Clinicopathologic findings relevant to disappearance or relapse of proteinuria following corticosteroid treatment in IgA nephropathy patients with proteinuria of 0.5 to 2.0 g/day

Background We investigated the clinical and pathological findings relevant to the efficacy of corticosteroid treatment in IgA nephropathy patients with 0.5 to 2.0g/day of proteinuria at the initiation of corticosteroid treatment.Methods In 27 IgA nephropathy patients who received 2-year prednisolone treatment, we analyzed the differences in clinical and pathological parameters (1) between patients with and without disappearance of proteinuria (less than 0.15g/day), and (2) between patients with and without relapse of proteinuria (more than 0.5g/day) at the end of follow-up.Results The levels of proteinuria and mesangial proliferation at the initiation of prednisolone treatment were significantly lower in patients with disappearance of proteinuria at the end of follow-up than in those without. The levels of active extraglomerular lesions and tubulointerstitial mononuclear cell infiltration and/or fibrosis, and the activity index, were significantly higher in patients with relapse of proteinuria than in those without.Conclusions In IgA nephropathy patients with 0.5 to 2.0g/day of proteinuria, disappearance of proteinuria following 2-year prednisolone treatment can be expected in patients with less proteinuria and less mesangial proliferation at the initiation of the prednisolone treatment. Furthermore, active extraglomerular lesions, the activity index, and tubulointerstitial cell infiltration and/or fibrosis appear to be more suitable risk markers for relapse of proteinuria than the initial levels of proteinuria.     

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed hump electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.     

Combined effects of Inversed Ratio Ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure

Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure (PEEP) on cardiorespiratory function were examined in 24 patients with acute respiratory failure. Patients were divided into two groups: the IRV group (n = 12) who showed no significant increase in Pa_{O 2} with a 6cmH₂O of PEEP and PEEP group (n = 12) who were ventilated mechanically with PEEP only at maximum level of 10cmH₂O. In IRV group step-wise prolongation of the I:E ratio from 1:1.9 to 2.6:1 or 4:1 was applied as a Pa_{O 2} was improved and in PEEP group also level of PEEP was increased from 0, 5 to 10cmH₂O after one hour period irrespective of Pa_{O 2}. Inversed ratio ventilation and PEEP increased significantly Pa_{O 2}/Fi _{O 2}, the increase being observed 6hrs (I:E = 2:1) and 2hrs (10cmH₂O) after starting IRV or PEEP. Further improvement of oxygenation was not observed in IRV even if I:E ratio was prolonged up to 2.6:1 or 4:1. These results suggested that combinations of IRV with PEEP were effective and an I:E ratio of 2:1 may be optimal, and IRV is advantageous compared to PEEP, but will take more long time to improve oxygenation than PEEP.(Sari A, Toriumi T, Yamashita S, et al.: Combined effects of inversed ratio ventilation (IRV) with positive end-expiratory pressure ventilation (PEEP) on cardiorespiratory function in acute respiratory failure. J Anesth 5: 105–113, 1991)     

Hypocomplementemia and membranoproliferative glomeruloneophritis in children

Background The incidence of hypocomplementemia detected in the school urinary screening program in Kanagawa Prefecture, Japan, and the number of new patients with membranoproliferative glomerulonephritis (MPGN) diagnosed in our institution were decreasing during the period between 1974 and 1997. Follow-up of this study was performed during the period between 1998 and 2003.Methods A total of 1230398 urine specimens in elementary and junior high school were examined between 1980 and 2003. Serum C3 was measured in children with abnormal urinary findings. Fifty-nine children were diagnosed as having idiopathic MPGN in our hospital between 1974 and 2003.Results Serum C3 was measured in 1546 school children with abnormal urinary findings, and 34 had hypocomplementemia between 1980 and 2003. Among 264 children in whom C3 was measured between 1998 and 2003, only 4 had mild hypocomplementemia of 83–86mg/dl (normal, 87–157mg/dl). Between 1974 and 2003, 59 children (8.8%) were diagnosed as having idiopathic MPGN in our hospital, whereas only 2 were diagnosed during the period between 1998 and 2003.Conclusions The incidence of hypocomplementemia detected in school urinary screening and new cases of MPGN continue to decrease in our experience.     

The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis

A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8mg/dl) and creatinine (3.4mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500mg/day, 3 days) and 45mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11EU/ml to 116EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.     

The effectiveness of steroid therapy for patients with advanced IgA nephropathy and impaired renal function

Background Recent studies have shown that steroid therapy is effective for IgA nephropathy (IgAN) in patients with moderate proteinuria and active histological findings. However, the effectiveness of steroid therapy has not been determined yet in patients with advanced IgAN and impaired renal function.Methods Sixty IgAN patients whose creatinine clearance was under 70ml/min at the time of renal biopsy were studied retrospectively. The patients were divided into two groups according to treatment: a steroid group (n = 20) and a nonsteroid group (n = 40). The mean age was 39.6 ± 14.9 years in the steroid group and 40.6 ± 10.9 years in the nonsteroid group. The mean follow-up period was 4.5 ± 2.2 years in the steroid group and 4.6 ± 2.4 years in the nonsteroid group. Patients with high proteinuria and high histological activity were treated with prednisolone. Clinical and histological findings before treatment and the outcome after treatment were analyzed.Results In the retrospective analysis, the amount of urinary protein excretion before treatment tended to be higher in the steroid group than in the nonsteroid group, but was not significantly different (2.33 ± 1.54 vs 1.39 ± 1.87g/day). Histologically, the percentage of patients with crescent formation, especially that of cellular or fibrocellular crescents, was significantly higher in the steroid group than in the nonsteroid group (17.2 ± 15.9% vs 2.3 ± 4.5%; P < 0.0001). The grades of mesangial cell proliferation (1.65 ± 0.55 vs 1.21 ± 0.47; P = 0.002) and mesangial matrix increase (1.88 ± 0.64 and 1.41 ± 0.67; P = 0.01) were higher in the steroid group than in the nonsteroid group. In the evaluation of the outcome after treatment, the amount of urinary protein excretion at 1 year after treatment had significantly decreased in the steroid group (before treatment, 2.33 ± 1.54g/day; at 1 year, 1.02 ± 0.98g/day; P = 0.003), but the amount remained unchanged in the nonsteroid group (before treatment, 1.39 ± 1.87g/day; at 1 year, 1.28 ± 2.19g/day). The levels of serum creatinine before treatment and at 1 year after treatment were not changed in either of the groups, however, in the nonsteroid group, the level at the final observation was significantly higher than the level before treatment (2.51 ± 3.43 vs 1.27 ± 0.33mg/dl; P = 0.0219).Conclusions In the present study, in advanced IgAN patients whose creatinine clearance was under 70ml/min, steroid therapy effectively reduced the amount of proteinuria and maintained the serum creatinine level, if the treatment was selectively applied to patients with a moderate amount of proteinuria and active glomerular lesions such as cellular and fibrocellular crescents, and mesangial cell proliferation.     

Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

Ischemic Preconditioning Reduces Caspase-Related Intestinal Apoptosis

Purpose To investigate the preventive effect of ischemic preconditioning (IPC) on ischemia/reperfusion (I/R)-induced apoptosis and injury in the rat intestine.Methods We divided 30 male Wistar rats, weighing 300–350g, randomly into three groups. The control group rats (n = 10) were subjected to laparotomy only; the I/R group (n = 10) rats were subjected to occlusion of the superior mesenteric artery for 45min, followed by reperfusion for 60min; and the IPC group (n = 10) rats were subjected to IPC, achieved with two cycles of 5min ischemia and 5min reperfusion immediately before the I/R, as in the I/R group. Blood samples were collected by cardiac puncture, to measure nitrate and myeloperoxidase (MPO) levels. Histopathological and immunohistochemical studies were done to evaluate the I/R-induced apoptosis and injury.Results The blood MPO and nitrate levels were increased in the I/R group, but IPC prevented their increase. There were significantly fewer apoptotic cells in the IPC group than in the I/R group, and this finding was supported by the caspase-3 expression in the ileum. The intestinal histopathology was also protected by IPC against I/R-induced injury.Conclusion Ischemic preconditioning clearly prevented I/R-induced injury and apoptosis by a mechanism related to the caspase-3-dependent pathway. We also showed that IPC inhibited leukocyte activation, with the suppression of myeloperoxidase levels in I/R and nitric oxide-related oxidoinflammatory pathway upregulation.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

Prevalence of high fasting plasma glucose and risk of developing end-stage renal disease in screened subjects in Okinawa,Japan

Background The number of diabetic dialysis patients is increasing worldwide. Only a few studies, however, have examined the effect of diabetes mellitus (DM) as a risk factor for the development of end-stage renal disease (ESRD) in the general population.Methods We examined the cumulative incidence of ESRD based on the results of community-based mass screening in Okinawa, Japan, performed in 1993 by the Okinawa General Health Maintenance Association. Fasting plasma glucose (FPG) data were available for 78529 screenees (37197 men and 41332 women). DM was diagnosed when the FPG was 126mg/dl or more. Screenees who developed ESRD by the end of 2000 were identified through the Dialysis Registry, Okinawa Dialysis Study.Results The mean (SD) FPG was 96.5 (22.8)mg/dl, ranging from 45 to 577mg/dl. The prevalence of DM among the screenees was 4089 (5.2%). A total of 133 screenees (82 men and 51 women) developed ESRD during the 7.75-year study period. The adjusted odds ratio (95% confidence interval [CI]) in the high-FPG group for the risk of developing ESRD was 3.098 (95% CI, 1.738–5.525; P = 0.0001), when adjusted for age, sex, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, triglyceride, hematocrit, serum creatinine, hematuria, and proteinuria.Conclusions The results of the present study indicated that FPG is a significant, independent predictor of ESRD. FPG and proteinuria measurements are euqally important in detecting individuals at high risk for developing ESRD.     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Spinal neurotoxicity and tolerance after repeated intrathecal administration of YM 872, an AMPA receptor antagonist,in rats

Purpose Although the -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM 872, has been considered to be useful in analgesia for both acute and chronic pain, there are no studies of its neurotoxicity and tolerance. We examined the spinal neurotoxicity and tolerance of YM 872 analgesia by repeated intrathecal administration in rats.Methods Male Sprague-Dawley rats with lumbar intrathecal catheters received YM 872 at 1µg·10µl^–1 (eight rats; YM group) or normal saline 10µl (eight rats; C group) intrathecally once a day for 30 days. We evaluated the analgesic effects every 3 days, by tail-flick test and behavioral side effects. On the 31st day, the lumbar spinal cord was removed from four randomly selected rats in each group for histological examination.Results The YM group showed significantly longer tail-flick latency when subjected to a high-intensity light beam than the C group at each measurement time point, although no significant changes in the latency according to the time course of the study were observed for the entire study period of 30 days in either group. No rats showed any side effects. Histologically, only slight lymphocytic cell infiltration and degeneration of myelinated fibers occurred, similarly in both groups. No changes were observed in the spinal cord in either group.Conclusion Administration of YM 872 (1µg) once a day for 30 days did not induce any tolerance and caused no histological changes in the spinal cord.     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)     

Safety of Contrast Venography prior to Caval Interruption in Patients with Renal Insufficiency

We undertook this study to determine whether the use of contrast venography would adversely affect renal function in patients with renal insufficiency requiring caval interruption. We conducted a retrospective review of all inferior vena cava (IVC) filters inserted at our institution over a 2-year period (January 2002 to January 2004). The indication for caval interruption, insertion technique, type of filter used, pre- and postintervention creatinine level, and the presence of diabetes and hypertension were analyzed. A total of 282 IVC filters were inserted, with 38 of them placed in patients with renal insufficiency as defined by a serum creatinine level of > 1.5 mg/dL. Contrast venography with 15 to 30 mL of iohexol (Omnipaque 300) was used in all cases, and no special measures other than proper hydration were used for renal protection. All filters were successfully deployed. The mean±SD preintervention creatinine level was 2.38±0.79 mg/dL. The mean±SD postintervention creatinine levels at 2 and 30 days were 2.26±0.45 mg/dL and 2.12±0.94 mg/dL, respectively. No patients required hemodialysis following caval interruption, and no adverse effect on renal function was noted. Contrast venography accurately delineates venous anatomy and facilitates proper caval filter placement with no apparent adverse effect on renal function. We believe contrast venography is safe even in the presence of renal insufficiency.     

Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Treatment outcomes and mortality of 94 patients with acromegaly

Summary Background. Due to new therapeutic modalities and modified therapeutic goals outcome of patients with acromegaly may change over time and differ by centre. We analysed treatment outcomes and mortality of our patients with acromegaly seen between 1971 and 2003.Method. The cohort consisted of 94 patients who had been followed for 0.3–31 years (mean 10.6 years). Remission criteria were a normalized IGF-I concentration, a nadir GH level during oral glucose load of <1.0µg/l and a random GH value of <2.5µg/l.Findings. Transsphenoidal surgery achieved remission in 80% of patients with micro-adenomas (<1cm), 65% with meso-adenomas (1cm to <2cm) and 27% with macro-adenomas (2cm). Patients with meso-adenomas operated on after 1995 tended to have a better outcome compared to those operated on before 1995 (Remission in 83% vs. 38%). Radiotherapy resulted in disease control in 22 of 47 patients (47%). Intramuscular depot formulation of octreotide (Sandostatin^® LAR^®) led to disease control in 17 of 26 patients (65%). After multimodal therapy persistent acromegalic activity remained in 18% of the patients; only one of them had an adenoma of <2cm. The standardized mortality ratio was 1.30 (95% CI 0.52–2.67) for patients in remission and 1.38 (95% CI 0.51–3.00) for patients with persistent acromegalic activity.Conclusions. Most patients with adenomas of <2cm can be expected to achieve remission by transsphenoidal surgery alone. Furthermore, virtually all patients with adenomas of <2cm and more than 80% of patients with adenomas of 2cm can be expected to achieve remission by adjuvant treatment. Aggressive multimodal therapy is critical in the management of acromegaly reducing mortality risk close to that of the general population.     

Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

Surgical Management of Renal Fibromuscular Dysplasia: Challenges in the Endovascular Era

Percutaneous transluminal renal angioplasty (PTRA) is the primary treatment for renal fibromuscular dysplasia (RFMD). Surgical revascularization is limited to patients who fail or are unsuitable for PTRA. All patients who were operated on with RFMD since the indications for renal PTRA were expanded in our institution were retrospectively reviewed. Outcome included patency, hypertension, and renal function. Twenty-six patients had reconstruction of 32 renal arteries between 1998 and 2004. The mean age was 47.1±14 years; the majority (81%) were female. Six patients had bilateral disease and three had a solitary kidney. Operations were done for hypertension in 25 patients, renal artery aneurysm in 8, and chronic dissection in 1, alone or in combination. Six patients had a failed PTRA and 20 were unsuitable for it. Aortorenal bypass was done most often (n=28) and saphenous vein was the preferred conduit (n=25). The distal anastomosis was to the main renal artery in 13 patients and to the branch arteries in 19. Ex vivo repair was needed in five patients. Five intraoperative revisions were done because of abnormalities on duplex scan. One patient died unexpectedly 42 days after operation from myocardial infarction. Extrarenal complications occurred in five patients. Median follow-up was 2.4 (range, 42 days to 6.3) years and was available in all but one patient (96%). Two bypasses occluded at 3 and 376 days, which resulted in loss of the kidneys. One graft stenosis was treated successfully with PTRA at 239 days. All failures occurred in men. One-year cumulative primary patency was 89±8% and was not adversely affected by prior PTRA or complex repair. Hypertension at 1 year was cured in 27% of the patients and improved in 60%. No patient developed acute or chronic renal failure. Surgical reconstruction for RFMD has excellent short-term patency. Failed PTRA or complex reconstructions did not adversely affect outcome.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.