Clinical consequence of vessel perforations during endovascular treatment of acute ischemic stroke.

PURPOSE: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. METHODS: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). RESULTS: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2-3.2)) and distal occlusion locations (aOR 2.2  (95% CI 1.3-3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23-0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. CONCLUSION: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk.

Follow-up infarct volume as a mediator of endovascular treatment effect on functional outcome in ischaemic stroke.

OBJECTIVE: The putative mechanism for the favourable effect of endovascular treatment (EVT) on functional outcome after acute ischaemic stroke is preventing follow-up infarct volume (FIV) progression. We aimed to assess to what extent difference in FIV explains the effect of EVT on functional outcome in a randomised trial of EVT versus no EVT (MR CLEAN). METHODS: FIV was assessed on non-contrast CT scan 5-7 days after stroke. Functional outcome was the score on the modified Rankin Scale at 3 months. We tested the causal pathway from intervention, via FIV to functional outcome with a mediation model, using linear and ordinal regression, adjusted for relevant baseline covariates, including stroke severity. Explained effect was assessed by taking the ratio of the log odds ratios of treatment with and without adjustment for FIV. RESULTS: Of the 500 patients included in MR CLEAN, 60 died and four patients underwent hemicraniectomy before FIV was assessed, leaving 436 patients for analysis. Patients in the intervention group had better functional outcomes (adjusted common odds ratio (acOR) 2.30 (95% CI 1.62-3.26) than controls and smaller FIV (median 53 vs. 81 ml) (difference 28 ml; 95% CI 13-41). Smaller FIV was associated with better outcome (acOR per 10 ml 0.60, 95% CI 0.52-0.68). After adjustment for FIV the effect of intervention on functional outcome decreased but remained substantial (acOR 2.05, 95% CI 1.44-2.91). This implies that preventing FIV progression explains 14% (95% CI 0-34) of the beneficial effect of EVT on outcome. CONCLUSION: The effect of EVT on FIV explains only part of the treatment effect on functional outcome. KEY POINTS: • Endovascular treatment in acute ischaemic stroke patients prevents progression of follow-up infarct volume on non-contrast CT at 5-7 days. • Follow-up infarct volume was related to functional outcome, but only explained a modest part of the effect of intervention on functional outcome. • A large proportion of treatment effect on functional outcome remains unexplained, suggesting FIV alone cannot be used as an early surrogate imaging marker of functional outcome.

Relabelling behaviour. The effects of psycho-education on the perceived severity and causes of challenging behaviour in people with profound intellectual and multiple disabilities.

BACKGROUND: Prevalence rates of challenging behaviour are high in children and adults with profound intellectual and multiple disabilities (PIMD). Moreover, many of these behaviours are observed daily. Direct support staff report that most challenging behaviour identified has little impact on the person with PIMD and attribute challenging behaviour in children and adults with PIMD mainly to a biomedical model. The purpose of this study was to evaluate whether an intervention (psycho-education) had any effect on direct support staff's assessment of challenging behaviour in terms of its severity and their biomedical causal explanations (attributions) for this behaviour. METHOD: A stepped wedge study design was used to evaluate the effects of a psycho-education intervention on the perceived severity and the attributions offered for challenging behaviour of people with PIMD by 198 direct support staff. We used questionnaires assessing the perceived severity of challenging behaviour and staff views of its causes. Data on the dependent variables were collected at four 1-month intervals. RESULTS: The intervention was found to have an effect on the perceived severity of challenging behaviour identified in people with PIMD in the sense that staff generally scored challenging behaviour as more severe in its consequences after the intervention. However, this effect was very small. No significant effects were found in terms of reduction in the biomedical scale scores. CONCLUSION: No evidence for the effectiveness of a psycho-educational approach on the assessment of challenging behaviour in terms of severity and the biomedical attributions for behaviour was found. More research is required to explore further the effects of more elaborate training using methods to enable direct support staff to reflect on the behaviour of people with PIMD and on their own behaviour.

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients. METHODS: The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics. DISCUSSION: The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05680389. Registered on January 11, 2023.

Initial Experience with the Solitaire X 3 mm Stent Retriever for the Treatment of Distal Medium Vessel Occlusions.

Endovascular therapy (EVT) is the standard treatment for ischemic stroke caused by a large vessel occlusion (LVO). The effectiveness of EVT for distal medium vessel occlusions (MDVOs) is still uncertain, but newer, smaller devices show potential for EVT in MDVOs. The new Solitaire X 3 mm device offers a treatment option for MDVOs. Our study encompassed consecutive cases of primary and secondary MDVOs treated with the Solitaire X 3 mm stent-retriever as first-line EVT device between January and December 2022 at 12 European stroke centers. The primary endpoint was a first-pass near-complete or complete reperfusion, defined as a modified treatment in cerebral infarction (mTICI) score of 2c/3. Additionally, we examined reperfusion results, National Institutes of Health Stroke Scale (NIHSS) scores at 24 h and discharge, device malfunctions, complications and procedural technical parameters. Sixty-eight patients (38 women, mean age 72 ± 14 years) were included in our study. Median NIHSS at admission was 11 (IQR 6-16). In 53 (78%) cases, a primary combined approach was used as the frontline technique. Among all enrolled patients, first-pass mTICI 2c/3 was achieved in 22 (32%) and final mTICI 2c/3 in 46 (67.6%) patients after a median of 1.5 (IQR 1-2) passes. Final reperfusion mTICI 2b/3 was observed in 89.7% of our cases. We observed no device malfunctions. Median NIHSS at discharge was 2 (IQR 0-4), and no symptomatic intracranial hemorrhages were reported. Based on our analysis, the utilization of the Solitaire X 3 mm device appears to be both effective and safe for performing EVT in cases of MDVO stroke.

Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke.

Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Carotid and basilar artery wall shear stress in Alzheimer's disease and mild cognitive impairment.

BACKGROUND/AIMS: Vascular pathology is increasingly seen as a factor contributing to the development of Alzheimer's disease (AD). With this in mind we hypothesized that this vascular pathology could be directly detected in the arteries contributing to the cerebral circulation of mild cognitive impairment (MCI) and AD patients by means of wall shear stress (WSS) measurements. METHODS: In this study we investigated the mean wall shear stress (MWSS), diastolic wall shear stress (DWSS) and systolic wall shear stress (SWSS) in the carotid and basilar arteries of control subjects (mean age: 72; SD: 8.8), patients suffering from MCI (mean age: 76; SD: 6.7), and patients suffering from AD (mean age: 72; SD: 8.2) that were consecutively referred to our outpatient memory clinic using in-house developed software on gradient echo phase-contrast MRI sequences. RESULTS: We found that all these parameters were significantly lower in the carotid arteries of patients suffering from AD or MCI when compared to control subjects. In the basilar artery only DWSS was lower in MCI or AD patients compared to control subjects. In none of the arteries a difference was found for any WSS parameter between MCI and AD patients. WSS parameters were significantly associated (corrected for age and sex) with the degree of cognitive impairment. CONCLUSION: Increased vascular pathology, as expressed by lower WSS measures, was found in patients suffering from MCI and AD compared to normal controls. This might point to the involvement of vascular pathology in the development of AD.

Flow Patterns in Carotid Webs: A Patient-Based Computational Fluid Dynamics Study.

BACKGROUND AND PURPOSE: Carotid webs are increasingly recognized as an important cause of (recurrent) ischemic stroke in patients without other cardiovascular risk factors. Hemodynamic flow patterns induced by these lesions might be associated with thrombus formation. The aim of our study was to evaluate flow patterns of carotid webs using computational fluid dynamics. MATERIALS AND METHODS: Patients with a carotid web in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) were selected for hemodynamic evaluation with computational fluid dynamics models based on lumen segmentations obtained from CT angiography scans. Hemodynamic parameters, including the area of recirculation zone, time-averaged wall shear stress, transverse wall shear stress, and the oscillatory shear index, were assessed and compared with the contralateral carotid bifurcation. RESULTS: In our study, 9 patients were evaluated. Distal to the carotid webs, recirculation zones were significantly larger compared with the contralateral bifurcation (63 versus 43 mm2, P = .02). In the recirculation zones of the carotid webs and the contralateral carotid bifurcation, time-averaged wall shear stress values were comparable (both: median, 0.27 Pa; P = .30), while transverse wall shear stress and oscillatory shear index values were significantly higher in the recirculation zone of carotid webs (median, 0.25 versus 0.21 Pa; P = .02 and 0.39 versus 0.30 Pa; P = .04). At the minimal lumen area, simulations showed a significantly higher time-averaged wall shear stress in the web compared with the contralateral bifurcation (median, 0.58 versus 0.45 Pa; P = .01). CONCLUSIONS: Carotid webs are associated with increased recirculation zones and regional increased wall shear stress metrics that are associated with disturbed flow. These findings suggest that a carotid web might stimulate thrombus formation, which increases the risk of acute ischemic stroke.

Lobar distribution of changes in gray matter and white matter in memory clinic patients: detected using magnetization transfer imaging.

BACKGROUND AND PURPOSE: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline. MATERIALS AND METHODS: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage. RESULTS: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition. CONCLUSION: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.

Measuring longitudinal white matter changes: comparison of a visual rating scale with a volumetric measurement.

BACKGROUND AND PURPOSE: Detection of longitudinal changes in white matter hyperintensities (WMH) by using visual rating scales is problematic. We compared a widely used visual rating scale with a volumetric method to study longitudinal white matter changes. METHODS: WMH were assessed with the visual Scheltens scale and a volumetric method in 100 elderly subjects aged 70-81 years for whom repetitive MR images were available with an interval of 33 (SD, 1.4) months. Reliability was determined by intraclass correlation coefficients. To examine the sensitivity of both the visual and volumetric method, we calculated Spearman rank correlations of WMH ratings and volume measurements with age. RESULTS: Reliability of the visual rating scale was good, whereas reliability of the volumetric measurement was excellent. For baseline measurements of WMH, we found weaker associations between WMH and age when assessed with the visual scale (r = 0.20, P = .045) than with the volumetric method (r = 0.31, P = .002). Longitudinal evaluation of WMH assessments showed regression in 26% of the subjects when analyzed with the visual rating scale against 12% of the subjects when using volumetric measurements. Compared with the visual rating, the correlation between progression in WMH and age was twice as high when using the volumetric measurement (r = 0.19, P = .062 and r = 0.39, P < .001, respectively). CONCLUSION: Volumetric measurements of WMH offer a more reliable, sensitive, and objective alternative to visual rating scales in studying longitudinal white matter changes.

Energy requirements and energy expenditure of lean and overweight women, measured by indirect calorimetry.

To estimate the energy requirement of lean and overweight women, 29 lean (body weight, 59 +/- 1 kg; means +/- SEM) and 18 overweight (94 +/- 5 kg) women consumed a weight-maintenance diet for 8 d. The final 80 h were spent in a whole-body indirect calorimeter. Actual metabolizable energy intake (ME) was measured by analyzing food, feces, and urine. Mean ME was 8.88 +/- 0.13 MJ/d (2123 +/- 30 kcal/d) (lean) and 10.12 +/- 0.29 MJ/d (2419 +/- 70 kcal/d) (overweight). Mean 24-h energy expenditure (24hEE) of the lean (8.58 +/- 0.13 MJ or 2052 +/- 32 kcal) was lower than that of the overweight (10.70 +/- 0.45 MJ or 2558 +/- 108 kcal; p less than 0.001) women. Energy balance was close to zero in both groups. Therefore, 24hEE was used as an estimation of energy requirement. Multiple-regression analysis showed body weight to be the best single predictor of 24hEE. Our data may be useful for prediction of energy requirements of women (aged 20-50 yr) in normal life.

Energy metabolism of overweight women 1 mo and 1 y after an 8-wk slimming period.

Twenty-four hour energy expenditure (24EE) and spontaneous physical activity were measured in 13 overweight women before and at the end of an 8-wk slimming period. These measurements were repeated in 10 women 1 mo after the slimming period (1-mo follow-up) and in eight women 1 y after slimming (1-y follow-up). The weight loss achieved after 8 wk of slimming (8.7-9.9 kg) was maintained throughout the follow-up periods; 24EE decreased during slimming from 9572 +/- 703 (means +/- SD) to 8060 +/- 471 kJ/d and increased after refeeding to 8379 +/- 739 kJ/d after 1 mo and to 8285 +/- 454 kJ/d after 1 y. On the basis of body weight, energy requirement (approximately 126 kJ.kg-1.d-1) did not change throughout the slimming and follow-up programs. Spontaneous physical activity, which had been lowered during slimming, tended to increase afterwards. No changes in metabolic efficiency seemed to occur or persist.

Adaptation of energy metabolism of overweight women to low-energy intake, studied with whole-body calorimeters.

In 14 overweight women, 24-h energy expenditure (EE) was measured in a whole-body indirect calorimeter: before weight reduction (100% diet), after 1 wk on a 4.2-MJ diet, after 8 wk on 4.2-MJ diet, after weight reduction on 100% diet. Data of two subjects were excluded. Mean body weight declined from 93.3 +/- 7.4 (mean +/- SD) to 83.4 +/- 7.7 kg; 24-hEE decreased from 10.52 +/- 0.83 MJ on the 100% diet to 9.58 +/- 0.75 MJ on the 4.2-MJ diet. After 8 wk, 24-hEE had decreased by 15% of the initial 24-hEE to 8.92 +/- 0.65 MJ. After refeeding (1 wk), it increased to 9.45 +/- 0.75 MJ. Calculated energy requirement before weight reduction was 10.62 +/- 0.88 MJ/day; after weight reduction, 9.39 +/- 0.79 MJ/day. The decrease was more than that predicted from the change in body weight and body composition. An adaptation probably occurs, which may be metabolic.

Adaptation of energy metabolism of overweight women to alternating and continuous low energy intake.

To investigate whether a slimming diet based on alternating (low with normal) energy intakes could counteract a decrease in energy requirement, 24-h energy expenditure (24EE), sleeping energy expenditure (sleeping EE), and physical activity were determined in a respiration chamber in 27 overweight women: before weight reduction and after 4 and 8 wk of slimming. Daily alternating and continuous slimming diets were supplied. Average weight losses over 8 wk of slimming were 6.9-9.0 kg. After 8 wk at low energy intake, 24EE had declined by 12-16% (from 2328 +/- 219 to 1987 +/- 204 kcal, mean +/- SD). Sleeping EE had declined by 7-13% (from 64 +/- 6 to 57 +/- 6 kcal/h). Measurements of physical activity indicated a reduction of spontaneous physical activity during slimming. Alternating low energy intake did not prevent 24EE from declining. The reduction in 24EE was determined by a decrease of body weight, dietary induced thermogenesis (in proportion to caloric restriction), and physical activity. There seems little reason to consider other adaptive mechanisms.

Influence of blood transfusions and matching for DR antigens on kidney allograft survival in unrelated rhesus monkeys.

Kidney transplantations were performed in unrelated, immunosuppressed rhesus monkeys matched for two DR antigens and given five pretransplant transfusion of whole blood. The host-donor combinations were either reactive or nonreactive in mixed lymphocyte culture (MLC) and shared up to three A and B locus antigens with their blood and kidney donors. Although previous monkey experiments had shown a definite positive influence of DR matching as well as of pretransplant transfusions on graft survival, this was not found in the current experiments (the mean survival time for the MLC responsive group was 21.3 days for the MLC nonresponsive group 28.2 days). It appears therefore that the combination of pretransplant transfusions and matching for DR antigens does not have an additive or synergistic effect on graft survival. In fact, the prominent transfusion effect demonstrated previously may have been somehow compromised by matching for DR antigens. Alternatively, the clearly positive effect of matching for two DR antigens may have been reduced or lost as a consequence of giving the blood transfusions.

Serological matching for D locus antigens improves kidney allograft survival in rhesus monkeys.

A prospective study performed in unrelated, unimmunized rhesus monkeys revealed that serological matching for D-associated Ia1 antigens improves kidney allograft prognosis, provided that the recipients are nonreactive in mixed lymphocyte cultures (MLC) against their donors. MLC-negative host-donor combinations showed a more than 3-fold increase in the mean survival time as compared with MLC-positive combinations. Apparently, compatibility for the most important MLC-stimulating determinants is required for a significant improvement in graft survival. On the other hand, matching for A and B loci antigens did not play a decisive role. Since the relatively simple matching on the basis of identity for Ia1 (or DR) antigens yields a rather high proportion of MLC-nonreactive combinations, this method is likely to become an essential addition to the conventional matching procedures, also in clinical organ transplantation.

Prolongation of heterotropic heart allograft survival in rats by use of antigen-antibody complexes.

Treatment of BN recipients with soluble WAG/Rij histocompatibility antigens (HCA) did not produce prolongation of (WAG/Rij X BN) F1 heart allografts but resulted in specific sensitization of the recipients in most cases. Three different anti-WAG/Rij sera (ADS) were tested, either alone or complexed in equivalence to 0.5 mg of HCA. Depending on the serum used, ADS alone produced only a moderate prolongation of heart allograft survival or had no effect at all. Antigen-antibody complexes given i.v. on days 0, 2, 4, 6, and 8 induced a prolonged or indefinite cardiac graft survival (greater than 200 days), as well as accelerated graft rejection, depending on the source of the ADS used in immune complex formation. One month after heart transplantation, BN recipients, treated with antigen-antibody complexes, demonstrated normal graft-versus-host reactivity of peripheral blood lymphocytes, but rejected donor-type skin grafts in a slightly delayed fashion.

Influence of a single blood transfusion on kidney allograft survival in unrelated rhesus monkeys.

A prospective study was performed in moderately immunosuppressed unrelated rhesus monkeys to investigate the influence of a single transfusion on kidney allograft survival. The recipients received either whole citrated blood or plasma-free transfusates consisting of pure red blood cell or lymphocyte suspensions. Except for one group, in which blood and kidney donors were optimally matched, transfusions and kidney allografts were disparate for two to four A/B locus antigens with the recipients. Transfusions were given 2 to 4 weeks before kidney grafting, except in one experimental group where the recipients were transfused 0 to 12 hr before transplantation. The general trend was that graft prolongation could be obtained with all experimental protocols. However, it was also shown that a single transfusion entails the risk of accelerated rejection. This adverse effect was not observed in the animals receiving blood and kidneys from donors optimally matched for A/B locus antigens and in recipients transfused shortly before or during transplantation. These results may contribute to a further improvement of the current clinical transfusion policy.

Attempts to induce immunological enhancement for kidney allografts in rhesus monkeys.

Various rhesus alloantisera were tested for their capacity to induce enhancement of kidney allograft survival in D locus-incompatible rhesus monkeys. Six experimental groups were investigated: 1, ten allografted monkeys remained untreated; 2, six recipients were treated with Imuran and prednisolone; 3, eight rhesus monkeys were treated with a polyspecific "anti-SD" serum; 4, four animals were given oligospecific antikidney serum; 5, four monkeys were treated with oligospecific antiblood serum; and 6, nine recipients were given anti-Ia-like sera plus immunosuppressive treatment with Imuran and prednisolone. It was found that neither treatment with Imuran and prednisolone nor the administration of any of the alloantisera had a substantial effect on kidney graft survival. However, there appeared to be a difference in renal function among experimental groups. At 6 days after grafting, the mean blood urea level in the group treated with Ia-like antisera was found to be significantly lower than those of all other groups. It is discussed that this favourable effect is attributable to treatment with anti-Ia-like sera and not to the additional factors (conventional immunosuppression and partial matching for Ia-like antigens) occurring in this experimental group.