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Biomedical subjects

M Dunning

Publications and source records attributed to M Dunning.

At least 19 recordsLinked to original sources
PubMed2001

Bone marrow augmentation in kidney transplantation: a large animal study.

Specific immunomodulatory strategies are required to eliminate the need for lifelong dependence on debilitating immunosuppressants. One proposed strategy is to simultaneously transplant the kidney and infuse donor-specific bone marrow cells. We prospectively studied the effect of unmodified donor-specific bone marrow infusion (DSBMI) on rejection, infection, graft-versus-host disease (GvHD), and graft survival. We performed 57 kidney transplants in mixed lymphocyte culture (MLC)-reactive, outbred pigs. The groups of recipient pigs differed according to the use of (1) indefinite versus short-term tacrolimus-based immunosuppression, (2) DSBMI, and (3) recipient preconditioning (RPC: whole body irradiation with 400 rads on day 0 and horse anti-pig thymocyte globulin (ATG) on days -2, -1, and 0). In all, we studied eight groups: group 1, nonimmunosuppressed control pigs (n = 8); group 2, nonimmunosuppressed DSBMI pigs (n = 7); group 3, nonimmunosuppressed RPC + DSBMI pigs (n = 5); group 4, tacrolimus (indefinite) pigs (n = 11); group 5, tacrolimus (10 days only) pigs (n = 5); group 6, DSBMI + tacrolimus (indefinite) pigs (n = 8); group 7, DSBMI + tacrolimus (10 days only) pigs (n = 6); and group 8, RPC + DSBMI + tacrolimus (indefinite) pigs (n = 7). DSBMI alone (group 2) or in combination with RPC (group 3) did not prolong graft survival, as compared with nonimmunosuppressed controls (group 1). In groups 1, 2, and 3, all but one pig died from rejection; in group 3 only, 45% of the pigs died from concurrent infection or GvHD, indicating that RPC in combination with DSBMI aggravated the risk of generalized infection and GvHD. Post-transplant immunosuppression--irrespective of indefinite or short-term administration--was required for prolonged graft survival. With indefinite use of immunosuppression, graft survival rates and death rates from rejection were not different for pigs with (group 6) versus without (group 4) DSBMI; however, the death rate from infection was higher in group 6, suggesting that the bone marrow inoculum increased the risk of systemic infection. With short-term use of immunosuppression, graft survival rates were higher and death rates from rejection lower for pigs with (group 7) versus without (group 5) DSBMI. But DSBMI and short-term immunosuppression (group 7) failed to prolong survival beyond that achieved with indefinite immunosuppression (groups 4 and 6). Although the combination of DSBMI and short-term immunosuppression (group 7) reduced the risk of infection, it did not avert severe rejection. The addition of RPC to DSBMI and indefinite immunosup- pression (group 8) significantly decreased graft survival, as compared with groups 4, 6, and 7. It also increased the incidence of death from rejection, GvHD, and infection, or a combination thereof. Unmodified DSBMI did not prolong graft survival after kidney transplantation, nor did it decrease the incidence of rejection. But it aggravated the risk of GvHD and infection. Short-term immunosuppression with DSBMI reduced the incidence of death from infection or GvHD, but it resulted in a higher incidence of death from rejection (as compared with indefinite use of immunosuppression). RPC, combined with DSBMI and indefinite immunosuppression, increased the death rate from rejection, GvHD, infection, or a combination thereof. In this large animal study, the effect of unmodified DSBMI has been disappointing. The search continues for the optimal way to successfully perform bone marrow augmentation in solid organ transplants.

Animals↗
PubMed2001

Physical factors affecting the production of carbon monoxide from anesthetic breakdown.

BACKGROUND: Parameters determining carbon monoxide (CO) concentrations produced by anesthetic breakdown have not been adequately studied in clinical situations. The authors hypothesized that these data will identify modifiable risk factors. METHODS: Carbon monoxide concentrations were measured when partially desiccated barium hydroxide lime was reacted with isoflurane (1.5%) and desflurane (7.5%) in a Draeger Narkomed 2 anesthesia machine with a latex breathing bag substituting for a patient. Additional experiments determined the effects of carbon dioxide (0 or 350 ml/min), fresh gas flow rates (1 or 4 l/min), minute ventilation (6 or 18 l/min), or absorbent quantity (1 or 2 canisters). End-tidal anesthetic concentrations were adjusted according to a monochromatic infrared monitor. RESULTS: Desflurane produced approximately 20 times more CO than isoflurane when completely dried absorbents were used. Peak CO concentrations approached 100,000 ppm with desflurane. Traces of water remaining after a 66-h drying time (one weekend) markedly reduced the generation of CO compared with 2 weeks of drying. Reducing the quantity of desiccated absorbent by 50% reduced the total CO production by 40% in the first hour. Increasing the fresh gas flow rate from 1 to 4 l/min increased CO production by 67% in the first hour but simultaneously decreased average inspiratory concentrations by 53%. Carbon dioxide decreased CO production by 12% in completely desiccated absorbents. CONCLUSION: Anesthetic identity, fresh gas flow rates, absorbent quantity, and water content are the most important factors determining patient exposures. Minute ventilation and carbon dioxide production by the patient are relatively unimportant.

Absorption↗
PubMed1998

Donor-specific portal blood transfusion in intestinal transplantation: a prospective, preclinical large animal study.

BACKGROUND: Unlike in kidney and heart transplantation, the role of pretransplant donor-specific blood transfusion (DST) has not been studied prospectively in a large animal model of bowel transplantation. We investigated the impact of portal versus systemic DST on overall survival, rejection, graft-versus-host disease (GVHD), and infection after total (small and large) bowel transplantation in pigs. METHODS: Mixed lymphocyte culture-reactive, outbred pigs underwent total enterectomy and orthotopic total bowel transplantation with portal vein graft drainage. One unit of donor blood was transfused via the portal or systemic circulation (according to a randomization protocol) before graft implantation was begun. We studied six groups, all of which underwent at least a total bowel transplant: group 1 (n=5) comprised nonimmunosuppressed control pigs with portal DST; group 2 (n=6), nonimmunosuppressed control pigs with systemic DST; group 3 (n=5), cyclosporine (CsA)-treated pigs with portal DST; group 4 (n=5), CsA-treated pigs with systemic DST; group 5 (n=5), tacrolimus-treated pigs with portal DST; and group 6 (n=5), tacrolimus-treated pigs with systemic DST. All immunosuppressed pigs received prednisone (2 mg/kg/day) and either CsA (to maintain levels between 250 and 350 ng/ml) or tacrolimus (to maintain levels between 10 and 30 ng/ml). Stomal biopsies and autopsies were obtained to study the incidence of rejection, GVHD, and infection. RESULTS: Portal DST and tacrolimus-based immunosuppression resulted in the highest survival rates. At 7, 14, and 28 days after transplantation, survival rates in group 5 were 100%, 100%, and 80%; in group 6, 100%, 60%, and 40%; and in group 3, 100%, 0%, and 0%, respectively. Only the combination of portal DST and tacrolimus prevented the occurrence of, and death from, rejection. Death from rejection at 7, 14, and 28 days in group 5 was 0%, 0%, and 0%; in group 6, 0%, 33%, and 67%; and in group 3, 0%, 100%, and 100%, respectively. Of note, if immunosuppression was used, the groups with portal (versus systemic) DST had a higher risk of death from infection but a lower risk of death from GVHD. Simultaneous immunologic events were noted more frequently in groups with systemic (versus portal) DST. Long-term survival was noted only in groups with tacrolimus-based immunosuppression and was more common for those with portal (versus systemic) DST. CONCLUSIONS: Portal DST at the time of total bowel transplantation and posttransplant immunosuppression with tacrolimus prevent rejection and significantly increase graft survival. The combination of portal antigen presentation and tacrolimus needs to be studied in clinical bowel transplantation.

Animals↗
PubMed1998

Use of omental pedicle grafts in the management of non-healing axillary wounds in 10 cats.

A retrospective analysis of the clinical case histories of 10 domestic shorthaired cats that underwent omentalisation, using a vascular pedicle of greater omentum, of chronic non-healing axillary wounds was carried out. Wounds were debrided and closed in a primary fashion following omentalisation. The cats had undergone a modal number of three previous repair attempts over a three- to 18-month period (mean 11 months) before referral. Further dehiscence occurred in eight cases, requiring a modal number of one further attempt at closure of the wound. Other complications included incisional herniation (two cats), serous exudate from the axillary wound (two cats) and paracostal abscessation (one cat). Long-term cure was achieved in seven of the 10 cases, with wounds finally having healed at a mean of 24 days post-omentalisation. Chronic axillary wounds are particularly difficult to treat and there are no reports of consistently successful techniques for their repair. This report suggests that omentalisation of these wounds may be a step towards such a repair procedure.

Animals↗
PubMed1997

Performance of an electrochemical carbon monoxide monitor in the presence of anesthetic gases.

OBJECTIVE: The passage of volatile anesthetic agents through accidentally dried CO2 absorbents in anesthesia circuits can result in the chemical breakdown of anesthetics with production of greater than 10000 ppm carbon monoxide (CO). This study was designed to evaluate a portable CO monitor in the presence of volatile anesthetic agents. METHODS: Two portable CO monitors employing electrochemical sensors were tested to determine the effects of anesthetic agents, gas sample flow rates, and high CO concentrations on their electrochemical sensor. The portable CO monitors were exposed to gas mixtures of 0 to 500 ppm CO in either 70% nitrous oxide, 1 MAC concentrations of contemporary volatile anesthetics, or reacted isoflurane or desflurane (containing CO and CHF3) in oxygen. The CO measurements from the electrochemical sensors were compared to simultaneously obtained samples measured by gas chromatography (GC). Data were analyzed by linear regression. RESULTS: Overall correlation between the portable CO monitors and the GC resulted in an r2 value >0.98 for all anesthetic agents. Sequestered samples produced an exponential decay of measured CO with time, whereas stable measurements were maintained during continuous flow across the sensor. Increasing flow rates resulted in higher CO readings. Exposing the CO sensor to 3000 and 19000 ppm CO resulted in maximum reported concentrations of approximately 1250 ppm, with a prolonged recovery. CONCLUSIONS: Decrease in measured concentration of the sequestered samples suggests destruction of the sample by the sensor, whereas a diffusion limitation is suggested by the dependency of measured value upon flow. Any value over 500 ppm must be assumed to represent dangerous concentrations of CO because of the non-linear response of these monitors at very high CO concentrations. These portable electrochemical CO monitors are adequate to measure CO concentrations up to 500 ppm in the presence of typical clinical concentrations of anesthetics.

Anesthesia, Closed-Circuit↗
PubMed1997

Reduction in the incidence of carbon monoxide exposures in humans undergoing general anesthesia.

BACKGROUND: Carbon monoxide forms via reaction of isoflurane, enflurane, and desflurane with dried CO2 absorbents. The authors hypothesize that interventions by nonphysician support personnel to decrease absorbent drying will decrease the exposure rate of patients to carbon monoxide from anesthetic breakdown. METHODS: In the control group, all anesthetizing personnel were made aware of the factors enabling CO generation from anesthetic breakdown, and prevention techniques were left to the anesthetizing personnel. After data collection was complete, the following interventions were initiated to reduce absorbent drying: Anesthesia technicians and housekeeping personnel were instructed to turn off all anesthesia machines after the last case of the day in each room, and the CO2 absorbent was changed each morning if fresh gas was found flowing. Baralyme was used in all phases of this study. RESULTS: Five cases of intraoperative carbon monoxide exposure occurred among 1,085 (0.46%) first cases in the control group. Postintervention, patient carbon monoxide exposures decreased (P < 0.05), with one exposure among 1,961 (0.051%) first cases in the main operating room. Two exposures among 68 (2.9%) first cases occurred in remote locations (P < 0.001) versus main operating room. Predisposing factors for absorbent drying include the prolonged use of anesthesia machines for monitored anesthesia care, inappropriate drying techniques for expiratory flowmeters, understaffing of support personnel, and anesthesia in remote locations. CONCLUSIONS: These interventions reduced patient exposure to carbon monoxide. Monitoring for carbon monoxide exposures during general anesthesia may be necessary to recognize and end patient exposures that occur despite preventative measures.

Adsorption↗
PubMed1996

Mass spectrometry provides warning of carbon monoxide exposure via trifluoromethane.

BACKGROUND: The chemical breakdown of isoflurane, enflurane, or desflurane in dried carbon dioxide absorbents may produce carbon monoxide. Some mass spectrometers can give false indications of enflurane during anesthetic breakdown. METHODS: During clinical anesthesia with isoflurane or desflurane, the presence of carbon monoxide in respiratory gas was confirmed when enflurane was inappropriately indicated by a clinical mass spectrometer that identified enflurane at mass to charge ratio = 69. In vitro, isoflurane, enflurane, or desflurane in oxygen was passed through dried carbon dioxide absorbents at 35, 45, and 55 degrees C. Gases were analyzed by gas chromatography and by mass spectrometry. RESULTS: Mass spectrometry identified several clinical incidents in which 30-410 ppm carbon monoxide was measured in respiratory gas. Trifluoromethane was produced during in vitro breakdown of isoflurane or desflurane. Although these inappropriately indicated quantities of "enflurane" correlated (r2 > 0.95) to carbon monoxide concentrations under a variety of conditions, this ratio varied with temperature, anesthetic agent, absorbent type, and water content. CONCLUSIONS: Trifluoromethane causes the inappropriate indication of enflurane by mass spectrometry, and indicates isoflurane and desflurane breakdown. Because the ratio of carbon monoxide to trifluoromethane varies with conditions, this technique cannot be used to quantitatively determine the amount of carbon monoxide to which a patient is exposed. If any warning of anesthetic breakdown results from this technique then remedial steps should be taken immediately to stop patient exposure to carbon monoxide. No warning can be provided for the breakdown of enflurane by this technique.

Anesthetics, Inhalation↗