Minimal important change in physical function in trauma patients: a study using the short musculoskeletal function assessment.

PURPOSE: The Short Musculoskeletal Function Assessment (SMFA) questionnaire can be used to evaluate physical functioning in patients with traumatic injuries. It is not known what change in score reflects a meaningful change to patients. The aim was to determine minimal important change (MIC) values of the subscales (0-100) of the Dutch SMFA-NL in a sample of patients with a broad range of injuries. METHODS: Patients between 18 and 65 years of age completed the SMFA-NL and the Global Rating of Effect (GRE) questions at 6-week and 12-month post-injury. Anchor-based MIC values were calculated using univariable logistic regression analyses. RESULTS: A total of 225 patients were included (response rate 67%). The MIC value of the Upper Extremity Dysfunction (UED) subscale was 8 points, with a misclassification rate of 43%. The Lower Extremity Dysfunction subscale MIC value was 14 points, with a misclassification rate of 29%. The MIC value of the Problems with Daily Activities subscale was 25 points, with a misclassification rate of 33%. The MIC value of the Mental and Emotional Problems (MEP) subscale was 7 points, with a misclassification rate 37%. CONCLUSION: MIC values of the SMFA-NL were determined. The MIC values aid interpreting whether a change in physical functioning can be considered clinically important. Due to the considerable rates of misclassification, the MIC values of the UED and MEP subscales should be used with caution.

Long-term physical functioning and quality of life after pelvic ring injuries.

BACKGROUND: Pelvic ring injuries are serious injuries, often associated with substantial morbidity and mortality rates. The long-term consequences of these injuries might affect the patients' personal life. Our aim was to assess the long-term effects of pelvic ring injuries on physical functioning and quality of life (QoL) using validated patient-reported outcome measures (PROMs) and comparing these results to normative data from the general population. PATIENTS AND METHODS: A retrospective cohort study was conducted on adults treated for pelvic ring injuries between 2007 and 2016. Demographics, fracture type, injury mechanism, treatment and complications were recorded. PROMs questionnaires concerning physical functioning (SMFA) and quality of life (EQ-5D) were used. Patients were divided according to their age (18-30, 31-64, 65 and older) and fracture type (Tile/AO type A, B or C). Differences in SMFA and EQ-5D scores of the operatively and non-operatively treated patients and between the study population and general population were analyzed. RESULTS: A total of 413 patients were identified of which 279 were eligible for follow-up. One-hundred and ninety-two (69%) patients responded with a mean follow-up of 4.4 years. Patients reported a median score of 13.9 on the SMFA function index, 16.7 on the bother index, 12.5 on the lower extremity, 18.8 on the activities of daily living and 23.4 on the emotion subscale. A median EQ-5D score of 0.8 was reported. There was no difference in physical functioning and QoL between operatively and non-operatively treated patients. Comparison of these results to normative data of the general population revealed a significant (P < 0.05) decrease in physical functioning and QoL in patients with all types of pelvic ring injuries. CONCLUSION: Long-term physical functioning and QoL in patients who had sustained a pelvic ring injury seems fair, although significantly decreased in comparison with their peers from the general population.

The effect of a preoperative warm-up with a custom-made Nintendo video game on the performance of laparoscopic surgeons.

BACKGROUND: It has previously been shown that short, pre-operative practice with a simulator, box trainer, or certain video games can temporarily improve one's basic laparoscopic skills; the so-called warm-up effect. In this experiment, we tested the hypothesis that Underground video game made for training basic laparoscopic skills, can also be used for a pre-operative warm-up. MATERIALS AND METHODS: 29 laparoscopic experts were randomized into two different groups, which were tested on two different days. Group 1 (n = 16) did a laparoscopic skill baseline measurement using the FLS peg transfer test and the Top Gun cobra rope drill on day 1, and did the same tests on day 2 after a 15 min session with the Underground game. Group 2 (n = 13) did the same, but started with the video game, followed by baseline measurement on day 2. This way, each participant served as its own control. Video recordings of both tasks were later analyzed by two blinded reviewers. RESULTS: On day 1, group 2 was 14.33 % (P = 0.037) faster in completing the peg transfer test. A trend toward better cobra rope scores is also seen. When comparing the average improvement between both days, group 1--which used the game as a warm-up on day 2--showed a 19.61 % improvement in cobra rope score, compared to a 0.77 % score decrease in group 2 (P = 0.002). CONCLUSIONS: This study shows that the Underground video game can be used as a pre-operative warm-up in an experimental setting.

Short Musculoskeletal Function Assessment: normative data of the Dutch population.

BACKGROUND: The Short Musculoskeletal Function Assessment (SMFA) is widely used in both research and clinical practice. Despite its frequent use, normative data of the SMFA have remained limited. Aim of this study was to gather normative data for the Dutch SMFA (SMFA-NL). METHODS: The SMFA-NL consists of two indices (function index and bother index) and four subscales (upper extremity dysfunction, lower extremity dysfunction, mental and emotional problems, and problems with daily activities). A total of 900 patients were invited to fill in the SMFA-NL. Six age groups (18-24, 25-34, 35-44, 45-54, 55-64, and 65-75 years) were constructed. Analysis of variance, t tests, and regression analyses were used to assess age and gender effects. RESULTS: The response rate was 97 %. There was a significant difference between men and women in scores on all indices and subscales (range p < 0.001 to p = 0.002), except for the upper extremity dysfunction subscale (p = 0.06). A significant interaction effect was found between gender and age for the upper extremity dysfunction subscale; a larger decrease in score with increasing age was observed for women, compared with men. Significant differences were found between age groups for the bother index (p < 0.001), lower extremity dysfunction subscale (p = 0.001), and the problems with daily activities subscale (p = 0.002). CONCLUSION: Significant differences in SMFA-NL scores were found between men and women and between different age groups. These SMFA-NL normative data provide an opportunity of benchmarking health status of participants with musculoskeletal disorders or injuries against their age- and gender-matched peers in the Dutch population.

Construct and concurrent validity of a Nintendo Wii video game made for training basic laparoscopic skills.

BACKGROUND: Virtual reality (VR) laparoscopic simulators have been around for more than 10 years and have proven to be cost- and time-effective in laparoscopic skills training. However, most simulators are, in our experience, considered less interesting by residents and are often poorly accessible. Consequently, these devices are rarely used in actual training. In an effort to make a low-cost and more attractive simulator, a custom-made Nintendo Wii game was developed. This game could ultimately be used to train the same basic skills as VR laparoscopic simulators ought to. Before such a video game can be implemented into a surgical training program, it has to be validated according to international standards. METHODS: The main goal of this study was to test construct and concurrent validity of the controls of a prototype of the game. In this study, the basic laparoscopic skills of experts (surgeons, urologists, and gynecologists, n = 15) were compared to those of complete novices (internists, n = 15) using the Wii Laparoscopy (construct validity). Scores were also compared to the Fundamentals of Laparoscopy (FLS) Peg Transfer test, an already established assessment method for measuring basic laparoscopic skills (concurrent validity). RESULTS: Results showed that experts were 111 % faster (P = 0.001) on the Wii Laparoscopy task than novices. Also, scores of the FLS Peg Transfer test and the Wii Laparoscopy showed a significant, high correlation (r = 0.812, P < 0.001). CONCLUSIONS: The prototype setup of the Wii Laparoscopy possesses solid construct and concurrent validity.

What is the long-term clinical outcome after fragility fractures of the pelvis? - A CT-based cross-sectional study.

BACKGROUND: Recently, Rommens and Hoffman introduced a CT-based classification system for fragility fractures of the pelvis (FFP). Although fracture characteristics have been described, the relationship with clinical outcome is lacking. The purpose of this study was to get insight into the type of treatment and subsequent clinical outcome after all types of FFP. METHODS: A cross-sectional cohort study was performed including all elderly patients (≥ 65 years) with a CT-diagnosed FFP, between 2007-2019 in two level 1 trauma centers. Data regarding treatment, mortality and clinical outcome was gathered from the electronic patient files. Patients were asked to complete patient-reported outcome measures (PROMs) regarding physical functioning (SMFA) and quality of life (EQ-5D). Additionally, a standardized multidisciplinary treatment algorithm was constructed. RESULTS: A total of 187 patients were diagnosed with an FFP of whom 117 patients were available for follow-up analysis and 58 patients responded. FFP type I was most common (60%), followed by type II (27%), type III (8%) and type IV (5%). Almost all injuries were treated non-operatively (98%). Mobility at six weeks ranged from 50% (type III) to 80% type II). Mortality at 1 year was respectively 16% (type I and II), 47% (type III) and 13% (type IV). Physical functioning (SMFA function index) ranged from 62 (type III and IV) to 69 (type II) and was significantly decreased (P=<0.001) compared to the age-matched general population. Quality of life was also significantly decreased, ranging from 0.26 (type III) to 0.69 (type IV). CONCLUSIONS: FFP type I and II are most common. Treatment is mainly non-operative, resulting in good mobility after six weeks, especially for patients with FFP type I and II. Mortality rates at one year were substantial in all patients. Physical functioning and quality of life was about 20-30% decreased compared to the general population.

Loss of enterocyte mass is accompanied by diminished turnover of enterocytes after myeloablative therapy in haematopoietic stem-cell transplant recipients.

BACKGROUND: Intestinal mucosal barrier injury (MBI), resulting from myeloablative conditioning for haematopoietic stem-cell transplantation (HSCT), is an important cause of morbidity. Despite its frequency, recognition presents a challenge, while the aetiology needs still to be unravelled. The relationship between enterocyte mass and enterocyte loss was explored by examining citrulline serum levels and by assessing circulating intestinal fatty acid-binding protein (I-FABP) and ileal bile acid-binding protein (I-BABP), proteins released by dying mature enterocytes. PATIENTS AND METHODS: Thirty-four adult patients with haematological malignancy received allogeneic HSCT (HSCT day 0) 12 days after being given idarubicin, cyclophosphamide and total body irradiation as myeloablative conditioning, a regimen known to induce oral and intestinal MBI. Serum levels of citrulline, I-FABP and I-BABP were measured on HSCT days -12, -6, 0, +7, +14 and +21. RESULTS: Myeloablative conditioning resulted in a significant decrease in serum citrulline with the nadir on HSCT day +7; thereafter, levels rose gradually. Simultaneously, a significant decrease in I-FABP and I-BABP levels occurred from the day of transplant until day +14. CONCLUSIONS: Simultaneous reduction and subsequent increase of citrulline and I-FABP and I-BABP levels following cytotoxic treatment show that enterocyte mass corresponds to lower rate of dying enterocytes, indicating reduced turnover of enterocytes. Assessment of enterocyte turnover and mass offers opportunities for evaluation of new MBI therapies.

Leucocyte and platelet adhesion in different layers of the small bowel during experimental total warm ischaemia and reperfusion.

BACKGROUND: Ischaemia and reperfusion (IR) of the small bowel is involved in many clinical conditions. A key component in IR-induced tissue damage is microvascular dysfunction. The aim was to investigate the role of leucocytes and platelets in capillary flow impediment and tissue damage. METHODS: Anaesthetized rats were subjected to 30 min warm ischaemia of the small bowel, followed by 1 h reperfusion. To elucidate the influence of leucocytes on platelet adhesion, leucocyte-vessel wall interactions induced by IR were prevented by anti-platelet activating factor (PAF) or anti-intercellular adhesion molecule (ICAM)-1. Intravital videomicroscopy was performed and tissue injury was evaluated histologically. RESULTS: In submucosal venules, IR induced an increase in the median number of interacting leucocytes from 3 to 10 and 20 leucocytes per 100-microm venule segment after 10 and 60 min reperfusion respectively. Anti-PAF or anti-ICAM-1 completely attenuated this increase, resulting in an eightfold improvement in submucosal capillary flow and reduced tissue injury. Shedding of villi no longer occurred. Platelet-vessel wall interactions occurred particularly in submucosal venules, but were not affected by anti-PAF or anti-ICAM-1. CONCLUSION: Small bowel IR initiated an inflammatory and thrombotic response in the submucosal layer only. Attenuation of leucocyte adhesion improved submucosal capillary perfusion, preventing shedding of mucosal villi.

Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality.

BACKGROUND: During the 1980s, the incidence of primary malignant brain and other central nervous system tumors (hereafter called brain cancer) was reported to be increasing among all age groups in the United States, while mortality was declining for persons younger than 65 years. We analyzed these data to provide updates on incidence and mortality trends for brain cancer in the United States and to examine these patterns in search of their causes. METHODS: Data on incidence, overall and according to histology and anatomic site, and on relative survival were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for 1975 through 1995. Mortality data were obtained from the National Center for Health Statistics. Medicare procedure claims from the National Cancer Institute's SEER-Medicare database were used for imaging trends. Statistically significant changes in incidence trends were identified, and annual percent changes were computed for log linear models. RESULTS/CONCLUSIONS: Rates stabilized for all age groups during the most recent period for which SEER data were available, except for the group containing individuals 85 years of age or older. Mortality trends continued to decline for the younger age groups, and the steep increases in mortality seen in the past for the elderly slowed substantially. Patterns differed by age group according to the site and grade of tumors between younger and older patients. During the last decade, use of computed tomography scans was relatively stable for those 65-74 years old but increased among those 85 years old or older. IMPLICATIONS: Improvements in diagnosis and changes in the diagnosis and treatment of elderly patients provide likely explanations for the observed patterns in brain cancer trends.

Agricultural pesticide use and risk of glioma in Nebraska, United States.

BACKGROUND: To evaluate the risk of the adult glioma associated with farming and agricultural pesticide use, the authors conducted a population based case control study in eastern Nebraska. METHODS: Telephone interviews were conducted with men and women diagnosed with gliomas (n = 251) between 1988 and 1993 and controls (n = 498) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds upon reaction with nitrite). Non-farmers were used as the reference category for all analyses. RESULTS: Among men, ever living or working on a farm and duration of farming were associated with significantly increased risks of glioma (> or =55 years on a farm OR = 3.9, 95% CI 1.8 to 8.6); however, positive findings were limited to proxy respondents. Among women, there were no positive associations with farming activities among self or proxy respondents. Specific pesticide families and individual pesticides were associated with significantly increased risks among male farmers; however, most of the positive associations were limited to proxy respondents. For two herbicides and three insecticides, use was positively associated with risk among both self and proxy respondents. Based on a small number of exposed cases, ORs were significantly increased for the herbicides metribuzin (OR = 3.4, 95% CI 1.2 to 9.7) and paraquat (OR = 11.1, 95% CI 1.2 to 101), and for the insecticides bufencarb (OR = 18.9, 95% CI 1.9 to 187), chlorpyrifos (OR = 22.6, 95% CI 2.7 to 191), and coumaphos (OR = 5.9, 95% CI 1.1 to 32). CONCLUSION: The authors found significant associations between some specific agricultural pesticide exposures and the risk of glioma among male farmers but not among female farmers in Nebraska; however, most of the positive associations were limited to proxy respondents. These findings warrant further evaluation in prospective cohort studies where issues of recall bias are not a concern.

The effect of acute alcohol intoxication on gut wall integrity in healthy male volunteers; a randomized controlled trial.

The aim of the study is to determine the effect of acute alcohol consumption on enterocytes. Chronic alcohol consumption has been known to induce a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol-induced liver disease. Data on the extent of the damage induced by acute alcohol consumption in healthy human beings is scarce. Studies show that heavy incidental alcohol consumption is a growing problem in modern society. Data on this matter may provide insights into the consequences of this behavior for healthy individuals. In a randomized clinical trial in crossover design, 15 healthy volunteers consumed water one day and alcohol the other. One blood sample was collected pre-consumption, five every hour post-consumption, and one after 24 h. Intestinal fatty acid binding protein (I-FABP) was used as a marker for enterocyte damage. Liver fatty acid binding protein (L-FABP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were used as markers for hepatocyte damage. Lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) were used as a measure of translocation. Interleukin-6 (IL-6) was used to assess the acute inflammatory response to endotoxemia. Alcohol consumption caused a significant increase in serum I- and L-FABP levels, compared to water consumption. Levels increased directly post-consumption and decreased to normal levels within 4 h. LBP, sCD14, and IL-6 levels were not significantly higher in the alcohol group. Moderate acute alcohol consumption immediately damages the enterocyte but does not seem to cause endotoxemia.

Parental occupational exposure to hydrocarbons and risk of acute lymphocytic leukemia in offspring.

Parental exposure to hydrocarbons at work has been suggested to increase the risk of childhood leukemia. Evidence, however, is not entirely consistent. Very few studies have evaluated the potential parental occupational hazards by exposure time windows. The Children's Cancer Group recently completed a large-scale case-control study involving 1842 acute lymphocytic leukemia (ALL) cases and 1986 matched controls. The study examined the association of self-reported occupational exposure to various hydrocarbons among parents with risk of childhood ALL by exposure time window, immunophenotype of ALL, and age at diagnosis. We found that maternal exposure to solvents [odds ratio (OR), 1.8; 95% confidence interval (CI), 1.3-2.5] and paints or thinners (OR, 1.6; 95% CI, 1.2-2.2) during the preconception period (OR, 1.6; 95% CI, 1.1-2.3) and during pregnancy (OR, 1.7; 95% CI, 1.2-2.3) and to plastic materials during the postnatal period (OR, 2.2; 95% CI, 1.0-4.7) were related to an increased risk of childhood ALL. A positive association between ALL and paternal exposure to plastic materials during the preconception period was also found (OR, 1.4; 95% CI, 1.0-1.9). The ALL risk associated with parental exposures to hydrocarbons did not vary greatly with immunophenotype of ALL. These results suggest that the effect of parental occupational exposure to hydrocarbons on offspring may depend on the type of hydrocarbon and the timing of the exposure.

Modification of allograft survival in rats by blood transfusion to the donor.

In the BN/Ro-to-WAG/Ro rat donor-host combination, third-party blood transfusions given to the donor shortly before transplantation can markedly influence heart allograft survival if the immune response of the recipient has been modulated. The WAG recipients were either transfused with BN donor blood, which leads to a permanent graft survival, or postoperatively treated with a single i.m. injection of 15 mg/kg cyclosporine, which leads to a moderate prolongation of graft survival. In the transfused recipients, blood transfusions to the donor had a detrimental influence on graft survival. In the cyclosporine-treated recipients, blood transfusions to the donor had a beneficial effect. There was no significant difference in graft survival after a single transfusion or multiple transfusions to the donor. Recipient-type blood transfusion to the donor did not influence graft survival, nor did irradiated third-party blood or third-party erythrocytes. However, third-party leukocyte suspensions had a significant influence on heart allograft survival. It is concluded that third-party viable leukocytes are responsible for the induction of the donor transfusion phenomenon. It is also postulated that the third-party leukocytes interact with the dendritic cell population of the graft, leading to a reduction in its immunogenicity.

The limited efficacy of cyclosporine in preventing rejection and graft-versus-host disease in orthotopic small bowel transplantation in rats.

The effect of different schedules of cyclosporine treatment on the survival of small bowel allografts was studied in rats. The administration of a short course of CsA (15 mg/kg on days 0, 1, 2, 4, and 6) had no beneficial effect on graft-vs.-host disease and survival time of the recipient compared with untreated controls. CsA, 25 mg/kg for 1 or 2 weeks prolonged survival significantly (38.3 +/- 3.8 and 42.5 +/- 2.7 vs. 16.6 +/- 2.7, P less than 0.01). When combined with maintenance therapy, 15 mg/kg of CsA 3 times weekly until day 100, only 7 of 30 rats survived more than 100 days. In addition, GVHD was not consistently abrogated in these groups. Only high doses of CsA (25 mg/kg on days 0-6, 15 mg/kg on days 7-13, followed by maintenance therapy) could prevent the onset of GVHD, although the survival time of the transplants was not prolonged compared with untreated controls due to a toxic side effect of CsA on the transplants. It can be concluded that CsA used as monotherapy is ineffective in consistently ameliorating GVHD and rejection in the WAG-BN rat model. This model exhibits at least some of the immunological problems seen in large animal models and can be useful in studying combinations of immunosuppressive drugs or methods that may be applicable to small bowel transplantation in man.

Small bowel transplantation in rats. The effect of pretransplant donor-specific blood transfusions on various segments of small bowel grafts.

The effects of pretransplant donor-specific blood transfusion on the survival of orthotopic small bowel transplants in rats were investigated in the fully allogeneic BN (Rt1n) to WAG (Rt1u) donor-host combination. Previous studies show that in this combination DSTs lead to permanent survival of heterotopically transplanted hearts, marked prolongation of kidney grafts, and moderate prolongation of pancreas grafts but have no effect on skin grafts. Without pretreatment, total small bowel grafts (+/- 45 cm) were rejected in 12.2 +/- 1.8 days (mean +/- SD), and 10-cm segments of jejunum or ileum in 11.2 +/- 4.0 and 11.6 +/- 0.5 days, respectively. Three DSTs given on days -21, -14, and -7 before transplantation had no effect on graft survival in any of the groups tested. Total small bowel grafts were rejected in 12.8 +/- 2.5 days, and 10-cm-long segments or jejunum or ileum in 17.0 +/- 7.2 days and 11.5 +/- 2.7 days, respectively. Graft-versus-host disease, which was mild and transient, occurred in 50% of the nontreated rats engrafted with a total small bowel, in 40% of the animals transplanted with an ileum segment, and in none of the rats that received a jejunal transplant. In the DST-pretreated groups, none of the animals transplanted with a total small bowel or ileum segment and 16.6% of the animals transplanted with a jejunum segment showed clinical signs of GVHD. When DST pretreatment was combined with cyclosporine, grafts did not survive any longer than with cyclosporine treatment alone. It is concluded that DSTs ameliorate GVHD but do not prolong the survival of small bowel allografts nor act additively with cyclosporine treatment.

Total orthotopic allogeneic small bowel transplantation in rats. Attempts to ameliorate the graft-versus-host disease by irradiation and transfusions of the donor.

The effect of pretransplant specific blood transfusions and irradiation of the donor were studied in total orthotopic small bowel transplantation in rats, with the aim of ameliorating the graft-versus-host reaction. Syngeneic transplantation with or without irradiation of the donor with 10 Gy showed that small bowel transplantation is compatible with a normal nutritional status, when no rejection is involved. Transplantation in the histoincompatible WAG-to-BN combination without pretreatment resulted in rejection of the small bowel grafts in 16.6 +/- 2.7 days. Pretreatment with 3 BN blood transfusions to the WAG donor did not prolong the survival time; surprisingly, the transfusions induced a more-severe GVH reaction. Irradiation of the donor with 10 Gy was very effective in ameliorating the GVH disease, but the absence of the immunosuppressive effect of the GVH disease did lead to an accelerated graft rejection (7.5 +/- 0.9 days).

Involvement of endogenous interleukin-10 and tumor necrosis factor-alpha in renal ischemia-reperfusion injury.

BACKGROUND: Ischemia followed by reperfusion is a common clinical event associated with a pro-inflammatory response leading to organ dysfunction. The aim of the present study is to evaluate the interplay between this pro-inflammatory response and apoptosis. We investigated the role of the pro-inflammatory mediator tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory mediator interleukin-10 (IL-10) in inflammation and apoptosis after renal ischemia reperfusion. METHODS: Male Swiss mice were subjected to 45 min of ischemia followed by reperfusion and subsequently administered neutralizing Abs against either TNF-alpha (TN3), IL-10 (JES5-2A5) or control. RESULTS: After 1 day of reperfusion, anti-TNF-alpha treatment reduced whereas anti-IL-10 treatment exacerbated postischemic renal injury, inflammation, and, to a lesser extent, apoptosis as measured by changes in blood urea nitrogen content, immunohistologically detectable renal TNF-alpha protein and neutrophils, histological integrity of renal parenchyma, and DNA ladder formation. Furthermore, anti-IL-10 treatment enhanced major histocompatibility complex class I and II expression at day 7 as measured by enzyme immunoassay and immunohistology. CONCLUSIONS: These data indicate that the extent of reperfusion-induced apoptosis is modulated by the inflammatory response, during which locally produced TNF-alpha plays a significant role in the development of tissue injury. Subsequently, this pro-inflammatory reaction is followed by endogenous production of the anti-inflammatory cytokine IL-10, which serves as a physiological counterbalance to the effects of TNF-alpha. These novel pathophysiological insights may provide new basis for the development of tools for limiting ischemia and reperfusion injury.

Long-term survival of DLA-matched segmental small-bowel allografts in dogs.

The aim of this study was to investigate the combined effect of DLA matching and immunosuppressive therapy on the survival of segmental small-bowel allografts in dogs. Orthotopic segmental small-bowel transplantations (25 to 30% of total small bowel length) were performed in two stages: first a heterotopic segmental small bowel transplantation, followed after 5 to 8 weeks by a second-stage operation during which the heterotopic graft was placed in an orthotopic position and the native small bowel was resected. All dogs received cyclosporine immunosuppression. Control dogs (n = 4), subjected to total enterectomy, survived 37.3 +/- 7.1 days (mean +/- SEM). Recipients of DLA-mismatched small bowel grafts (n = 6) survived 113.2 +/- 37.0 days, which was a significantly shorter time than dogs with a DLA-matched graft (n = 6, 211.5 +/- 38.8 days, P < 0.05). None of the matched allografts was rejected during CsA treatment, whereas four of six mismatched grafts were (P < 0.05). The control dogs uniformly showed progressive weight loss, steatorrhea, and hypoalbuminemia. The dogs with DLA-mismatched grafts did not regain initial body weight, whereas animals with DLA-matched grafts recovered preoperative weight after 20 weeks. Both transplanted groups showed near-normal fecal fat excretions and constant serum albumin, cholesterol, and triglyceride levels, whereas serum total protein levels increased during follow-up. We conclude that segmental small bowel transplantation between DLA-matched donor-recipient pairs results in long-term survivors with an adequate nutritional status. This may have important implications for future living-related small-bowel transplantation.

Detection of canine intestinal allograft rejection by in vivo electrophysiologic monitoring.

The aim of this study was to evaluate the significance of in vivo measurements of electrophysiologic parameters for the detection of canine small bowel (SB) allograft rejection. In dogs of group I (n = 17) a heterotopic SB autotransplantation was performed. Dogs of group II (n = 8) received a heterotopic SB allograft in a fully mismatched donor-recipient combination. No immunosuppression was given. All grafts were monitored regularly by in vivo measurements of transepithelial potential differences (PDs) and by biopsies of the grafts. The overall technical failure rate was 36% caused by thrombosis at the vascular anastomosis in most cases. All successful autografts survived the experimental period and showed physiologic PD responses after stimulation by both a theophylline solution and a glucose solution. The successful allografts survived 5.5 +/- 0.2 days (mean +/- SEM); the transepithelial PDs showed normal responses at postoperative day 3, but showed decreased responses at day 5 (P less than 0.05) and reversed responses at day 6 (P less than 0.05). The diminished PD responses correlated well with the onset of histologic alterations characteristic of rejection. This study demonstrates that serial monitoring of transepithelial PD responses is a noninvasive method to detect acute SB allograft rejection.

Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys.

Non-heart-beating (NHB) donors are a valuable source of kidneys for transplantation. The organs, however, sustain substantial warm ischemic damage that may jeopardize the transplantability and result in nonfunction of the grafts. Quantification of warm ischemic time (WIT) and prediction of transplant outcome are essential for the use of NHB donor organs. During machine preservation (MP) the viability of NHB donor kidneys was evaluated through calculating intrarenal vascular resistance and determining lactate dehydrogenase and alpha-glutathione S-transferase (alphaGST) in the perfusate. Thirty-seven functioning (F) and nine nonfunctioning kidneys (NF) were compared. WIT was longer in NF; serum creatinine, donor age, and preservation time were not different. WIT correlated well with alphaGST after 4 and 8 hr of MP (r=0.353, P=0.009, and r=0.346, P=0.011, respectively). When compared with F, intrarenal vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05); at all time points, alphaGST levels were elevated in NF (P<0.05). Lactate dehydrogenase activity was not different between the groups, but could identify immediate functioning grafts within the F group. In conclusion, alphaGST levels correlated strongly with WIT and were also able to distinguish NF from F grafts. alphaGST can adequately predict the functional outcome of NHB donor grafts before transplantation; levels of alphaGST can be used to define reliable safety margins for viability. Therefore, MP is useful in evaluating the viability of NHB donor kidneys, and the parameters discussed will help to select nonviable grafts from this valuable pool of kidneys for transplantation.