Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms

We describe five patients with treated low-grade B-cell neoplasms who subsequently developed Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders (BLPDs). The low-grade B-cell neoplasms were B-cell chronic lymphocytic leukemia in four patients and splenic marginal zone lymphoma in one patient. All patients had received treatment with fludarabine for the low-grade B-cell neoplasm, and three had also received Campath-1H. The EBV-BLPDs arose 2-12 months after completion of fludarabine therapy and morphologically resembled the EBV-BLPDs that occur in the setting of iatrogenic immunodeficiency. Molecular genetic studies showed that these lesions were clonally distinct from the low-grade B-cell neoplasm in three of four cases assessed. Two patients did not receive therapy for the EBV-BLPD. The lesions regressed spontaneously in both patients but recurred in one. One patient underwent surgical excision and remains without evidence of the EBV-BLPD. One patient received aggressive multiagent chemotherapy with a complete response initially, but the EBV-BLPD recurred after 12 months. One patient received antiviral therapy and responded completely but died 2 months later of an opportunistic infection. We conclude that patients with low-grade B-cell neoplasms treated with fludarabine, possibly in combination with other immune suppressive agents, may subsequently develop EBV-BLPDs that morphologically resemble other iatrogenic immunodeficiency-associated BLPDs. Most are clonally distinct from the underlying low-grade B-cell neoplasm. A subset of these lesions may regress without systemic therapy.     

Three-year prospective study of developmental dysplasia of the hip at birth: should all dislocated or dislocatable hips be treated?

This article presents a 3-year prospective study that includes 103 consecutive patients (137 hips) diagnosed with developmental dysplasia of the hip (DDH) at birth. Treatment was started after 2 weeks only if the hips had not stabilized spontaneously. Sonographic studies were first used when clinical stability was confirmed to ensure a true concentric hip reduction. The authors conclude that most patients with DDH at birth (73.8%) do not need treatment at that time, presenting with normal hips at the end of follow-up. When instability was still present after 2 weeks and a splint was applied (26.2%), there were no significant hip differences when compared with a control group of 50 patients (69 hips) who underwent treatment in the first days of life. With this approach, the authors could safely reduce the number of patients to be treated, the amount of sonographic studies, and consequently the final cost of the whole treatment.     

Elderly patients on chronic hemodialysis: Effect of the secondary hyperparathyroidism on the hemoglobin level

In patients on chronic hemodialysis (CHD)hyperparathyroidism (HPTH) is associated withanemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (meanage 74.8 y, mean time on CHD = 50.5 mos); theywere divided into two groups: I (n = 31) – PTH> 250 pg/mL and II (n = 55) – PTH < 250 pg/mL.All these patients had been on CHD for> 6 mos. No differences were found betweengroups in respect to age, sex distribution andtime on CHD. The levels of creatinine, BUN, Ca,Al, Fe, albumin and ferritin were similar.Group I had a higher P level (5.4 vs 4.3 mg/dL,p = 0.001) and Ca x P (53.5 vs 43.7, p =0.009). Also the Hct (31 vs 33.5%, p = 0.008)and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values werelower in Group I. The EPO dose (88 vs 85 U/kg/week,p = ns) was similar in the two groups.Our data showed that elderly patients with HPTHhave lower Hct and Hb levels than do youngerpatients on a similar EPO dose. We believethese patients will need a more aggressivetherapy with calcitriol.     

Acute rejection in the elderly recipient: Influence of age in the outcome of kidney transplantation

Since the immune response in older recipientsis weaker they should be less likely to rejecta transplanted organ and should need lessaggressive immunosuppressive treatment. Our aimwas to record the incidence and severity ofepisodes of acute rejection (AR), estimate theinfluence of these events on graft survival ofelderly recipients (60) and to comparethese with that in younger ones.We performed 363 kidney transplants between1/94 and 12/98, and recorded clinical andimmunological data, incidence-severity of ARand cause of graft loss. Patients were dividedinto two groups, according to the age attransplantation: A (<60, n = 281/77.4%) and B( 60, n = 82/22.6%). The percentage ofaging recipients and mean age of donors andrecipients increased throughout the period.Although the incidence of ATN was higher in theolder group (29% vs.19%, p < 0.0001) thenumber of graft biopsies was equal in bothgroups. The incidence of AR was similar, 33.4%vs. 26.8%, pNS. The number of AR episodes perpatient was 0.44 and 0.41 respectively. Theseverity of AR was: Banff grade I: A (40.3%)/B (45.7%) pNS; grade II: A (44.1%)/B(48.57) pNS; grade III: A (15.5%)/B (5.7%)pNS. Younger recipients presented a higherlevel of panel-reactive antibodies (PRA) (4.3%vs. 2.07%, p = 0.01). One-year patient survivalwas 96%/91% (p<0.05) and graft survivalwas 81%/78% (pNS) respectively.The age of recipient does not seem to haveinfluenced the incidence-severity of AR or thegraft survival. Thus immunosuppression shouldbe individualised for each patient and shouldnot depend on the age at transplantation.     

Effect of internal biliary drainage on plasma levels of endotoxin,cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.     

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.     

Phacoemulsification in eyes with functioning filtering blebs: a prospective study

OBJECTIVE: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) control in eyes with a previous functioning filtering bleb and no glaucoma medication. DESIGN: Prospective, nonrandomized comparative (self-controlled) trial. PARTICIPANTS: Forty-seven patients (49 eyes) who underwent phacoemulsification after successful trabeculectomy, with at least 12 months of follow-up. INTERVENTION: Clear corneal phacoemulsification and implantation of a foldable intraocular lens in eyes that underwent a previous successful trabeculectomy. The time between both procedures was always greater than 1 year. MAIN OUTCOME MEASURES: Preoperative and postoperative IOP, the number of glaucoma medications, bleb appearance, and visual acuity were recorded at each follow-up examination. Success was defined as no need for glaucoma medications, bleb needling, or further glaucoma surgery for IOP control after phacoemulsification. Preoperative and intraoperative factors were evaluated for an association with postoperative failure using Kaplan-Meier survival analysis. RESULTS: The mean (+/- standard deviation) IOP before phacoemulsification was 12.24 (+/- 4.68) mmHg, and it increased 3.94, 3.76, 1.39, 2.04, and 1.57 mmHg on the first postoperative day, after 1, 6, and 12 months, and at the last visit, respectively. At each interval, the mean IOP was significantly higher than the preoperative value (P = 0.000, 0.000, 0.049, 0.01, and 0.01, respectively). Nevertheless, the mean IOP after phacoemulsification was always lower than before trabeculectomy (P = 0.000). At the last visit, glaucoma medication was required in 17 eyes (34.7%). The success rates after phacoemulsification were 83.6%, 68.2%, and 55.7% at 6 months and 1 and 2 years, respectively (Kaplan-Meier survival analysis). The number of glaucoma medications used increased at all follow-up visits (P < 0.005). Bleb size decreased after phacoemulsification (P = 0.000). An IOP before phacoemulsification of greater than 10 mmHg was associated with postoperative failure (P = 0.002). Similarly, bleb failure and the need for glaucoma medication were associated with higher IOPs before phacoemulsification. CONCLUSIONS: Phacoemulsification significantly increased IOP and the number of glaucoma medications in eyes with preexisting functioning filtering blebs. Eyes with higher IOPs before phacoemulsification had worsened postoperative IOP control and bleb failure.     

Proliferative vitreoretinopathy: risk factors and pathobiology

Proliferative vitreoretinopathy (PVR) is still a major cause of failure of retinal detachment surgery. Despite a dramatic increase in our pathobiologic knowledge of PVR during the last 10 years, little of this information has been used to modify the surgical management of the disease, and, thus, the anatomic and functional results are still unsatisfactory. Collaborative research involving clinicians and basic researchers must be encouraged. PVR must be considered a multifactorial disease caused by interaction of several cells and intra- and extraocular factors. Therefore, therapeutic options based on the inhibition of one factor or phenomenon may be regarded with scepticism. To prevent PVR, it is necessary to determine the factors involved in its development, and because of its relatively small prevalence, large, prospective, multicenter studies seem necessary. In addition, clinical research must not be underestimated. PVR affects both sides of the retina and the retina itself, a point to which little attention has been paid and that is critical for surgical results. Therefore, a new classification that provides information about clinical relevance, such as the evolutionary stages of the disease (biologic activity) and the degree of surgical difficulty (location of the fibrotic process), seems necessary.