolonged periods of untreated cardiac arrest. SETTING AND DESIGN: Prospective, controlled laboratory investigation using an animal model of cardiac arrest. Open-chest cardiac massage initially was compared to standard closed-chest compression CPR. The efficacy of open-chest CPR then was evaluated after ten and 40 minutes of untreated ventricular fibrillation. TYPE OF PARTICIPANTS: Twenty mongrel dogs (24 +/- 1 kg). MEASUREMENTS AND MAIN RESULTS: After 20 minutes of untreated ventricular fibrillation, open-chest resuscitation was significantly better than closed-chest efforts for the production of coronary perfusion pressure (58 +/- 14 vs 2 +/- 1 mm Hg; P less than .05) and initial resuscitation success (five of five vs one of five; P less than .03). Open-chest cardiac massage was equally effective for initial resuscitation if begun after ten or 20 minutes of untreated ventricular fibrillation (five of five vs five of five), but if untreated ventricular fibrillation continued for 40 minutes prior to instituting open-chest massage, no resuscitation benefit was found (none of five; P less than .005). There were marked differences in 24-hour survival depending on the length of time untreated cardiac arrest continued prior to instituting open-chest resuscitation efforts. After 20 minutes of ventricular fibrillation, initial resuscitation was successful with open-chest massage, but long-term survival was poor. CONCLUSION: Open-chest cardiac massage did not produce long-term survival if untreated cardiac arrest persisted for 20 or more minutes prior to invasive resuscitation efforts.

Animals↗
PubMed1991

Production of Ah receptor ligands in rat fecal suspensions containing tryptophan or indole-3-carbinol.

An assay system was developed to test whether bacteria in the gastrointestinal tract are capable of metabolizing tryptophan to compounds that are able to bind to the aryl hydrocarbon (Ah) receptor. Tryptophan (1 mM) was added to feces diluted 1:1,000 in phosphate-buffered saline and incubated at 37 degrees C overnight. The suspensions were extracted with chloroform to obtain the hydrophobic compounds. To test for the presence of Ah receptor ligands, a competition binding assay using [2-125I]iodo-7, 8-dibromodibenzo-p-dioxin and Hepa 1c1c7 cytosol was employed; it was capable of detecting picogram levels of a competing ligand with similar affinity. Fecal suspensions in the presence of 1 mM tryptophan and oxygen are capable of producing greater than 60% inhibition of radioligand binding per 10 micrograms of feces. In contrast, oxygen-equilibrated fecal suspensions without tryptophan and argon-equilibrated fecal suspensions with tryptophan exhibited 10% inhibition of radioligand binding per 10 micrograms of feces in the competition binding assay. Other indolylic compounds and amino acids were similarly tested. Histidine, tyrosine, phenylalanine, glycine, indole-3-acetic acid, and tryptamine were all negative in this assay. Indole-3-carbinol was capable of forming compounds that bind to the Ah receptor under a variety of conditions: in fecal suspensions with or without oxygen, in 50 mM HCl for 80 minutes, and in neutral pH buffer overnight at 37 degrees C. Addition of oxygenated tryptophan-fecal incubation extracts to Hepa 1 and Hepa c4 mutant (defective Ah receptor) cell cultures resulted in the induction of ethoxyresorufin O-deethylase activity in Hepa 1 cells, but no induction was observed in Hepa c4 cells. These results suggest that bacteria in the gastrointestinal tract under the proper conditions are able to metabolize tryptophan to compounds that are Ah receptor ligands.

Animals↗
PubMed1991

Comparison of canine skeletal muscle power from twitches and tetanic contractions in untrained muscle: a preliminary report.

Power output and blood flow were determined in dogs for four muscles (gastrocnemius, latissimus dorsi, rectus abdominis, and triceps) to determine effects of choice of muscle, tetany or twitch rates, force loading of the muscle, and blood flow on muscle power output. Total power for a 20-Kg dog was greatest for triceps at 0.77 watts (W) and least for rectus at 0.22 W; power per gram was greatest for gastrocnemius at 5.77 mW/g. Muscle perfusion of latissimus and rectus is greatly decreased by overstretching of the muscle. Overstretching also produces severe, persistent, power loss in latissimus and rectus muscles. Gastrocnemius and triceps tolerate stretching much better. We conclude that power can be improved without causing muscle fatigue by choice of muscle, choice of electrical stimulation parameters, linear geometry for contraction of the muscle, and matching the force load to each individual muscle.

Abdominal Muscles↗
PubMed1991

Cytochemical studies of hydrogen peroxide generation in postischemic hepatocytes.

Reoxygenation injury that occurs when blood circulation is restored to previously ischemic tissues is currently discussed as a pathophysiological entity distinct from the primary anoxic injury that develops during ischemia per se. To test the hypothesis that reoxygenation injury in hepatocytes is caused by a postischemic burst of reactive oxygen species (ROS), including superoxide radicals, O2-., and hydrogen peroxide, H2O2, we performed a cytochemical study exploiting the peroxidase activity within peroxisomes as a sensitive ultrastructural detector of intracellular H2O2 generation. The osmiophilic polymer formed when tissue peroxidase is incubated with 3,3'-diaminobenzidine (DAB) and H2O2 was used as a marker for endogenous H2O2 in rat liver slices in short-term organ culture subjected to a cycle of 60-min ischemic anoxia and 30-min reoxygenation in the presence of DAB without exogenous H2O2. Peroxisomal reaction product was quantitatively evaluated in transmission electron micrographs of systematically sampled hepatocytes. Mean densities of positive peroxisomes per 1,000 micron2 (+/- SE) in liver slices subjected to various treatments were as follows: continuous anoxia (negative control) 0 +/- 0; normoxia + exogenous H2O2 (positive control) 45 +/- 12; normoxia only 26 +/- 2; ischemia-reoxygenation 13 +/- 6; ischemia-reoxygenation + xanthine oxidase inhibitor, oxypurinol 5 +/- 3; ischemia-reoxygenation + peroxidase inhibitor, aminotriazole 7 +/- 3. Endogenous H2O2 can be detected in hepatocytes by electron microscopic cytochemistry and may in part derive from xanthine oxidase, but it is not substantially increased in the postischemic state. We conclude that hepatocytes do not exhibit a postischemic burst of reactive oxygen species that could cause reoxygenation injury.

Amitrole↗
PubMed1991

Endothelial superoxide production in buffer perfused rat lungs, demonstrated by a new histochemical technique.

This paper describes a new approach to the histochemical demonstration of superoxide generation by pulmonary vascular endothelial cells using a supravital high manganese/diamine technique, in which nascent superoxide radicals induce formation of amber, osmiophilic polymers of diaminobenzidine (DAB), detectable by light or electron microscopy. Superoxide oxidizes Mn2+ ions to the Mn3+ valence state. In turn trivalent manganese readily initiates formation of the polymerized DAB reaction product. Isolated rat lungs were perfused in situ with bloodless, buffered high manganese/DAB salt solution via the pulmonary artery. The aortic root was ligated to minimize outflow from the left heart, so that perfusate shunted across pulmonary capillary endothelium, to fill the alveolar spaces and drain via the trachea. Lungs were perfused for 3 min with oxygen equilibrated buffer, with or without 60 min prior warm anoxia, induced by initial perfusion with argon sparged buffer. After aldehyde fixation and tissue processing DAB reaction product was detected on the inner, luminal surface of the vascular endothelium by both light and electron microscopy. Bronchi and epithelial cells never stained positively. The histochemical reaction was absent or markedly reduced in non-manganese treated or superoxide dismutase treated lungs, as well as in lungs perfused with calcium free buffer. The histochemical reaction was not prevented by the xanthine oxidase inhibitors allopurinol or methylene blue. The high manganese/diamine technique provides direct visual evidence of a calcium dependent mechanism by which pulmonary vascular endothelial cells can generate superoxide radicals.

Animals↗
PubMed1991

Endothelial superoxide production in the isolated rat heart during early reperfusion after ischemia. A histochemical study.

This paper describes a histochemical study of superoxide generation in buffer-perfused, isolated rat hearts during the first 2 minutes of reperfusion after 60 minutes of warm ischemia. Superoxide radical production was demonstrated by a modification of Karnovsky's manganese/diaminobenzidine technique, in which superoxide oxidizes Mn++ to Mn ions, which in turn oxidize diaminobenzidine to form amber, osmiophilic polymers, observable by light or electron microscopy. Isolated hearts were rendered ischemic, reperfused with oxygen equilibrated buffer containing Mn++ and diaminobenzidine, fixed by perfusion with Trump's solution, and processed for light and electron microscopy. The method consistently demonstrated evidence of superoxide generation near the luminal surfaces of arterial, capillary, and venular endothelial cells during the first 2 minutes of reoxygenation after ischemia. The histochemical reaction was absent or markedly reduced in non-manganese-treated or nonischemic hearts, as well as in hearts perfused with calcium-free or oxygen-free buffers. The histochemical differences were statistically significant on quantitative morphometric analysis. These results provide direct, visual evidence of the existence and endothelial localization of a burst of superoxide radicals in intact, postischemic myocardium and suggest the pathophysiologic importance of calcium-dependent endothelial cell activation in the initiation of reperfusion injury.

3,3'-Diaminobenzidine↗
PubMed1990

Quantitation of the hydroxyl radical by reaction with dimethyl sulfoxide.

This investigation was conducted to validate the use of dimethyl sulfoxide (DMSO) as a quantitative molecular probe for the generation of hydroxyl radicals (HO.) in aqueous systems. Reaction of HO. with DMSO produces methane sulfinic acid as a primary product, which can be detected by a simple colorimetric assay. To evaluate this method for estimating total HO. production, we studied three model systems, including the Fenton reaction, gamma irradiation of water, and ultraviolet photolysis of hydrogen peroxide, for which the theoretical maximum yield of HO. could be calculated and compared to measured DMSO oxidation. The results confirm that 0.05 to 1 M DMSO may be used to capture nearly all of the expected HO. radicals formed. Thus, methane sulfinic acid production from DMSO holds promise as an easily measured marker for HO. formation in aqueous systems pretreated with DMSO.

Chemical Phenomena↗