Cyclosporin A-induced tolerance is not amplified by the addition of a steroid therapy

Abstract. The effect of adding steroids to a cyclosporin A (CyA) schedule designed to induce tolerance to heart allografts in rats was investigated. CyA treatment alone, at a dose of 15 mg/kg per day for 2 weeks, resulted in the successful induction of tolerance (graft survival > 100 days) in 70% of the rats. The inclusion of 5 mg/kg of steroids (Solumedrone), administered IM for 40 or 60 days, not only failed to improve this long-term survival (LTS) rate achieved with CyA alone but reduced it from 70% to 50% after 40 days ofsteroid treatment and to 30% after 60 days of steroid treatment. The administration of 5 mg/kg and 40 mg/kg of steroids during the "high-risk" period for graft rejection (days 30–50 or 40–60) was shown to delay but not prevent subsequent rejections from occurring. Steroid treatment alone (5 mg/kg per day) was found to be only weakly immunosuppressive. Thus, we have demonstrated that the addition of steroids to a CyA tolerizing schedule was detrimental to the induction of tolerance.     

The induction of operational tolerance is not prevented by simultaneous administration of cyclosporin A1

In this study, the effect of combining anti-CD4 monoclonal antibody (mAb) and cyclosporin (CyA) therapy at the time of transplantation was examined. A mouse cardiac allograft model was used. Anti-CD4 mAb administered perioperatively induces long-term survival. The addition of a short course of CyA given subcutaneously in a regimen of either a high-dose treatment or a standard dose treatment to the anti-CD4 mAb treatment protocol did not have a detrimental effect on graft survival. Despite having no significant effect on graft survival, the addition of CyA to the treatment protocol did result in a significant decrease in the level of IL-2 present in the hearts 7 days after transplantation. The decrease in IL-2 production was directly related to the presence of CyA in vivo. When CyA treatment was continued throughout the period during which unresponsiveness to the graft is induced by anti-CD4 mAb therapy, 50 % of the grafted hearts were rejected once the CyA was discontinued. In conclusion, the combined use of anti-CD4 mAb therapy and CyA did not have a negative effect on graft survival in this model when the two agents were used concurrently at the time of transplantation. Received: 2 October 1996 Received after revision: 31 January 1997 Accepted: 5 February 1997     

Restoration of tolerance to rat hepatic allografts by spleen-derived passenger leukocytes

The tolerance induced by orthotopic liver transplantation (OLT) in certain combinations of rat strains can be prevented by total body irradiation (TBI) of the donor. We demonstrate here that the intravenous inoculation of splenic leukocytes into irradiated donors before OLT could re-establish tolerance in association with a state of microchimerism detected in the recipients. When donor DA (RT1^a) strain rats were irradiated with 1000 rad 24 h before liver harvesting and subsequent liver implantation into PVG recipients, five out of six rats died from rejection in this normally tolerogenic OLT (DA-PVG) combination. Injection of 1.5x10⁸ splenic leukocytes from naive DA rats into the irradiated DA donor rats 24 h before OLT restored the tolerogenic potential of the liver allografts. Immunofluorescence assay revealed an increased number of donor (DA) type cells in the PVG recipient bearing a repopulated DA liver, compared to the PVG recipient of an irradiated liver. These results suggest that passenger leukocytes reconstituted by splenic leukocytes have the capacity to protect liver allografts.     

An unusual cause of paraparesis in a patient on chronic steroid therapy

BACKGROUND/OBJECTIVE: Spinal epidural lipomatosis is the excessive deposition of unencapsulated fat in the epidural space. This is a rare disorder often associated with high levels of endogenous steroids or the administration of exogenous steroids. CASE DESCRIPTION: A 32-year-old man with congenital kyphosis treated with prednisolone daily for 5 months for interstitial lung disease developed compressive myelopathy. FINDINGS: Magnetic resonance imaging showed congenital kyphosis along with epidural lipomatosis compressing the cord. Cessation of steroid therapy was associated with improvement in the symptoms. CONCLUSIONS: Spinal epidural lipomatosis is a rare side effect of chronic steroid therapy that may occur with relatively short-term, low-dose regimens. In patients with congenital vertebral anomalies, spinal fat deposition may worsen the neurological status in an already compromised cord. Discontinuation of steroid therapy is beneficial; some patients may require surgical intervention for decompression.     

Applicability of steroid therapy in 275 adult patients with IgA nephropathy determined using a histological scoring system and degree of proteinuria

Background The purpose of this study was to propose clinical and pathologic criteria for the indication for steroid therapy (ST) in adult IgA nephropathy (IgAN).Methods We analyzed 275 adult IgAN patients retrospectively, using a histological scoring system. The histological score was expressed by evaluating, semiquantitatively, the extent of glomerular and tubulointerstitial lesions in terms of the activity index (AI) and chronicity index (CI). To determine the applicability of ST, three groups were categorized by evaluating the statistical significance of the correlation between the AI and CI, together with the daily amount of urinary protein (UP) and the outcome.Results In group A, which had a CI 5 alone, 33 out of 43 patients showed a decline in renal function. There was no statistically significant difference between the subgroup with ST and that without ST. In group B, which had CI < 5, AI < 5, and UP < 1.0g/day, 169 out of 174 patients had normal renal function irrespective of whether or not they received ST. Thus, ST had no beneficial effects in group A and B patients. In group C, which had CI < 5 and AI 5 or UP 1.0g/day, patients with ST had a significantly higher incidence of an outcome with normal renal function (22 out of 24 patients) than that in patients without ST (19 out of 34 patients) (P < 0.01). Thus, ST had beneficial effects in group C patients.Conclusions We propose that a histological criterion be used in combination with the degree of proteinuria as an indication for ST in adult IgAN patients.     

DA与Lewis大鼠品系组合建立大鼠肝移植排斥与耐受模型

目的 建立大鼠原位肝脏移植急性排斥与自然耐受模型.方法 采用近交系雄性DA大鼠与Lewis大鼠互为供受体,改良"二袖套"法建立大鼠原位肝脏移植(rat orthotopic liver trans-plantation,ROLT)模型84例.实验分为4组:排斥组(DA→Lewis,n=12),FK506处理排斥组[DA→Lewis,n=24,术后1～7 d用FK506 0.2 mg/(kg·d)灌胃],耐受组(Lewis→DA,n=24),同基因组(DA→DA,n=24).各组中随机取6例观察生存期,其余分别于术后7、14、28 d处死6例,收集外周血及肝脏标本.检测血清标本天冬氨酸转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)浓度,病理学检查移植物排斥反应程度.结果 排斥组中位生存时间(median surviv-al time,MST)为12 d,而FK506处理排斥组MST为76 d,较排斥组明显延长(vs排斥组,P<0.01).耐受组与同基因组的MST均>120 d.术后7 d,排斥组血清AST、BILI浓度均明显高于其余3组(P<0.05);术后14 d,FK506处理组、耐受组和同基因组血清AST、TBIL浓度无明显差异.术后28 d,FK506处理组血清AST、TBIL浓度较耐受组和同基因组明显升高(P相似文献   

Clinical significance of histological grading and staging for predicting the effectiveness of steroid therapy in IgA nephropathy

Background. A beneficial effect of steroid therapy for IgA nephropathy (IgAN) has been reported. However, precise histological criteria for steroid therapy have not yet been established. The present study was designed to assess the clinical validity of histological grading and staging for predicting the responsiveness to steroid therapy in IgAN. Methods. We performed a retrospective study of 27 patients with IgAN who underwent steroid therapy. The duration of steroid therapy was 42.9 ± 23.1 months, and the mean follow-up period was 7.5 ± 2.4 years, ranging from 4 to 14 years. Responsiveness to the steroid therapy was evaluated by reduction of urinary protein at 1 year after treatment; more than 50% reduction of initial urinary protein and less than 1.0 g/day. Responsiveness to the therapy was also evaluated by preservation of renal function; i.e., maintenance of serum creatinine level under 2.0 mg/dl during follow-up. The histological grading and staging method (G-S system) proposed by Shigematsu was used to evaluate the histological severity of lesions in renal biopsy specimens. Univariate analyses of clinical and histological parameters, using the logistic regression model or Cox proportional hazards model, were performed to find predictive factors for the effectiveness of steroid therapy. Results. No clinical parameters at the start of treatment predicted the effectiveness of the steroid therapy. However, some histological parameters – crescent formation rate (%), grade of glomerular extracapillary lesions (Gex) and grades of acute and chronic interstitial inflammation (Gint and Sint) – were predictive for the effectiveness of steroid therapy. To predict reduction of proteinuria at 1 year after steroid therapy, the crescent formation rate, Gex, Gint, and Sint were significant (odds ratio; P value): crescent formation rate per 10% increment (2.91; P = 0.019), Gex per 0.1 grade increment (1.56; P = 0.021), Gint per one grade increment (0.20; P = 0.022), and Sint per one grade increment (0.33; P = 0.039). These results indicated that a high crescent formation rate and active extracapillary lesions predicted favorable response, and active and chronic interstitial lesions predicted lower efficacy in proteinuria reduction. To predict deterioration of renal function, Gint and Sint were significant (hazard ratio; P value): Gint per one grade increment (3.30; P = 0.015) and Sint per one grade increment (2.99; P = 0.006), indicating that high degrees of acute and chronic interstitial inflammation predicted the deterioration of renal function. Conclusions. The severity of acute glomerular extracapillary lesions predicts the possibility of reduction in proteinuria after steroid therapy, while the severity of interstitial inflammation suggests a lower efficacy for proteinuria reduction and a high risk of renal dysfunction even after steroid therapy in IgAN. Received: August 17, 1999 / Accepted: May 8, 2000     

Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression

BACKGROUND: After renal transplantation immunosuppressive drugs-like cyclosporin A (CsA) and FK506 induce either hypoaldosteronism or pseudo-hypoaldosteronism presenting with hyperkalemia and metabolic acidosis. We investigated the relationship between renal allograft function under CsA therapy and plasma aldosterone concentration, potassium- and water homeostasis and mineralocorticoid receptor (MR) expression level in peripheral leukocytes. METHODS: We studied 21 renal transplant patients under CsA therapy and 12 healthy controls. Transplant recipients were studied before and under fludrocortisone treatment. Using quantitative reverse-phase polymerase chain reaction (RT-PCR) specific for the MR, we analyzed the level of expression of MR in peripheral leukocytes. RESULTS: In acidotic transplant recipients (HCO(3) 18.5 +/- 1.2 mM) renal function was only slightly impaired with 2.0 +/- 0.2 mg creatinine/dL when compared with 1.8 +/- 0.3 mg/dL (ns) in non-acidotic patients (HCO(3) 23.0 +/- 2.8 mM). Mean plasma aldosterone levels in renal transplant recipients did not differ from control levels (150 +/- 33 pg/mL vs. 148 +/- 33 pg/mL, ns). In contrast, the expression level of MR in peripheral leukocytes of renal transplant recipients treated with CsA was significantly decreased when compared with healthy controls without renal disease (120 +/- 78 vs. 423 +/- 73 RNA molecules/0.5 microg total RNA, p < 0.01). The level of expression of MR in renal transplant recipients did not differ between acidotic patients and non-acidotic patients (ns). The application of fludrocortisone reversed hyperkalemia and metabolic acidosis without significant effect on MR expression. CONCLUSIONS: The present data demonstrate that hyperkalemia and metabolic acidosis following CsA treatment in kidney transplantation might be associated with a down-regulation of MR expression on peripheral leukocytes. Electrolyte imbalance is reversible on application of fludrocortisone. This observation supports fludrocortisone treatment in transplant patients with severe electrolyte disturbances.     

Enhancement of the immunosuppressive effect of cyclosporin A by ciprofloxacin in a rat cardiac allograft transplantation model

Ciprofloxacin hyperinduces interleukin-2 production in stimulated human and mouse lymphocytes. In this study, an enhanced and prolonged interleukin-2 response was also detected in polyclonally stimulated rat splenocytes in the presence of ciprofloxacin (5–80g/ml) compared to control cells without any antibiotic. Ciprofloxacin was able to counteract the immunosuppressive effect of 10ng/ml cyclosporin A (CyA) but did not interfere with higher CyA concentrations. In parallel, ciprofloxacin did not influence thymidine uptake in mixed lymphocyte reactions in the presence of CyA. To obtain an in vivo application of these findings, graft survival was studied by performing rat cardiac allograft transplantations in the presence or absence of CyA. Brown Norway rats served as donors and Wistar Furth rats as recipients. Ciprofloxacin was injected intraperitoneally either at a high-dose regimen (240 mg/kg per 24h) into rats every 8th h starting 1 day before transplantation until day 21 or graft loss, or it was injected at a low and clinically relevant dose regimen (45mg/kg per 24h) until day 9. CyA was administered orally (10mg/kg per 24h) from day 1 through day 9. Ciprofloxacin given alone at a high-dose regimen resulted in a median graft survival of 14.8 days, which was significantly longer than graft survival in rats without treatment (median 8.0 days). A low-dose regimen of ciprofloxacin alone did not affect graft survival. Ciprofloxacin at a highdose regimen combined with CyA prolonged graft survival to a median of 24.0 days compared to 20.5 days with CyA alone. Ciprofloxacin administered in the drinking water (200mg/kg per 24h) until day 9 in addition to CyA did not affect graft survival. However, when the same dose regimen was used in experiments with PVG rats as donors and Wistar/Kyoto as recipients, graft survival was significantly prolonged to a median of 45 days. Ciprofloxacin, given orally without the addition of CyA, did not influence graft survival in either of the two strain combinations. Thus, our data show that ciprofloxacin has no negative impact on heart graft survival rats. It remains to be clarified whether ciprofloxacin influences graft survival in humans.     

Clinicopathological study of IgA nephropathy in adults: The influence of onset age on clinical and renal histological findings and on the effect of steroid therapy

Background. The prognosis of IgA nephropathy (IgAN) varies according to the patient's age. It usually affects children or young adults. However, the onset age for IgAN may be at middle-age or older. The influence of onset age on the clinical and renal histological findings of adult IgAN was investigated. Methods. We selected 39 IgAN patients in whom renal biopsy was performed within 2 years from the onset. The patients were divided into two groups according to onset age; early-onset group (under 35 years; group E) and late-onset group (over 35 years; group L). The clinical and histological findings and the response to steroid therapy were compared in the two groups. Results. (1) Clinically, the levels of proteinuria and hematuria in groups E and L were not different, but the creatinine clearance was lower in group L than in group E. Hypertension was frequent in group L (66.7%), but not in group E. (2) Histologically, the rate of glomerular obsolescence and the grades of interstitial fibrosis and arterio- and arteriolosclerosis were more advanced in group L than in group E. However, there were no differences in the grade of mesangial cell proliferation or mesangial matrix increase, nor were the rates of glomerular crescent and tuft adhesion formation different between the two groups. (3) The reduction of proteinuria and hematuria after 1-year steroid therapy was similar in the two groups. Conclusion. Onset age does not affect the severity of glomerular lesions and the effect of steroid therapy in the early phase of adult IgAN. However, advanced interstitial fibrosis and arterio- and arteriolosclerosis, which may be related to hypertension or the aging process, lead to impaired renal function in late-onset IgAN patients. Received: March 18, 1998 / Accepted: October 29, 1998     

A requirement for continued graft presence in the maintenance of systemic tolerance induced by cyclosporin A (CyA) in rats

We report on a requirement for the continued presence of a heart graft in the maintenance of systemic tolerance induced by cyclosporin A (CyA). Hearts from DA rats (RT1a) were grafted into PVG (RT1c) recipient. CyA-induced long-term survivors (LTS) bearing functioning heart grafts are systemically tolerant, as demonstrated by the significant prolongation (>50 days) of donor-strain skin grafts. In contrast, donor-strain skins grafted 3 weeks after the removal of heart grafts from LTS are acutely rejected (median survival 10.0 days;P<0.005). Using an adoptive transfer assay, 5×10⁷ splenic lymphocytes obtained from LTS 3 weeks after the removal of the heart grafts fail to mediate adoptive tolerance (median survival 17.0 days), in contrast to the tolerance achieved by splenic lymphocytes obtained from LTS with functioning heart grafts (median survival >100 days;P<0.005).     

IL-4与IL-10联合诱导异种骨移植免疫耐受的实验研究

[目的]探讨IL-4和IL-10在诱导异种骨移植免疫耐受中的作用。[方法]取雄性BALB／c小鼠60只（体重20～22g）为骨移植受体，取新西兰兔1只为异种骨供体。实验用小鼠股后肌袋骨移植模型。将动物随机等分为A、B、C 3组，在小鼠左肢股后肌袋植入新鲜异种骨粒（75mg／只）并做如下处理。A组为对照组，腹腔注射生理盐水200 μl；B组腹腔注射IL-4和IL-10各0．5 μg（100 μl）；C组植骨部注射IL-4和IL-10各0．5 μg（100 μl）。于术后1、2、4、6周分批取材。通过检测受者的淋巴细胞刺激指数、细胞因子及组织学变化，观察诱导异种骨移植免疫耐受的效果。另取BALB／c小鼠10只和本地菜兔1只做二次移植实验，确定免疫抑制作用是否有供体特异性。[结果]与A组相比，B和C组注射IL-4及IL-10后均明显抑制了骨抗原二次刺激引起的细胞增殖（P〈0．01），腹腔注射起效早，局部注射作用持久。细胞因子检测，早期B组IL-2和IFN-γ分泌增加（P〈0．05），C组仅IFN-γ分泌增加；2周时两组的IFN-γ和IL-4分泌均明显减少（P〈0．05），C组的IL-2分泌也明显减少（P〈0．001）。组织学检查，注射IL-4和IL-10后植骨部炎细胞浸润少，尤其C组诱导成骨较多。二次移植实验表明，IL4和IL-10的免疫抑制作用有供体抗原特异性。[结论]IL-4和IL-10能有效抑制新鲜异种骨移植免疫反应，促进耐受形成。抑制作用在早期主要通过细胞因子调节，使Th1／Th2达到动态平衡而实现。腹腔注射起效早，局部注射作用持久。     

Demonstration of synergistic effects of hyperthermia and photodynamic therapy using the chick chorioallantoic membrane model.

The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.     

Successful management of hemolysis in ABO-nonidentical orthotopic liver transplantation by steroid therapy: a case report

Hemolysis due to donorderived B lymphocytes has been reported in patients who have undergone ABO-nonidentical orthotopic liver transplantation (OLT). Yet, until now, little was known about the management of this transplantation-induced hemolysis. In this report we describe our experience with hemolysis in a patient after OLT. In addition, based on theoretical assumption, we hypothesize that corticosteroids can be helpful in the management of ABO-nonidentical OLT-induced hemolysis.     

Immunosuppression in renal transplantation: Long-term clinical trial of a double versus triple therapy regimen

Summary: Sixty-nine renal allograft recipients were randomized to two immunosuppressive regimens: 35 patients received cyclosporine A and prednisolone (PC) while 34 patients received low dose cyclosporine A, prednisolone and short term azathioprine (PCA). the data of 66 patients (34 in PC and 32 in PCA groups) were analysed. the median follow-up periods were 62 months for the PC group and 60 months for the PCA group. There was no difference in graft survival between the two groups but five patients died in the PC group compared to none in the PCA group (graft survival: 88 vs 90% at 1 year and 82 vs 82% at 5 years, P = not significant at any time point; patient survival: 90 vs 100% at 1 year and 88 vs 100% at 5 years, P = 0.05 at 5 years). There was a trend for patients in the PCA group to develop earlier and more frequent rejections (not significant; P = 0.106 and P = 0.062, respectively). There were also more episodes of acute cyclosporine A nephrotoxicity and cytomegalovirus (CMV) infection in the PC group. the mean serum creatinine at 5 years was significantly higher in the PCA group when compared to the PC group (179.8 ± 76.5 μmol/L vs 154.7 ± 41.0 μmol/L; P =0.05). We found that both therapeutic regimens were effective in preventing renal allograft rejections. However, double therapy was associated with higher patient mortality secondary to infection. Patients on triple therapy, on the other hand, were more prone to develop rejections in the early post-transplant period and were associated with less favourable renal function in the long run.     

The use of parabiosis for investigating the mechanism of transplantation tolerance in bone marrow chimeras induced by total lymphoid irradiation

The mechanism of transplantation tolerance in total lymphoid irradiation (TLI)-induced semiallogeneic bone marrow chimeras without clinical evidence of graftversus-host disease (GVHD) was investigated using the technique of surgical parabiosis. When held in parabiosis with normal BALB/c mice, BALB/c (BALB/cxC57BL/6) F1 (BALBF1) chimeras survived 7–9 days, significantly (P<0.001) shorter than the 12–19 day survival of normal F1 hybrids kept in parabiosis with normal BALB, and in contrast to indefinite (>200 days) survival of syngeneic BALB parabiotic partners. When C57 skin grafts were placed on BALB mice held in parabiosis with BALBF1 chimeras, C57 skin grafts survived 50–60 days, in contrast to 10–14 days in normal BALB recipients (P<0.001). Lethal GVHD, induced in sublethally irradiated F1 recipients by 10⁷ BALB spleen cells, could not be delayed or prevented by cotransfer of 10⁷ to 30x10⁷ tolerant BALB spleen cells obtained from stable BALBF1 chimeras. GVHD reactivity of BALB spleen cells isolated from BALBF1 chimeras tolerant of C57 could not be recovered by depletion of Lyt 2 cytotoxic suppressor cells. Taken together, in the absence of suppressive capacity by suppressor cells, these data support functional clonal deletion as the primary mechanism responsible for the maintenance of unresponsiveness to host alloantigens in TLI-induced semiallogeneic chimeras, since no protection against induction of GVHD could be documented in vivo. The transfer of relative unresponsiveness to the host's alloantigens to the normal BALB partner of BALB/BALBF1 parabiotic pairs following sparation is also compatible with the latter conclusion, although transfer of suppressor cells capable of blocking rejection but not GVHD against the same alloantigens cannot yet be formally excluded.     

Photodynamic therapy for the treatment of vertebral metastases in a rat model of human breast carcinoma.

The feasibility and efficacy of photodynamic therapy (PDT) for the treatment of vertebral metastases using a minimally invasive surgical technique adapted from vertebroplasty was evaluated in a rodent model. Initial validation included photosensitizer (benzoporphyrin-derivative monoacid-ring A) drug uptake studies and in vitro confirmation of PDT efficacy. Intracardiac injection of human MT-1 breast cancer cells was performed in athymic rats. In 63 rats that developed vertebral metastases 21 days post-inoculation, single treatment of PDT was performed using a parapedicular approach placing an optical fiber adjacent to targeted vertebrae. Two milligrams per kilogram of photosensitizer drug was administered intravenously followed by 150 mW of 690 nm light illumination at varying drug-light intervals and light energies. Histologic and immunohistochemical analysis was performed assessing treatment effect. Local tumor viability and growth was quantified by bioluminescence imaging pre and 48 h post-treatment. PDT demonstrated an ablative effect on vertebral metastases (light energies 25-150 J). The effect varied in proportion to light energy with the greatest anti-tumor effect observed at 150 J using a 3 h drug-light interval. 9/22 rodents in the 3 h drug-light interval developed hindlimb paralysis following treatment, consistent with drug uptake studies demonstrating an increase in spinal cord uptake 3h following drug administration. The observations of paralysis following treatment highlight the importance of closely defining the therapeutic window of treatment in safety and efficacy.     

Acute hemodynamic responses to electroconvulsive therapy are not related to the duration of seizure activity

Study Objective: To test the hypothesis that the magnitude of the acute hemodynamic response to electroconvulsive therapy (ECT) is related to the duration of the seizure activity in patients receiving different dosages of intravenous (IV) lidocaine.

Design: Randomized, double-blind, placebo-controlled, cross-over study.

Setting: University-affiliated hospital.

Patients: 21 ASA physical status I, II, and III patients undergoing four consecutive maintenance ECT treatments for chronic depression.

Interventions: Patients received lidocaine 50 mg, 100 mg, 200 mg IV, or saline prior to induction of anesthesia via a standardized anesthetic technique.

Measurements and Main Results: Noninvasive blood pressure (BP) and heart rate (HR), as well as the duration of motor and electroencephalographic (EEG) seizure, were measured. The duration of motor and EEG seizures (means ± SD) were 37 ± 13 sec and 64 ± 21 sec, 25 ± 11 sec and 52 ± 43 sec, 17 ± 12 sec and 32 ± 17 sec, 1 ± 3 sec and 18 ± 10 sec in the saline, lidocaine 50 mg, 100 mg, 200 mg groups, respectively. Although the duration of seizure activity was decreased in a dose-related fashion after lidocaine pretreatment, the peak increases in BP and HR were similar in the lidocaine and saline treatment groups.

Conclusions: Despite producing dose-related decreases in the duration of both motor and EEG seizure activity, lidocaine failed to attenuate the acute hemodynamic response to ECT. Thus, the acute hemodynamic response to ECT is not related to the duration of seizure activity.     

Hyperbaric oxygen therapy in the management of severe acute anaemia in a Jehovah's Witness

A case is described in which a Jehovah's Witness patient who refused blood transfusion suffered massive antepartum haemorrhage, her haemoglobin falling as low as 2.0 g.dl(-1). She was treated on an intensive care unit with intermittent positive pressure ventilation and general supportive measures, pulsed hyperbaric oxygen therapy and recombinant human erythropoietin.