Influenza activity in Europe during eight seasons (1999-2007): an evaluation of the indicators used to measure activity and an assessment of the timing, length and course of peak activity (spread) across Europe.

BACKGROUND: The European Influenza Surveillance Scheme (EISS) has collected clinical and virological data on influenza since 1996 in an increasing number of countries. The EISS dataset was used to characterise important epidemiological features of influenza activity in Europe during eight winters (1999-2007). The following questions were addressed: 1) are the sentinel clinical reports a good measure of influenza activity? 2) how long is a typical influenza season in Europe? 3) is there a west-east and/or south-north course of peak activity ('spread') of influenza in Europe? METHODS: Influenza activity was measured by collecting data from sentinel general practitioners (GPs) and reports by national reference laboratories. The sentinel reports were first evaluated by comparing them to the laboratory reports and were then used to assess the timing and spread of influenza activity across Europe during eight seasons. RESULTS: We found a good match between the clinical sentinel data and laboratory reports of influenza collected by sentinel physicians (overall match of 72% for +/- 1 week difference). We also found a moderate to good match between the clinical sentinel data and laboratory reports of influenza from non-sentinel sources (overall match of 60% for +/- 1 week). There were no statistically significant differences between countries using ILI (influenza-like illness) or ARI (acute respiratory disease) as case definition. When looking at the peak-weeks of clinical activity, the average length of an influenza season in Europe was 15.6 weeks (median 15 weeks; range 12-19 weeks). Plotting the peak weeks of clinical influenza activity reported by sentinel GPs against the longitude or latitude of each country indicated that there was a west-east spread of peak activity (spread) of influenza across Europe in four winters (2001-2002, 2002-2003, 2003-2004 and 2004-2005) and a south-north spread in three winters (2001-2002, 2004-2005 and 2006-2007). CONCLUSION: We found that: 1) the clinical data reported by sentinel physicians is a valid indicator of influenza activity; 2) the length of influenza activity across the whole of Europe was surprisingly long, ranging from 12-19 weeks; 3) in 4 out of the 8 seasons, there was a west-east spread of influenza, in 3 seasons a south-north spread; not associated with type of dominant virus in those seasons.

Internet-based monitoring of influenza-like illness (ILI) in the general population of the Netherlands during the 2003-2004 influenza season.

BACKGROUND: An internet-based survey of influenza-like illness (ILI)--the Great Influenza Survey or GIS--was launched in the Netherlands in the 2003-2004 influenza season. The aim of the present study was to validate the representativeness of the GIS population and to compare the GIS data with the official ILI data obtained by Dutch GPs participating in the Dutch Sentinel Practice Network. METHOD: Direct mailings to schools and universities, and repeated interviews on television and radio, and in newspapers were used to kindle the enthusiasm of a broad section of the public for GIS. Strict symptomatic criteria for ILI were formulated with the assistance of expert institutes and only participants who responded at least five times to weekly e-mails asking them about possible ILI symptoms were included in the survey. Validation of GIS was done at different levels: 1) some key demographic (age distribution) and public health statistics (prevalence of asthma and diabetes, and influenza vaccination rates) for the Dutch population were compared with corresponding figures calculated from GIS; 2) the ILI rates in GIS were compared with the ILI consultation rates reported by GPs participating in the Dutch Sentinel Practice Network. RESULTS: 13,300 persons (53% of total responders), replied at least five times to weekly e-mails and were included in the survey. As expected, there was a marked under-representation of the age groups 0-10 years and 81->90 years in the GIS population, although the similarities were remarkable for most other age groups, albeit that the age groups between 21 and 70 years were slightly overrepresented. There were striking similarities between GIS and the Dutch population with regard to the prevalence of asthma (6.4% vs. 6.9%) and the influenza vaccination rates, and to a lesser degree for diabetes (2.4% vs. 3.5%). The vaccination rates in patients with asthma or diabetes, and persons older than 65 years were 68%, 85%, and 85% respectively in GIS, while the corresponding percentages in the Dutch population were 73%, 85% and 87%. There was also a marked similarity between the seasonal course of ILI measured by GIS and the GPs. Although the ILI rate in GIS was about 10 times higher, the curves followed an almost similar pattern, with peak incidences occurring in the same week. CONCLUSION: The current study demonstrates that recruitment of a high number of persons willing to participate in on-line health surveillance is feasible. The information gathered proved to be reliable, as it paralleled the information obtained via an undisputed route. We believe that the interactive nature of GIS and the appealing subject were keys to its success.

Icodextrin reduces postoperative adhesion formation in rats without affecting peritoneal metastasis.

BACKGROUND: Peroperative peritoneal trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative adhesion formation. The same cascade seems to play a role in the process of intra-abdominal tumor recurrence. Icodextrin is a glucose polymer solution that is absorbed slowly from the peritoneal cavity, allowing prolonged "hydroflotation" of the viscera, thereby decreasing adhesion formation. This study evaluated the adhesion-preventing properties of icodextrin and its effect on peritoneal metastasis. METHODS: Reproducible rat models of peritoneal trauma were used, allowing semiquantitative scoring of adhesion formation or tumor load. In one experiment, peritoneal trauma was inflicted; one group was treated by peroperative intra-abdominal instillation of 7.5% icodextrin, one by instillation of RPMI (placebo), and one had no instillate (controls). In another experiment involving a different model of peritoneal trauma, the coloncarcinoma cell line CC531 was injected intraperitoneally to induce tumor load, again using these three groups. RESULTS: Treatment of peritoneally traumatized rats with icodextrin caused a 51% reduction in postoperative adhesion formation ( P < .001). However, peroperative intra-abdominal treatment with icodextrin did not affect intraperitoneal tumor cell adhesion and growth of free intra-abdominal tumor cells in rats with this model of severe peritoneal trauma. CONCLUSION: A 7.5% icodextrin solution is effective in reducing postoperative adhesions without promoting tumor recurrence and therefore may prove useful and safe in oncologic surgery.

The epidemiology of suicide and attempted suicide in Dutch General Practice 1983-2003.

BACKGROUND: Many patients attempting or committing suicide consult their general practitioner (GP) in the preceding period, indicating that GPs might play an important role in prevention. The aim of the present study was to analyse the epidemiology of suicidal behaviour in Dutch General Practice in order to find possible clues for prevention. METHOD: Description of trends in suicide and suicide attempts occurring from 1983-2003 in the Dutch General Practice Sentinel Network, representing 1% of the Dutch population. The data were analysed with regard to: 1) suicidal behaviour trends and their association with household situation; 2) presence of depression, treatment of depression and referral rate by GPs; 3) contact with GP before suicide or suicide attempt and discussion of suicidal ideation. RESULTS: Between 1983 and 2003 the annual number of suicide and suicide attempts decreased by 50%. Sixty percent of the patients who committed or attempted suicide were diagnosed as depressed, of whom 91% were treated by their GP with an antidepressant. Living alone was a risk factor for suicide (odds ratio 1.99; 95% CI 1.50 to 2.64), whereas living in a household of 3 or more persons was a relative risk for a suicide attempt (odds ratio 1.81; 95% CI 1.34 to 2.46). Referral to a psychiatrist or other mental health professionals occurred in 65% of the cases. GPs recalled having discussed suicidal ideation in only 7% of the cases, and in retrospect estimated that they had foreseen suicide or suicide attempts in 31% and 22% of the cases, respectively, if there had been contact in the preceding month. CONCLUSION: With regard to the prescription of antidepressants and referral of suicidal patients to a psychiatrist, Dutch GPs fulfil their role as gatekeeper satisfactorily. However, since few patients discuss their suicidal ideation with their GP, there is room for improvement. GPs should take the lead to make this subject debatable. It may improve early recognition of depressed patients at risk and accelerate their referral to mental health professionals.

The inhibitory effect of (111)In-DTPA(0)-octreotide on intrahepatic tumor growth after partial hepatectomy.

UNLABELLED: The aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with (111)In-diethylenetriaminepentaacetic acid (DTPA)(0)-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). METHODS: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 micro g/kg subcutaneously twice daily or with 370 MBq (111)In-DTPA(0)-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of (111)In-DTPA(0)-octreotide therapy on liver regeneration after PHx. RESULTS: PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. (111)In-DTPA(0)-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). (111)In-DTPA(0)-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, (111)In-DTPA(0)-octreotide therapy did not influence liver regeneration or liver function after PHx. CONCLUSION: Peptide receptor radionuclide therapy with (111)In-DTPA(0)-octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.

Frequencies of donor-reactive helper T lymphocytes correlate with rejection of aortic valve allografts in rats.

BACKGROUND AND AIMS OF THE STUDY: Human valve allografts are commonly used in cardiac surgery for congenital and acquired valve diseases. Particularly in the pediatric population, these allografts are prone to fail in the long term, and require replacement. In part, this failure may be due to immunological phenomena. The frequency of helper T lymphocytes (HTLf) measured in peripheral blood and spleen serves as a parameter for acute rejection in organ transplantation. The value of this parameter in valve transplantation was studied using the 'Rotterdam' implantation model in rats. METHODS: HTLf were determined in peripheral blood and spleen at seven and 21 days after allogeneic (WAG-->DA) and syngeneic (DA-->DA) implantation of an aortic valved conduit. Valve competence was tested pre-implantation, at days 7 and 21 after implantation, and after explantation using a retrograde saline injection. Explanted valves were examined histologically. RESULTS: At seven days after allogeneic valve transplantation, HTLf in spleen (median 71/10(6)), but not in peripheral blood (median 26/106) were significantly elevated. At 21 days after allogeneic transplantation, a significant increase in HTLf was seen in both peripheral blood (median 10(9)/10(6)) and spleen (median 92/10(6)). All five (100%) syngeneic grafts and five of seven (71%) allografts were competent at day 7. At day 21, all five syngeneic grafts (100%) and zero allografts (0%) remained competent (p = 0.01). Histologically, mononuclear cell infiltration into the allogeneic valve leaflets and in the vascular wall was observed at day 7. At day 21, valve leaflets appeared to be acellular and deformed. All syngeneic valve grafts retained normal morphology. CONCLUSION: After aortic valve allografting in the rat, HTLf correlate with valve dysfunction and histopathological signs of rejection. Therefore, HTLf-analysis may be a useful tool in monitoring the cellular immune response as an indicator for early graft dysfunction due to rejection in clinical valve transplantation.

Increased tumor growth after high pressure pneumoperitoneum with helium and air.

BACKGROUND: Tumor growth appears proportional to the pressure of carbon dioxide insufflation during laparoscopic surgery. Air and helium are alternative insufflation gases. The objective of this study is to assess tumor growth after air and helium insufflation at different pressures. METHOD: Ninety-six WAG rats were allocated to either air or helium. In both arms, rats were randomly exposed to a one hour gasless procedure, or to 4 mm Hg, 10 mm Hg, or 16 mm Hg insufflation. At the start of the procedure, 500,000 CC531 tumor cells were injected intraperitoneally. After three weeks, intraperitoneal tumor growth was assessed. RESULTS: Higher insufflation pressures were associated with greater tumor growth. No difference of tumor growth between air and helium insufflation was found. CONCLUSION: In this experimental model, insufflation pressure appeared to have a greater impact on tumor growth than the type of gas. Further studies are necessary but it seems prudent to recommend employment of lower insufflation pressures in laparoscopic oncologic surgery.

Irrigation of port sites: prevention of port site metastases?

INTRODUCTION: Port site metastases can occur when free viable tumor cells implant at trocar wounds. Irrigation of port sites with cytotoxic agents has been suggested to prevent port site metastases. The objective of this study is to assess whether tumor growth at port sites can be reduced by irrigation of these port sites. METHODS: WAG rats were insufflated with CO(2) for 20 minutes and 5 x 10(5) CC531 tumor cells were injected intraperitoneally. Port sites were irrigated after completion of the pneumoperitoneum with povidone-iodine, a mixture of taurolidine and heparin, or sodium chloride. Controls did not undergo any irrigation of port sites. In experiment 1, all 16 rats had all 4 irrigation modalities. In experiment 2, four groups of 20 rats had one type of irrigation on two trocar wounds. Tumor growth was evaluated 4 weeks after the procedure. RESULTS: No difference in tumor growth at trocar wounds was found between any type of irrigation and controls in both experiments. CONCLUSION: In this experimental model, no beneficial or adverse effects of irrigation of port sites could be shown.

Impact of temperature and humidity of carbon dioxide pneumoperitoneum on body temperature and peritoneal morphology.

BACKGROUND: The insufflation of cold gas during laparoscopic surgery exposes patients to the risk for hypothermia. The objectives of this study were to investigate whether heating or humidification of insufflation gas could prevent peroperative hypothermia in a rat model, and to assess whether the peritoneum was affected by heating or humidification of the insufflation gas. METHODS: Rats were exposed to insufflation with either cold, dry carbon dioxide CO2 (group I); cold, humidified CO2 (group II); warm, dry CO2 (group III); or warm, humidified CO2 (group IV); another group underwent gasless laparoscopy (group V). Core temperature and intraperitoneal temperature were registered in all animals during 120 minutes. Specimens of the parietal peritoneum were taken directly after desufflation and 2 and 24 hours after the procedure. All specimens were analyzed with scanning electron microscopy (SEM). RESULTS: During the 120-minute study period, core temperature and intraperitoneal temperature were significantly reduced in groups I, II, and III. In the animals that underwent warm, humidified insufflation (group IV) and the gasless controls (group V), intraoperative hypothermia did not develop. At SEM, retraction and bulging of mesothelial cells and exposure of the basal lamina were seen in the four insufflation groups (groups I-IV) and also in the gasless controls (group V). CONCLUSION: Insufflation with cold, dry CO2 may lower the body temperature during laparoscopic surgery. Hypothermia can be prevented by both heating and humidifying the insufflation gas. Changes of the peritoneal surface occur after CO2 insufflation, despite heating or humidifying, and also after gasless surgery.

Requests for euthanasia in general practice before and after implementation of the Dutch Euthanasia Act.

BACKGROUND: The Netherlands was the first country in the world to implement a Euthanasia Act in 2002. It is unknown whether legalizing euthanasia under strict conditions influences the number and nature of euthanasia requests. AIM: To investigate changes in the number of, and reasons for, requests for euthanasia in Dutch general practice after implementation of the Euthanasia Act. DESIGN OF STUDY: Retrospective dynamic cohort study comparing 5 years before (1998-2002) and 5 years after (2003-2007) implementation of the Act. METHOD: Standardised registration forms were used to collect data on requests for euthanasia via the Dutch Sentinel Practice Network. This network of 45 general practices is nationally representative by age, sex, geographic distribution, and population density. RESULTS: The mean annual incidence of requests before implementation amounted to 3.1/10,000 and thereafter to 2.8/10,000 patients. However, trends differed by sex. The number of requests by males decreased significantly from 3.7/10,000 to 2.6/10,000 (P = 0.008); the requests by females increased non-significantly from 2.6/10,000 to 3.1/10,000. Before and after implementation, cancer remained the major underlying disease for requesting euthanasia: 82% versus 77% for men; 73% versus 75% for females. Pain was a major reason for a request, increasing in the period before implementation (mean 27%), but declining in the period thereafter (mean 22%). Loss of dignity became a less important reason after implementation (from 18% to 10%, P = 0.04), predominantly due to a marked decrease in the number of females citing it as a reason (from 17% to 6%, P = 0.02). CONCLUSION: There was no increase in demand for euthanasia after implementation of the Euthanasia Act. Pain as a reason for requesting euthanasia showed an increasing trend before implementation, but declined thereafter. Loss of dignity as a reason declined, especially in females.

Opting-out systems: no guarantee for higher donation rates.

There are considerable differences in the number of organ donations between countries. It is assumed that opting-out systems have a significantly positive impact on the national organ donation rate. The aim of our study was to establish whether different consent systems explain the difference in organ donation rates between countries when taking into account the difference in relevant mortality rates. For this study, we compared data on donation and relevant mortality rates for 10 different countries as well as information on the existing consent systems. This international comparative study shows that there is a strong correlation between mortality rates and donation rates (Spearman's rho = 0.81 (P < 0.01). International comparative legal research has shown that the differences between decision systems are marginal. When the national organ donation rates are corrected for mortality rates, these findings are confirmed: the donor efficiency rate shows that opting-out systems do not automatically guarantee higher donation rates than opting-in systems.

Somatostatin receptor gene therapy combined with targeted therapy with radiolabeled octreotide: a new treatment for liver metastases.

OBJECTIVE: To evaluate the effect of peptide receptor radionuclide therapy (PRRT) on somatostatin receptor (SSR)-transfected colon carcinoma cells in a rat liver metastases model. SUMMARY BACKGROUND DATA: Previously the authors have shown highly effective therapy with PRRT of SSR-positive tumors. This treatment is SSR-mediated; successful treatment is seen only in SSR-positive tumors, with no effect in SSR-negative tumors. As many tumors lack this receptor, the idea arose to transfect SSR-negative tumor cells with an SSR gene to apply PRRT on these SSR-transfected tumor cells. METHODS: CC531 colon carcinoma cells (SSR-negative) were transfected in vitro with an SSR (subtype 2) gene (CC2B). Liver metastases were produced after intraportal injection of these tumor cells in rats. On day 7, animals were treated with 185 or 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate. After 21 days rats were killed and liver metastases were counted. RESULTS: Treatment with 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate showed a significant antitumor response in rats with CC2B liver metastases (SSR-positive) in comparison with controls. No significant antitumor effect was seen in PRRT-treated rats with CC531 liver metastases (SSR-negative). Also, a dose-dependent tumor response was seen in rats with CC2B liver metastases treated with 185 MBq [ 177Lu-DOTA0, Tyr3 ]octreotate compared with controls. In addition, rats with mixed liver metastases treated with 185 MBq [177 Lu-DOTA0, Tyr3 ]octreotate had significantly fewer metastases compared with controls. CONCLUSIONS: The authors showed an impressive antitumor effect of SSR (subtype 2)-transfected colon carcinoma cells with PRRT in a rat liver metastasis model. Moreover, rats with mixed liver metastases had significantly fewer liver metastases compared with control rats, which may be due to a radiologic bystander effect of [177 Lu-DOTA0, Tyr3 ]octreotate. This phenomenon is beneficial in the concept of in vivo gene therapy.

No functional benefit for hDAF-transgenic rat livers despite protection from tissue damage following perfusion with human serum.

Currently, xenogeneic extracorporeal liver perfusion is used in the treatment of acute liver failure. In order to determine whether transgeneity for human regulatory proteins could improve the functional outcome of the ex-vivo liver in relation to the histopathological changes, we studied the effect of the humoral mechanism in xenogeneic isolated rat liver perfusion in normal and transgenic rat livers. Isolated rat liver perfusion was performed for 2 h in normal rat livers with Krebs Henseleit (KH) and human serum (HS), and in livers transgenic for human decay accelerating factor (hDAF; Tg HS). Function of the liver was established by measurement of liver enzymes and bile production, and clearance of bromosulphophthalein (BSP). Tissue specimens taken after perfusion were analysed by routine histology and immunofluorescence staining for C3c deposition. No change in release of liver enzymes could be established throughout the perfusion period. In the 2nd hour, a higher level of bile production was seen for the transgenic group than for the HS group. The transgenic rat livers outperformed the normal livers perfused with HS, when BSP concentration in the bile was measured; however, clearance of BSP from the perfusate was not significantly different. Haematoxylin-eosin (HE) staining of the liver tissue showed evidence of hyperacute rejection in the HS group. There was only mild tissue injury in the transgenic liver. High-intensity fluorescent staining for C3c deposition was seen in the normal livers perfused with HS, and significantly less in the transgenic livers. Although histologically less tissue damage and less C3c deposition was shown, no significantly improved function of the livers transgenic for hDAF was established. These results suggest that for short-term extracorporeal liver perfusion transgenesis offers no functional benefit.

Human decay-accelerating factor expressed on rat hearts inhibits leukocyte adhesion.

In xenotransplantation the use of donors transgenic for recipient-type complement regulatory protein decay-accelerating factor (DAF/CD55) or membrane co-factor protein (MCP/CD46) protects grafts against hyperacute rejection (HAR), which is primarily mediated by xenoreactive natural antibodies and complement. In the Langendorff model, we previously demonstrated that rat hearts transgenic for human CD55 (hCD55), perfused with human serum, were protected against HAR. However, ex vivo, these hearts were found to be destroyed by a process occurring after the period of HAR. The question arose as to whether hearts transgenic for hCD55 are also protected against adhesion and infiltration by cells implicated in the early phases of xenograft rejection. The aim of the present study was to analyze this process in the ex vivo heart perfusion model. hCD55-transgenic rat hearts and their controls were perfused with either heat-inactivated or normal human blood solutions for 60 min. Although most of the hearts had stopped beating within the 60-min perfusion period, the perfusion was not stopped to enable adhesion of cells during a fixed period identical for all groups. Independent of the presence of complement, H&E-stained tissues of hCD55-transgenic hearts revealed fewer PMN leukocytes adhering to the endothelium than the controls (mean: 31% vs 60%). Standard histology and immunohistochemistry showed that hCD55-transgenic hearts exhibited less interstitial edema, hemorrhage, microthrombosis, fibrin deposition, and leukocyte infiltration than did the controls. All hearts showed mild to moderate levels of P-selectin and similar levels of ICAM-1, C3c, C9, IgA, IgG, and IgM deposition. hCD55 expressed on rat hearts not only inhibits complement activation, but also human leukocyte adhesion and apparently functions as an anti-adhesion molecule. hCD55 is an efficient factor in protecting grafts against HAR and protects the graft against adhesion of leukocytes as well.

Prevention of adhesion to prosthetic mesh: comparison of different barriers using an incisional hernia model.

OBJECTIVE: To assess whether use of antiadhesive liquids or coatings could prevent adhesion formation to prosthetic mesh. SUMMARY BACKGROUND DATA: Incisional hernia repair frequently involves the use of prosthetic mesh. However, concern exists about development of adhesions between viscera and the mesh, predisposing to intestinal obstruction or enterocutaneous fistulas. METHODS: In 91 rats, a defect in the muscular abdominal wall was created, and mesh was fixed intraperitoneally to cover the defect. Rats were divided in five groups: polypropylene mesh only (control group), addition of Sepracoat or Icodextrin solution to polypropylene mesh, Sepramesh (polypropylene mesh with Seprafilm coating), and Parietex composite mesh (polyester mesh with collagen coating). Seven and 30 days postoperatively, adhesions were assessed and wound healing was studied by microscopy. RESULTS: Intraperitoneal placement of polypropylene mesh was followed by bowel adhesions to the mesh in 50% of the cases. A mean of 74% of the mesh surface was covered by adhesions after 7 days, and 48% after 30 days. Administration of Sepracoat or Icodextrin solution had no influence on adhesion formation. Coated meshes (Sepramesh and Parietex composite mesh) had no bowel adhesions. Sepramesh was associated with a significant reduction of the mesh surface covered by adhesions after 7 and 30 days. Infection was more prevalent with Parietex composite mesh, with concurrent increased mesh surface covered by adhesions after 30 days (78%). CONCLUSIONS: Sepramesh significantly reduced mesh surface covered by adhesions and prevented bowel adhesion to the mesh. Parietex composite mesh prevented bowel adhesions as well but increased infection rates in the current model.

Long-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient rats.

OBJECTIVE: To investigate the long-term impact of pneumoperitoneum used for laparoscopic donor nephrectomy on renal function and histomorphology in donor and recipient. SUMMARY BACKGROUND DATA: Laparoscopic donor nephrectomy has the potential to increase the number of living kidney donations by reducing donor morbidity. However, function of laparoscopically procured kidneys might be at risk due to ischemia as a consequence of elevated intra-abdominal pressure during laparoscopy. METHODS: In experiment 1, 30 Brown Norway rats were randomized to three procedures: 2 hours of CO2 insufflation, 2 hours of helium insufflation, and 2 hours of gasless laparoscopy. After this, a unilateral nephrectomy was performed in all animals. Another six rats were used as controls. In experiment 2, 36 donor Brown Norway rats were subjected to a similar insufflation protocol, but after nephrectomy a syngeneic renal transplantation was performed. All rats had a follow-up period of 12 months. Urine and blood samples were collected each month for determination of renal function. After 1 year, donor and recipient kidneys were removed for histomorphologic and immunohistochemical analysis. RESULTS: In donors as well as in recipients, no significant changes in serum creatinine, proteinuria, or glomerular filtration rate were detected between the CO2, the helium, and the gasless control group after 1 year. No histologic abnormalities due to abdominal gas insufflation were found. Immunohistochemical analysis did not show significant differences in the number of infiltrating cells (CD4, CD8, ED1, OX62, and OX6) and adhesion molecule expression (ICAM-1) between the three groups. CONCLUSIONS: Abdominal gas insufflation does not impair renal function in the donor 1 year after LDN. One year after transplantation, no differences in renal function or histomorphology were detected between kidney grafts exposed to either pneumoperitoneum or a gasless procedure.