Combination therapy using prednisolone and cyclophosphamide slows the progression of moderately advanced IgA nephropathy

AIM: We retrospectively examined the effect of combination therapy using prednisolone (PSL) and cyclophosphamide (CPA) on the progression of IgA nephropathy (IgAN) in 45 patients with moderate to severe histological changes. PATIENTS AND METHODS: Patients were recruited from 129 consecutive patients with IgAN seen over 10 years based on semiquantitative histological grading. They were divided into two groups: PSL+CPA group (n = 26, male/female = 11/15, age 40+/-3 years (SEM)) or control group undergone conventional therapy with or without antiplatelet agents (n = 19, male/female = 10/9, age 41+/-3). In PSL+CPA group, PSL and CPA treatment commenced using a dose of 30 and 50 mg/day, respectively. PSL was reduced by 5 mg every month. RESULTS: The clinical parameters at the start of treatment such as age, gender, histological score, blood pressure, urinary protein excretion and serum creatinine concentration (SCr) were not different between the groups. The mean observation period in PSL+CPA group (3.3+/-0.3 years) was not different from the control group (4.0+/-0.7 years). In PSL+CPA group, urinary protein excretion, defined as the ratio of urinary protein to creatinine concentration (UP/UCr), significantly decreased from 3.9+/-0.4 to 1.3 +/-0.2 (p<0.01), whereas it remained high in the control group (3.8+/-0.7 to 2.7+/-0.8). The progression rate (PR), which was determined by the slope of the correlation between time after renal biopsy and reciprocal SCr, was significantly lower in PSL+CPA (0.054+/-0.014) than in the control group (0.172+/-0.032 dl/mg/year, p<0.001). Our results indicated that PSL+CPA combination therapy was effective in slowing the progression of moderately advanced IgAN. CONCLUSION: We suggest that the immunosuppressive treatment with CPA is sometimes necessary to preserve renal function in patients with histologically advanced IgAN.     

Nationwide survey on current treatments for IgA nephropathy in Japan

Background

A wide variety of treatments, including tonsillectomy and steroid pulse therapy (TSP), are performed for the various stages of IgA nephropathy (IgAN) in Japan. However, the current status of treatments for IgAN patients in Japan is still unclear. The objective of the present study was to investigate the current status of treatments for IgAN patients.

Methods

A nationwide survey was conducted in 2008 by sending questionnaires to the 1,194 teaching hospitals of the Japanese Society of Nephrology (JSN) via Progressive Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan.

Results

Among the total 376 hospitals (31.4 %) that responded, 188 hospitals (66.2 % in the internal medicine departments) performed TSP, out of which 137 hospitals (61.4 %) had begun to perform TSP in the period from 2004 to 2008. The following two major steroid pulse protocols in TSP were used: (1) three cycles over 3 consecutive weeks and (2) three cycles every 2 months. Approximately 68 % of pediatric hospitals (68 hospitals) performed combination therapy with prednisolone, azathioprine, heparin-warfarin and dipyridamole. The clinical remission rates for hematuria and proteinuria after TSP tended to be higher than those following other corticosteroid therapies. Almost all hospitals prescribed antiplatelet agents and renin angiotensin system inhibitor (RAS-I).

Conclusion

In addition to popular treatments such as antiplatelet agents and RAS-I, TSP is becoming a standard treatment for adult IgAN patients in Japan.     

Effects of co-administration of urokinase and benazepril on severe IgA nephropathy.

BACKGROUND: The availability of treatment for IgA nephropathy (IgAN) is limited. Method. A prospective randomized controlled clinical trial was performed to evaluate the effects of therapy with urokinase (UK) and benazepril (BZ, an angiotensin-converting enzyme inhibitor) or BZ alone on severe IgAN. We divided 71 cases of IgAN, Lee's grade >/=III and with fibrinogen deposits, into two groups to be treated for 12 months with either UK + BZ or BZ alone. RESULTS: There was no significant difference between the two groups in baseline clinical and histopathological data. After 12 months of treatment, 25 of 35 patients (71.4%) in the UK + BZ group and 16 of 36 (44.4%) in the BZ-alone group had a >/=50% decrease in 24-h urinary protein excretion compared with the baseline (chi(2) test, P<0.05). Proteinuria significantly decreased at 6 and 12 months of treatment in both groups compared with baseline (P<0.01 in the UK + BZ group, P<0.05 in the BZ group), and the therapeutic efficiency of UK + BZ was better than that of BZ alone (P<0.05 at 6 and 12 months). The endogenous creatinine clearance rate (Ccr) was stable in the UK + BZ group, while Ccr declined significantly at 6 and 12 months in the BZ-alone group compared with baseline (P<0.05, respectively). The Ccrs of the two groups at 12 months of treatment were statistically different (P<0.05). CONCLUSIONS: Combined therapy with UK and BZ was more effective than with BZ alone in reducing proteinuria and protecting renal function in patients with severe IgAN.     

尿激酶联合苯那普利治疗IgA肾病的随访对照研究

目的 观察联合应用尿激酶(UK)和血管紧张素转换酶抑制剂(ACEI)苯那普利治疗IgA肾病(IgAN)的效果。方法 将71例Lee分级≥Ⅲ级的IgAN患者随机分为两组:UK+ACEI组及ACEI组,随访观察两组的疗效。结果 (1)12个疗程后,UK+ACEI组24h尿蛋白定量明显下降(P<0.01),血白蛋白(AIb)水平升高(P<0.05),疗效优于ACEI组。(2)治疗前应用Katafuchi IgA肾病积分系统进行IgAN的病理评分,在肾小球积分≥7分的患者中,治疗至12个疗程时,UK+ACEI治疗效果优于ACEI组(P<0.05)。(3)UK+ACEI组中有10例患者进行了重复肾活检,经治疗后多数患者病理改变保持稳定。结论 UK联合ACEI治疗中重度IgAN安全有效,疗效优于单用ACEI者。肾小球硬化及间质炎细胞浸润的程度可作为估计UK治疗IgAN效果的指标。     

Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients

Background

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20–40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.

Methods

We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).

Results

There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 ± 4.4 vs. 9.9 ± 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).

Conclusions

In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

     

Initial treatment with pulse methylprednisolone followed by short-term prednisolone and tonsillectomy for childhood IgA nephropathy

Background

Although a combination therapy, comprising 2-year high-dose oral prednisolone (PSL), is effective for treating childhood immunoglobulin A nephropathy (IgAN), severe adverse effects and residual proteinuria occur in some patients after the therapy.

Methods

To clarify the efficacy of intravenous pulse methylprednisolone (IVMP; 15–20 mg/kg; maximum 600 mg/day; for 3 consecutive days/week for 3 weeks) followed by short-term reduced-dose PSL (initially 1 mg/kg; maximum 30 mg on alternate days; tapered off within approximately 12 months) and tonsillectomy as an initial treatment, we retrospectively reviewed the clinical courses of 54 consecutive children with IgAN (32 boys; mean age at onset, 12.2 years; follow-up period of >?2 years) after initiating the treatment. According to the Japanese pediatric IgAN guidelines, we divided the 54 patients into the following two groups: group 1, comprising 24 patients with severe IgAN, and group 2, comprising 30 patients with mild IgAN.

Results

After the treatment, proteinuria disappeared in all patients at a median of 1.6 months (group 1, 2.8 months; group 2, 0.4 months) and hematuria disappeared in 47 patients (87%) at a median of 13.2 months (group 1, 15.9 months; group 2, 13.2 months). During the follow-up period (median 5 years), no severe adverse effects were observed in any patient. At the last visit, although two patients (4%) had mild proteinuria, none developed hypertension or renal insufficiency.

Conclusions

As an initial treatment, IVMP followed by short-term PSL and tonsillectomy appears to be effective for treating childhood IgAN.

     

Mycophenolic acid therapy after cyclophosphamide pulses in progressive IgA nephropathy

BACKGROUND: In progressive IgA nephropathy (IgAN), cyclophosphamide or steroids have been used to reduce the loss of renal function, but disease progression may occur after the end of treatment. The value of mycophenolic acid (MPA) maintenance therapy following initial immunosuppression in progressive IgAN is largely unknown. METHODS: In a prospective single-center trial, 20 patients with advanced IgAN (median glomerular filtration rate [GFR], 22 ml/min) and disease progression after cyclophosphamide pulse (CyP; n=18) or steroid pulse therapy (n=2) were treated with MPA for a median of 27 months. MPA dosages (initially mycophenolate mofetil 500 mg twice daily) were adjusted according to predose plasma concentrations (target concentrations 1.5 to 4 microg/mL). The course of renal function was assessed by linear regression of glomerular filtration rates. RESULTS: Median loss of renal function per month was significantly reduced from -0.8 ml/min to -0.03 ml/min per month after 6 months, to -0.05 ml/min per month after 12 months, and to -0.12 ml/min per month at the end of the study after median 27 months (p<0.05). An improved or stable GFR was observed in 16 of 20 patients during the first 12 months, and sustained in 10 patients during 24 months of follow-up. Proteinuria decreased significantly from 1.1 g/L to 0.4 g/L during MPA treatment (p=0.018). CONCLUSION: Our results indicate that MPA may be beneficial to slow down the loss of renal function in patients with progressive IgAN after previous immunosuppressive treatment.     

Treatment of IgA nephropathy

IgA nephropathy (IgAN) is an important cause of progressive kidney disease with 25-30% of patients developing end-stage renal disease within 20 years of diagnosis. There is still no treatment to modify mesangial IgA deposition and available treatments are those extrapolated from the management of other patterns of chronic glomerulonephritis. There remains no consensus on the use of immunosuppressive agents for treatment of progressive IgAN and this is compounded by the relative lack in IgAN of randomized controlled trials relevant to current clinical practice. Patients with recurrent macroscopic hematuria or isolated microscopic hematuria and proteinuria <1 g/24 h require no specific treatment. Those with nephrotic syndrome and minimal change on renal biopsy should be managed as for minimal change nephropathy. There is no evidence to support the use of corticosteroids for nephrotic IgAN outside this group of patients. Patients presenting with acute renal failure require evaluation to distinguish acute tubular necrosis, which requires supportive therapy only, from crescentic IgAN, for which treatment with cyclophosphamide and corticosteroids in a regimen similar to that for renal small vessel vasculitis is indicated in the absence of significant chronic histologic injury. Patients at greatest risk of progressive renal impairment are those with hypertension, proteinuria >1 g/24 h, and reduced glomerular filtration rate at diagnosis. All such patients should be treated to a blood pressure of 125/75 mm Hg with dual blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibition and angiotensin receptor blockade. At present, there is insufficient evidence for the additional use of immunosuppressive agents, antiplatelet agents, or anticoagulants.     

Antiplatelet therapy early after bioprosthetic aortic valve replacement is unnecessary in patients without thromboembolic risk factors.

BACKGROUND: The use of antithrombotic therapy during the postoperative period after biological aortic valve replacement (AVR) in patients without thromboembolic risk factors remains controversial. Treatment with warfarin is recommended for the first 3 months after biological AVR. The use of antiplatelet therapy - mainly aspirin (ASA) - is suggested as an alternative treatment but its efficacy is still unsettled. Due to the increased risk of bleeding complications even no use of any antithrombotic or antiplatelet therapy was advocated. Given this ongoing dispute, the aim of this retrospective double-institutional study was to evaluate the necessity of antiplatelet treatment by ASA with no postoperative antiplatelet therapy in terms of survival, major bleedings and cerebral thromboembolism of patients undergoing biological AVR without thromboembolic risk factors. METHODS: From January 2001 to December 2003, 288 consecutive patients (72.8+/-7.5 years, 134 males) with sinus rhythm and no other thromboembolic risk factors underwent single biological AVR with porcine or bovine pericardial valves without concurrent coronary artery bypass graft surgery. By surgeons preference, 100 mg ASA was given to 132 patients, and 156 patients received no antiplatelet therapy. Patients were followed for cerebral ischemic events, major bleedings, need for repeat operation, NYHA class and survival at three time intervals postoperatively (30 days, 3 and 12 months). RESULTS: None of all patients died during the operation. Mortality within 30 days was 3.8% in the ASA and 3.9% in the no ASA group (p=0.777). There were no statistically significant differences for cerebral ischemia within 3 months after AVR (ASA 0.8% vs no ASA 1.3%: p=0.884) and 3 to 12 months after AVR (ASA 0.8% vs no ASA 0%; p=0.933). Major bleedings occurred in two ASA-treated patients and in one patient without antiplatelet therapy (p=0.884). The incidence of NYHA class III-IV after 3 months (1.5% vs 1.9%; p=0.850) and 12 months (9.0% vs 5.1%; p=0.278) were similar, as were the need for repeat operative AVR after 12 months (0.8% vs 0.6%; p=0.553). Survival rates at 12-month follow-up were 95.5% for ASA treatment and 94.9% for no ASA treatment (p=0.963). CONCLUSIONS: In patients without thromboembolic risk factors undergoing biological AVR administration of ASA confers no advantage compared to no antiplatelet therapy. Functional status, thromboembolic events and survival were not adversely affected by withholding any antiplatelet therapy. Guidelines need to be reviewed for the antithrombotic therapy of patients without risk factors undergoing bioprosthetic AVR.     

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.     

Alternate-day prednisone therapy in children with IgA-associated nephritis

IgA nephropathy (IgAN) leads to renal failure in up to 30% of affected children and adults. There is currently no consensus on therapy in IgAN. Six patients with risk factors for disease progression were identified based on clinical or histologic findings. These patients were treated with alternate-day prednisone for 12 to 60 (mean, 36) months and followed for 28 to 60 (mean, 54) months. Follow-up biopsies were available in four patients. At last examination all treated patients had normal urinalysis and serum creatinine level. Follow-up biopsies showed stable or improved glomerular histology in three of four patients. One patient had a slight worsening of the interstitial disease. No steroid toxicity was observed. The outcome of these treated patients was compared with that of 15 comparable patients from another center who received no treatment and with patients from two published clinical pathology series. A normal urinalysis was found at follow-up in all treated patients, compared with one of 15 untreated patients (P = 0.003). None of the patients in the published series with comparable disease had normal urinalysis at follow-up. End-stage renal disease or renal insufficiency occurred in seven of 15 untreated and no treated patients (P = 0.19). The data strongly support the need for a prospective control trial of prednisone therapy in IgAN.     

Comparison of long-term follow-up outcomes between multiple-drugs combination therapy and tonsillectomy pulse therapy for pediatric IgA nephropathy

Background

To clarify the long-term efficacy of multiple-drugs combination therapy (PWDM) and tonsillectomy pulse therapy (TPT) for pediatric IgA nephropathy (IgAN), we retrospectively evaluated the clinical and laboratory findings as well as the prognosis for IgAN patients treated with each treatment at long-term follow-up.

Methods

We collected data on 61 children who had been diagnosed with severe IgAN. The children were retrospectively divided into two groups. Group 1 consisted of 44 severe IgAN children treated with PWDM, and Group 2 consisted of 17 severe IgAN children treated with TPT. The clinical features, pathological findings, and prognosis were analyzed for both groups.

Results

The mean urinary protein excretion, serum creatinine, IgA levels, MESTCG scores, and percentage of glomeruli showing crescents in both groups at the second renal biopsy were lower than those at the first renal biopsy. At the time of the second biopsy, the IgA level in Group 2 was lower than that in Group 1; however, there were no significant differences in the mean urinary protein excretion, frequency of hematuria, serum albumin, creatinine, or e-GFR between the two groups. At the most recent follow-up, there were no significant differences in prognosis between the groups.

Conclusions

Our study suggested that PWDM and TPT are effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN.

     

Severity of nephrotic IgA nephropathy according to the Oxford classification

Background

IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused.

Methods

In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy.

Results

In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1?±?24.6?ml/min, proteinuria was 5.71?±?2.56?g/day, and urinary red blood cells were 51.0?±?37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P?Conclusion Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.     

The effect of postoperative anticoagulation on microvascular thrombosis

BACKGROUND: Numerous protocols exist to prevent thrombosis after free-tissue transfer. Many surgeons advocate using aspirin or other antiplatelet agents, but little objective evidence supports this practice. This study evaluates the rate of microvascular thrombosis in patients undergoing free-tissue transfer treated with or without antiplatelet agents. METHODS: All consecutive free flaps from 2002-2005 at a single center were reviewed using a prospectively maintained database. Patients were in 2 groups based on postoperative anticoagulation administration. In group 1, 325 mg of aspirin was administered daily for 5 days postoperatively. In group 2, patients were treated with 5000 units of low-molecular-weight heparin (LMWH) per day until ambulating. Patient demographics, procedure type, diagnosis, adjuvant treatment, and procedure type were recorded. Outcome variables included microvascular thrombosis, partial or total flap loss, hematoma, bleeding, deep venous thrombosis (DVT), pulmonary embolism, and death. RESULTS: Four hundred seventy patients underwent 505 microvascular free flaps to reconstruct oncologic defects. Two hundred sixty flaps (group A) received postoperative aspirin therapy; 245 flaps (group B) received LMWH therapy. Both groups were statistically similar in their composition. No statistically significant difference was noted between the 2 groups when comparing outcome variables including microvascular thrombosis, partial or total flap loss, hematoma, bleeding, DVT, pulmonary embolism, and death. CONCLUSIONS: Postoperative anticoagulation choice has no statistically significant effect on the incidence of free flap complications, including bleeding, thromboembolism, and flap loss. We conclude that aspirin or LMWH therapy demonstrates equivalent outcomes when used as single-agent postoperative anticoagulation in oncologic free flap reconstruction.     

Lipid peroxidation in IgA nephropathy and the effect of lipo-prostaglandin E1

BACKGROUND: Lipid peroxidation (LPO) plays a role in glomerulonephritis pathogenesis. The role of LPO in IgA nephropathy (IgAN) and the effect of prostaglandin E1 on it, is not determined. METHODS: Levels of malondialdehyde (MDA), superoxide dismutase (SOD) and vitamin E (vitE) were measured in 42 patients with IgAN and in 31 healthy controls. Clinical nephropathy parameters such as daily proteinuria (DP), serum creatinine (Cr) and Cr clearance were obtained. Forty-two IgAN patients were divided into two subgroups according to renal pathology severity. Twenty-one patients with IgAN received lipo-prostaglandin E1 (PGE1) treatment and the other 21 patients received saline as a control. RESULTS: The serum activity of SOD and vitE in IgAN patients was significantly lower than in healthy controls, while the MDA level was higher in the patient groups. DP-related positively to MDA, while it related negatively to SOD and vitE. Cr clearance related negatively to MDA, while it related positively to SOD and vitE. In the moderate pathological group, the MDA level was significantly higher and the SOD activity was lower than in the mild pathological group. The MDA level in the PGE1 treated group was lower than in the control group, but the activity of SOD and vitE did not differ significantly from the control group. DP declined and Cr clearance increased in the PGE1 treated group, while no significant change in serum Cr was noted. CONCLUSIONS: LPO in IgAN was evident and was at least attributed to the decline in antioxidant ability. LPO could play a role in IgAN pathogenesis, and PGE1 is able to ameliorate the LPO in IgAN patients.     

Antiplatelet therapy: an alternative to heparin for blunt carotid injury

BACKGROUND: Blunt carotid injuries (BCIs) are uncommon. Most single-center studies are small and highlight the use of anticoagulation for treatment. In a retrospective review, we identified 22 patients who presented with BCI and assessed neurologic and survival outcomes on the basis of injury grade and treatment with anticoagulation or antiplatelet therapy. METHODS: Patient demographics were identified using the trauma registry at a single Level I trauma center. Chart reviews assessed neurologic function, modalities used for diagnosis, and treatment. Neurologic outcomes were graded good (minimal to no deficit), fair (moderate deficit needing some assistance), poor (requiring institutionalization), and dead. RESULTS: Twenty-two adult trauma patients were diagnosed with BCI, for an incidence of 0.45% in the 8-year study period. All BCI patients underwent head computed tomography and four-vessel cerebral arteriography. Eight patients were not anticoagulated, five because of intracranial injuries, two who had surgical CCA repairs, and one with an aortic injury. Full anticoagulation with heparin was attempted in seven patients, with four major bleeding complications requiring cessation of heparin and blood transfusions. Seven patients received antiplatelet therapy. No difference in neurologic outcome was observed between those receiving anticoagulation and those receiving antiplatelet therapy. Bleeding complications from full anticoagulation were higher than with antiplatelet agents (p = 0.05). CONCLUSION: Contrary to previous reports, we did not observe improved outcomes with full anticoagulation compared with antiplatelet therapy. Anticoagulation was associated with increased extracranial bleeding complications. The risks and possible benefits, as well as timing, of anticoagulation or antiplatelet therapy for BCI should be carefully weighed by the major care providers of the patient with multiple injuries.     

Monitoring aspirin 100 mg and clopidogrel 75 mg therapy with the PFA-100 device in patients with peripheral arterial disease

A tool to identify vascular patients who receive antiplatelet therapy nd to distinguish between responders and non-responders to antiplatelet therapy could be of clinical importance. The present observational study was designed to investigate whether the PFA-100 device (Dade Behring) is suitable to detect long-term therapy of aspirin (100 mg/d) and/or clopidogrel (75 mg/d) in a cohort of patients with peripheral arterial disease (PAD). A total of 150 consecutive patients with PAD were studied; 34 patients were excluded from the study due to irregular intake of antiplatelet therapy or due to method limitations. Of the remaining 116 patients, 42 had no antiplatelet therapy, 47 had daily aspirin (100 mg) intake, 19 were administered clopidogrel 75 mg daily, and 10 received a medication with 100 mg aspirin plus clopidogrel 75 mg daily, all for at least 10 days. Nonparametric Kruskal-Wallis test with post hoc comparisons showed that collagen plus epinephrine (CEPI) closure times of the patient group receiving aspirin and the group receiving aspirin plus clopidogrel were similar (p>0.05). In contrast, both patient groups exhibited prolonged CEPI values compared to patients without antiplatelet therapy and patients taking clopidogrel (p<0.001). Finally, both patients without antiplatelet therapy and patients with clopidogrel did not show marked differences with respect to their CEPI values (p>0.05). However, Kruskal-Wallis test results revealed that collagen plus adenosine-5'-diphosphate closure times were not significantly different in all four patient groups (p=0.257). In conclusion, the PFA-100 device may be a suitable tool for monitoring aspirin 100 mg therapy, but it is not appropriate for the detection of clopidogrel administration in its current setup. Although it appears plausible that patients with PAD could benefit from monitoring platelet inhibition, clear evidence for this concept is still lacking.     

Long-term follow-up of patients with IgA nephropathy treated with prednisolone and cyclophosphamide therapy

BACKGROUND: Analyses of selected cases suggest that immunosuppressive treatment could reduce proteinuria and delay the progression of immunoglobulin A nephropathy (IgAN). The aim of this study was to examine the long-term effectiveness of this therapy on the clinical course of IgAN. We also examined the relationship between the efficacy of the treatment and the suppression of the serum immunoglobulin level. METHODS: Eighteen patients who were observed for more than 2 years after prednisolone and cyclophosphamide therapy were enrolled in this study. Their clinical and laboratory characteristics were recorded for 2-18 years (mean 7.8 +/- 5.7 years). RESULTS: Of the 18 patients, 13 had remission of proteinuria. We observed the subsequent development of proteinuria in four patients. Fourteen patients had remission of hematuria, with five patients experiencing subsequent relapse of hematuria. The mean time from the treatment to the relapse of proteinuria or hematuria was 5.8 years. Serum immunoglobulins were suppressed by the combination therapy. Serum IgG and IgM recovered 6 months after the treatment, whilst the suppression of serum IgA lasted for 4 years. We found a positive correlation between the serum IgA level and the degree of proteinuria. CONCLUSION: This study indicates that long-term follow-up is essential in order to prove the long-term benefit of immunosuppressive therapy in patients with IgAN. Careful monitoring of the serum IgA level may be useful in the follow-up of patients with IgAN, especially when they are treated with immunosuppressive agents.     

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目的 评价鸦胆子油“夹馅法”栓塞治疗与瘤内注射免疫因子联合治疗中晚期原发性肝癌和晚期肺癌的临床疗效。方法 将４３例中晚期不能切除的肝癌病人及６４例晚期肺癌病人分为两组。Ａ组５５例,在给予瘤内局部注射免疫因子治疗同时,分别交替进行经肝动脉鸦胆子油－碘油－抗癌剂“夹癌剂”栓塞化疗（ＴＡＥ）或经支乞管动脉藻注化疗（ＢＡＩ）。Ｂ组５２例单纯给予ＴＡＥ和ＢＡＩ治疗。结果 两组完全缓解率,生存率均有显著差异。     

Efficacy of tonsillectomy pulse therapy versus multiple-drug therapy for IgA nephropathy

We evaluated the efficacy of tonsillectomy plus pulse prednisolone, warfarin, and dipyridamole including methylprednisolone pulse (tonsillectomy plus pulse therapy), versus prednisolone, warfarin, and dipyridamole including mizoribine (PWDM) for the treatment diffuse IgA nephropathy (IgAN) in children. The patients were randomly assigned to be treated by tonsillectomy plus pulse therapy for 2 years (Group A, n=16) or PWDM for 2 years (Group B, n=16). The clinical features and pathological findings in both groups were analyzed prospectively. The mean urinary protein excretion after 6 months of treatment in both groups had decreased significantly compared with pre-therapy. The activity index (AI) in both groups was lower at the time of the second biopsy than at the time of the first biopsy. The chronicity index (CI) in Groups A and B did not differ between the first and second biopsy. At the latest follow-up examination none (0%) of the patients in either group had renal insufficiency. None of the patients in Group A, but six patients in Group B experienced an acute exacerbation of IgAN as a result of tonsillitis (P<0.05). In conclusion, although there was no untreated control group in this study, the results suggested that tonsillectomy plus pulse therapy is as effective as PWDM in ameliorating proteinuria and histological severity in IgAN patients and in preventing acute exacerbation of IgAN by tonsillitis.