The Role of Regulatory Cells in Miniature Swine Rendered Tolerant to Cardiac Allografts by Donor Kidney Cotransplantation

To determine the mechanism by which cotransplantation of a kidney allograft induces tolerance to a donor heart in miniature swine, we examined the role of CD25⁺ cells in heart/kidney recipients. Tolerance was induced to class‐I MHC mismatched hearts by cotransplanting a donor‐specific kidney with a 12‐day course of cyclosporine. Peripheral blood leukocytes (PBL) were isolated from tolerant heart/kidney recipients and used in cell‐mediated lympholysis (CML) coculture assays as either unmodified PBL, PBL enriched for CD25⁺ cells or PBL depleted of CD25⁺ cells to assess their ability to suppress CML responses of naïve recipient‐matched leukocytes against mismatched target cells. Primed PBL from tolerant heart/kidney recipients completely suppressed lysis by naïve cells. Complete suppression of the response of naïve recipient‐matched leukocytes against donor‐matched target cells was lost following the depletion of CD25⁺ cells from tolerant heart/kidney animal PBL, but it was reestablished by incubation of naïve cells with small populations of CD25⁺ cells from tolerant heart/kidney animals. These data suggest that peripheral blood from tolerant heart/kidney recipients contains regulatory cells that, upon priming, can suppress the response of naïve‐matched PBL in coculture CML assays, and that suppression appears to be dependent on cells expressing CD25.     

Gastrointestinal transit after laparoscopic versus open colonic resection

Background: Multimodal rehabilitation with epidural analgesia, early oral nutrition and mobilization, and laxative use has decreased the duration of ileus after colonic surgery to about 2 days, as compared with the usual 3 to 5 days of rehabilitation required after open surgery and the slightly shorter time required with laparoscopic surgery. Gastrointestinal transit after colonic resection with laparoscopy or laparotomy was assessed. Methods: In this study, 32 patients randomized to laparoscopic or open colonic resection received 4 MBq of ¹¹¹indium diethylenetriamine pentaacetic acid, a tracer, at the end of surgery. Images of the abdomen were obtained 24 and 48 h postoperatively. An opaque abdominal dressing blinded care personnel and patients to the procedure. Results: Defecation occurred on median day 2 postoperatively in both groups. At 48 h postoperatively, 53% of the tracer was excreted by patients in the laparoscopic group, as compared with 26% in the open group (p > 0.05). Conclusion: Postoperative ileus and gastrointestinal transit normalized within 48 h after colonic resection in the patients who received multimodal rehabilitation. No significant difference was observed between the patients who underwent the laparoscopic procedure and those who underwent the open procedure. Supported by Danish Pharmacy Foundation of 1991 and the Danish Research Council 9902757     

Tranexamic acid given intraoperatively reduces blood loss after total knee replacement: a randomized,controlled study

BACKGROUND: Extensive blood loss in total knee replacement (TKR) surgery is well known and is associated with a high transfusion rate of allogenic blood. Tranexamic acid (TXA) has been shown to reduce blood loss by 50% in this patient group, but only in cases with a perioperative loss of 1400-1800 ml. This study was performed to see if TXA offers any advantages in knee replacement surgery with blood loss at 800 ml. METHODS: Thirty consecutive patients scheduled for TKR in spinal anesthesia with the use of a tourniquet, were randomized to TXA or non-TXA. Tranexamic acid 10 mg kg-1 was given at conclusion of surgery and again 3 h later. Blood loss was registered. RESULTS: Total blood loss was at all times significantly lower in the TXA group compared to the non-TXA group (409.7+/-174.9 ml vs. 761.7+/-313.1 ml; P<0.001). There were no differences in coagulation parameters. No patients in the TXA group had a blood transfusion vs. 13% in the non-TXA group (NS). No complications were registered in the two groups. CONCLUSION: We conclude that TXA significantly reduces blood loss after total knee replacement surgery.     

Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy: a nationwide Danish cohort study

Objectives: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT. Methods: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring. Results: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0–12] years and 6 [0–13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30?mm [15–53] vs. 25?mm [3–44], p?p?Discussion: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research.     

Bioimpedance as a measure of fluids in patients with septic shock. A prospective observational study

Background

Septic shock is often treated with aggressive fluid resuscitation leading to profound fluid overload. The assessment of fluid status relies on suboptimal measures making treatment difficult. Bioelectrical impedance analysis is an alternative but the validity is unclear. The aim of this study was to determine the validity of bioelectrical impedance analysis for fluid measures in patients with septic shock.

Methods

Single-center, prospective observational cohort study. We included adult ICU patients with septic shock. We evaluated the agreement between measures on the left and right side of the patient and measures 1 h apart by two bioelectrical impedance devices. Results are presented as Bland Altman plots with 95% Limits of Agreements (LoA) and as correlations between bioelectrical impedance analysis results and clinical markers of fluids.

Results

Forty-nine patients were included. The agreement between measures on the left and the right side of the patient and after 1 h was overall without bias, but with wide LoA's. Fluid overload 1 h apart showed the most narrow 95% LoA (−2.4–2.9 L). The same wide limits of agreements were observed when comparing devices. For example, total body water with 95% LoA of −14.8 –16.7 L. Correlations between bioelectrical impedance analysis and clinical measures were low but statistically significant.

Conclusions

In patients with septic shock bioelectrical impedance analysis had no systematic errors or bias, but wide limits of agreement, indicating that the devices have a large and uncorrectable random error. Fluid status by bioelectrical impedance analysis is not sufficiently accurate to guide treatment in this group of patients.     

Estimating the organ donor potential in Denmark: a prospective analysis of deaths in intensive care units in northern Denmark

To estimate the organ donor potential in Denmark we conducted a prospective registration of deaths in all intensive care units (ICUs), counting 15 ICUs and two neurosurgical ICUs in the four northern Danish counties, which cover a population of 1.64 million inhabitants or 30% of the Danish population. From September 1, 2000 till August 31, 2002, all deaths in the ICUs in 15 hospitals were recorded. Each case was evaluated locally postmortem with respect to medical suitability to organ donation. A total of 1655 deaths were recorded, corresponding to 504 deaths per million population per year (PMP). Median age was 70 years (0 to 99 years), 52% were more than 70 years, and 22% more than 80 years of age. The cause of death was cerebral lesion in 18% of the cases (neurosurgical ICUs: n = 182; ICUs: n = 110). By thorough medical record examination, the number of potential donors was estimated to be 169, corresponding to 51 PMP. The cause of death was cerebral lesion in 96% of the potential donors. Organ donation was performed in 43 cases (32 from neurosurgical ICUs and 11 from ICUs) or 13.1 PMP. Thus, 25% of the potential became organ donors. The major reason for nondonation was refusal from the relatives. Out of 127 questioned, the relatives refused in 62 cases (49%). By comparison, 74% of the general Danish population are willing to donate organs after death. The rate of nondetection of potential donors by the hospital staff could be estimated to 22%. In conclusion, the organ donor potential may allow for improvement in donation rates. An increased effort for donor hospitals is warranted. The motives for refusal by the relatives need elucidation.     

Attitudes, knowledge, and proficiency in relation to organ donation: a questionnaire-based analysis in donor hospitals in northern Denmark

The aim of this study was to assess knowledge, attitudes, and proficiency in relation to organ donation among staff members of intensive care units (ICUs) in donor hospitals, and possibly identify areas for improvement. The investigation was carried out as a collaboration between the transplant center and appointed key persons in all 17 ICUs in 15 hospitals in northern Denmark. A total of 1168 structured questionnaires were distributed to the health care professionals in the ICUs in the region; 689 were returned, giving a response rate of 59%. In general, there is a positive attitude among health care professionals toward organ donation. However, a considerable fraction of 11% declares to be against organ donation. Only 49% of the ICU health care professionals are willing to donate their own organs after death. By comparison, 74% of the general Danish population are willing to donate organs after death. Doctors are more positive toward organ donation than the nursing staff. Thus, 95% of the doctors are positive to organ donation compared to 81% of the nurses; 70% of the doctors will donate own organs after death compared to 45% of the nurses. Further, the survey demonstrates as expected a significant lack of experience in organ donation. Our data show a considerable need for more education and training, especially on how to inform and support the donor relatives and how to identify potential donors. The survey also discloses a substantial need for information regarding the results of transplantation.     

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.     

Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood

Context  Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown. Objective  To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years. Design and Setting  Population-based, prospective, cohort study conducted in Sisimiut, Greenland. Participants  Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance. Main Outcome Measure  Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles. Results  A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively. Conclusion  These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.