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Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma.

The most frequent genetic aberrations in multiple myeloma (MM) are 13q deletions and translocations involving the immunoglobulin heavy chain gene (IGH). There have been no reports on the cytogenetic abnormalities found in Korean patients with MM. We investigated the actual prevalence and prognostic value of cytogenetic changes using fluorescence in situ hybridization (FISH). FISH studies with 12 different specific probes for the regions containing the genes or chromosome regions (13q, 1q, IGH, p53, MLL, p16, CEP 7, CEP 11, and CEP 12) were performed in 128 patients. The most frequent change found was 13q deletion (48%), followed by trisomy 1q (45%), IGH translocation (37%), and trisomy 11 (26%). Among the three different probes used to detect 13q deletion, D13S25 (48/58) was the most sensitive probe compared to RB (43/58) and D13S319 (39/58). Among the patients showing one or more changes by FISH, 75% (82/110) had a 13q deletion, a trisomy 1q, or an IGH translocation. Azotemia, anemia, thrombocytopenia, intramedullary plasmacytosis, and stage were significantly associated with the 13q deletion; serum beta(2)-microglobulin, thrombocytopenia, and intramedullary plasmacytosis were also related to trisomy 1q. The pattern of molecular cytogenetic changes in Korean patients with MM is somewhat different from what has been observed in reported Caucasian populations: 37 versus 50-70% with regard to the IGH translocation. The prevalence of the 13q deletion was similar in Korean and Caucasian populations, 48 versus 30-50%. We suggest that the detection of at least these three genetic changes, 13q- trisomy 1q, and an IGH rearrangement, would be helpful for follow-up of Korean patients with MM.

Adult↗

Hydrometra in a ferret-case report.

A desexed female ferret was presented with bilateral alopecic changes. Clinical examination revealed generalized alopecia and abdominal distension. A polycystic mass was found behind the right kidney, and the whole abdomen was filled with a large turgid mass. Radiography and ultrasonography confirmed the presumptive diagnosis of a hydrometra. Hematology and serum biochemistry showed regenerative anemia with light azotemia. Laparotomy showed the presence of a neoplastic mass at the location of the right ovary, a massive enlargement of the uterus filled with a clear fluid, and a subcapsular cyst on the left kidney. After surgery, histopathologic examination of the tissues diagnosed a leiomyoma of the right ovary with hyperplasia of the uterine wall.

Alopecia↗

Management of ureteral obstruction.

The most common cause of ureteral obstruction in dogs and cats is ureteral calculi. Common clinical signs associated with ureteral obstruction include abnormalities in urination, persistent urinary tract infection, abdominal pain, vomiting, anorexia, weight loss,and depression or lethargy. Medical management of ureteral obstruction includes fluid diuresis, muscle relaxants, and treatment of azotemia using nephrostomy tubes or hemodialysis. Surgical techniques used to restore patency to the ureter include ureterotomy,partial ureterectomy and ureteroneocystostomy, and ureteral resection and anastomosis. Lithotripsy has been used in dogs to remove ureteral calculi. Renal function can be preserved if complete ureteral obstruction is relieved within several days of onset.

Animals↗

Early detection of renal damage and disease in dogs and cats.

Renal damage and disease can be caused by acute or chronic insults to the kidney. Acute renal damage often results from ischemic or toxic insults and usually affects the tubular portion of the nephron. In contrast, chronic renal disease can be caused by diseases and/or disorders that affect any portion of the nephron, including its blood supply and supporting interstitium. Early detection of acute renal disease facilitates appropriate intervention that can arrest or at least attenuate tubular cell damage and the development of established acute renal failure. Similarly,early detection of chronic renal disease, before the onset of renal azotemia and chronic renal failure, should facilitate appropriate intervention that stabilizes renal function or at least slows its progressive decline.

Acute Disease↗

Postoperative naproxen after coronary artery bypass surgery: a double-blind randomized controlled trial.

OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used after coronary artery bypass surgery (CABG), yet their effects have seldom been evaluated in randomized controlled settings. The aim of this study was to examine the efficacy and safety of a commonly used NSAID, naproxen. We hypothesized that naproxen would reduce postoperative pain following CABG without increasing complications. METHODS: Patients (N=98) undergoing primary CABG were randomized to receive naproxen (500 mg q12hX5 doses via suppository started 1h after operation, followed by oral 250 mg q8hX6 doses) or placebo. Standard analgesic and anti-emetic regimens were available to both patient groups. Interventions were double-blinded. Primary end-points were postoperative pain measured before and after chest physiotherapy by visual analog scale and pulmonary slow vital capacity (SVC). RESULTS: Baseline characteristics were equivalent between the two groups. Over the first 4 postoperative days, naproxen decreased pain by 47+/-17% on average before chest physiotherapy (P=0.034), and 44+/-13% after chest physiotherapy (P=0.0092). Patients who received naproxen also had better preservation of SVC over the first 4 postoperative days (mean loss of SVC from baseline: 2.1+/-0.1 vs. 2.5+/-0.1l, naproxen vs. placebo, P=0.0032). This was concomitant with a lower white blood cell count observed in naproxen patients (9.2+/-0.3 vs. 12.7+/-1.5x10(9)/l, naproxen vs. placebo, P=0.03). Patients who received naproxen had more chest tube drainage after 4h postoperatively, but there was no difference in the incidence or amount of transfusions. There was no difference in medication use, length of stay, or in the incidence of atrial fibrillation, azotemia, and other complications. CONCLUSIONS: Naproxen is an effective and low-cost adjunct for optimization of pain control and lung recovery after CABG. Its use may result in increased chest tube drainage, but no apparent increase in other complications.

Analysis of Variance↗

[Patterns of nephrology referral and predialysis management of patients with chronic kidney disease].

INTRODUCTION: Numerous studies showed that late referral (LR) to a nephrologist of patients with chronic kidney disease stated by a simple quantitative criterium (initiation of renal replacement therapy (RRT) within 3 or 4 months of referral to a nephrologist, independantly from the quality of care) is associated with worse survival rate, limited to the first 3 months following the initiation of RRT. We wanted to test a criterium of LR definition supposing a more important "dose of nephrological care", to try to understand the reasons of this early death. METHODS: One hundred and thirty-eight patients receiving their first RRT in 1999 and 2000 in Valenciennes (France) were enrolled in this study. Two LR definitions were used: a qualitative criterium C1 (whether the patient was under an uninterrumpted nephrological pre-dialysis care - independantly from the date of the nephrological referral - or not) and a more simple quantitative criterium C2 (initiation of RRT within 3 months of referral to a nephrologist). Comorbidity was assessed by Charlson's score. The analysis concerned the respective influence of C1 and C2 on the clinical and biological effects of chronical azotemia, on the circumstances at first RRT (emergency first dialysis, pulmonary edema, type of vascular access), and on survival rates (Kaplan-Meier's analysis). RESULTS: LR rates are 23% according to C1 and 20% according to C2. Comorbidity is similar in the different groups. Whatever the definition criterium, LR is associated to a lower hemoglobin and albumin, a more severe acidosis, a longer duration of first hospitalization, and higher rate of emergency first dialysis and use of central temporary catheter. The survival rates at 2 years following the first RRT of lately referred patients are 53% according to C1 (vs 86% for early referred patients, P<0,001) and 56% according to C2 (vs 84%, P<0,05). For both, early death (within the first 3 months) explained the observed differences of survival rates. CONCLUSION: In this study, early death of lately referred patients seems to be independant from the criterium of definition of LR. Elements of explanation are suggested, and can lead to further prospective studies.

Humans↗

Evaluation of renal and hepatic functions in dogs naturally infected by visceral leishmaniasis submitted to treatment with meglumine antimoniate.

The present study aimed to evaluate the renal and hepatic responses in eight dogs with visceral leishmaniasis submitted to treatment with meglumine antimoniate and to verify the occurrence of possible side effects. Urinalysis, hepatic and renal function tests were carried out in all animals at up to seven moments. After the end of a six-month observation period, all dogs were euthanized. Before the beginning of the experiment urinary and biochemical alterations were observed in four dogs due to the changes caused by the parasite itself. These alterations included the presence of renal cells, cylindruria, proteinuria, azotemia, hyperproteinemia and hypoalbuminemia. One dog died on the third day after treatment because an aggravation of the clinical picture, probably due to the medication. During the course of the study, an increase in hepatic enzymes was verified in two animals. Sixty days after the beginning of the treatment four dogs showed remission of clinical signs. The other three were asymptomatic with persistent biochemical alterations. From these, two presented recurrence of clinical signs about 150 days after the beginning of the treatment while in the other, hyperproteinemia persisted. Meglumine antimoniate was not efficient to treat dogs with severe renal dysfunction and the side effects observed were pain at the site of injection and the probable transient hepatotoxicity, evidenced by biochemical examinations, but without the presence of clinical signs.

Animals↗

Brown spider dermonecrotic toxin directly induces nephrotoxicity.

Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from culture substratum. In addition, dermonecrotic toxin treatment of MDCK cells changed their viability evaluated by XTT and Neutral-Red Uptake methodologies. The present results point to brown spider dermonecrotic toxin cytotoxicity upon renal structures in vivo and renal cells in vitro and provide experimental evidence that this brown spider toxin is directly involved in nephrotoxicity evoked during Loxosceles spider venom accidents.

Amino Acid Sequence↗

Heat shock proteins and acquired resistance to uranium nephrotoxicity.

Previous studies have demonstrated that prior exposures to uranium can produce acquired resistance to uranium nephrotoxicity. In this study, the potential role for heat shock proteins (Hsps) in acquired resistance to uranium nephrotoxicity was explored. Pretreatment of male Sprague-Dawley rats with a conditioning dose of uranyl acetate (5 mg/kg, i.p.) was found to diminish the severity of proximal convoluted tubule necrosis and azotemia produced by a subsequent, higher uranyl acetate dose (10 mg/kg, i.p., 10 days after the conditioning dose). Kidney homogenates from rats euthanized at the end of the conditioning period were found to contain elevated levels of Hsp25, Hsp32, and Hsp70i, but not Hsc70. Immunochemical staining of renal sections for Hsp25 and Hsp70i revealed that these proteins were prominently expressed in tubular epithelial cells in uranyl acetate pretreated animals. Morphological characteristics and staining for proliferating cell nuclear antigen (PCNA) indicated that the cells expressing high levels of Hsps were regenerating. In RK3E and LLC-PK1 renal epithelial cells in culture, Hsp induction by thermal pretreatment did not afford protection from uranyl acetate cytotoxicity. Further, treatment of RK3E and LLC-PK1 cells with uranyl acetate did not result in induction of Hsps, as occurs with other nephrotoxic heavy metals. These observations suggest that while stress proteins are elevated in acquired resistance to uranyl acetate in vivo, they are not responsible for diminished uranium nephrotoxicity but are an epiphenomenon of tubular epithelial regeneration.

Animals↗

Analysis of allograft biopsy specimens in renal transplants with proteinuria: is proteinuria a culprit of graft loss?

It has been proposed that proteinuria occurring after renal transplantation may be not only a marker but also a culprit of allograft dysfunction. We retrospectively analyzed the data from 55 patients who underwent transplant renal biopsy for proteinuria and/or azotemia occurring beyond 1 year after transplantation. Proteinuria was considered as significant when > or = 30 mg/dL, and the results of transplant biopsy were categorized according to the Banff 97 classification. Logistic regression was used to estimate odds ratios (OR) for graft loss associated with proteinuria and transplant pathology. The patients were followed for 86.0 +/- 32.8 months after transplantation, and transplant biopsy was performed at 54.1 +/- 31.0 months. Proteinuria at 1 year after transplantation noted in 29.1% of patients was not significantly associated with graft loss (OR = 1.94, 95% CI from 0.59 to 6.41). In addition, proteinuria at the time of transplant biopsy was not significantly associated with graft loss. Chronic allograft nephropathy was the most frequent transplant pathology. Only glomerulonephritis was significantly associated with proteinuria at the time of the transplant biopsy. On the other hand, graft loss was significantly associated with the presence of proteinuria both at 1 year after transplant biopsy and at the final follow-up. These results suggest that posttransplantation proteinuria is an important marker of graft dysfunction, but is not predictive of graft loss in biopsy-proven cases. Appropriate management guided by the results of a transplant biopsy may improve the outcome.

Biopsy↗

Initial single-center experience with sirolimus after lung transplantation.

BACKGROUND: Standard immunosuppression after lung transplantation includes calcineurin inhibitors, mycophenolate mofetil, and steroids. Long-term survivors of lung transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin inhibitors. Sirolimus has been increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity, which could be used in selected patients. METHODS: We prospectively administered sirolimus as an alternative to calcineurin inhibitors in 10 lung transplantation recipients with persistent drug nephrotoxicity. They were switched from tacrolimus to sirolimus. Four patients also had bronchiolitis obliterans syndrome. The conversion scheme consisted of an immediate stop of tacrolimus and an 6 to 8-mg loading dose of sirolimus, followed by 4 mg/d. After 5 days, the sirolimus dose was adjusted to maintain trough levels between 12 and 18 ng/mL or 6 and 12 ng/mL for combined sirolimus and tacrolimus. Patients were monitored for renal and graft function as well as clinical status. RESULTS: A significant decrease in creatinine was observed after 1 week of treatment (P = .011). Azotemia decreased after 1 month, remaining stable (P < .01). Pulmonary function tests did not show significant modification from before sirolimus, inception in patients with or without bronchiolitis obliterans syndrome. There were seven infections. One patient died of complications related to bronchiolitis obliterans. CONCLUSION: Sirolimus was a useful alternative immunosuppressant, allowing significant tacrolimus withdrawal in transplant recipients with renal impairment. Sirolimus administration allowed recovery of renal function with low morbidity; it was useful for rescue of chronic renal impairment after lung transplantation.

Bronchiolitis Obliterans↗

Cardiac arrhythmias associated with piroplasmosis in the horse: a case report.

Cardiac dysfunction is a rare complication of babesiosis in domestic animals. The horse in this report showed clinical signs of anorexia, depression, fever, icterus and brown urine, and laboratory results (monocytosis, thrombocytopenia, azotemia, hyperbilirubinemia and bilirubinuria) indicated sub-acute piroplasmosis. Furthermore, junctional and polymorphic ventricular premature complexes and tachycardia associated with increased serum cardiac troponin I and myocardial-bound creatine kinase concentration were found. The diagnosis of piroplasmosis was confirmed by serology. Specific and supportive therapy for babesiosis allowed remission of clinical signs and laboratory profile abnormalities, including those of myocardial involvement. Myocardial damage associated with cardiac arrhythmia may be a complication of equine babesiosis as already demonstrated in other species.

Animals↗

Acute renal failure resulting from huge inguinal bladder hernia.

We report a case of a huge inguinal/scrotal bladder hernia presenting as acute renal failure. A 66-year-old man with a large scrotal mass presented with metabolic acidosis and azotemia and was admitted to the intensive care unit. Computed tomography displayed the bladder completely herniated into the scrotum and bilateral hydronephrosis. After stabilization and percutaneous nephrostomy placement, the patient's creatinine markedly improved, and the hernia was repaired. Bilateral ureteral obstruction from a bladder hernia is a very rare event. Computed tomography is rapid and helpful in this situation. Hernia repair can safely be performed after nephrostomy drainage.

Acute Kidney Injury↗

Piroplasma infection in dogs in northern Spain.

Babesiosis is a world-wide zoonosis caused by tick-borne hematozoan parasites of the genus Babesia. Canine Babesidae have historically been classified as "large Babesia" (Babesia canis) and "small Babesia" (Babesia gibsoni) based on the size of their intraerythrocytic forms. Genetic sequencing technology using the polymerase chain reaction (PCR) has allowed further subdivision. B. gibsoni has three strains: "Asia", "California" and a recently identified small babesial-like parasite, Theileria annae. This newly recognised piroplasm appears to be hyperendemic in northwest Spain. In order to provide some insight into the situation, all the cases diagnosed in our laboratory (NW of Spain) during 2003 were evaluated. Our study (62 samples) shows the existence of a piroplasm morphologically different from B. canis and similar to B. gibsoni, which is genetically related to T. annae. Severe regenerative anemia and thrombocytopenia are almost constant characteristics of infection with T. annae in dogs. In many cases azotemia is found. Abnormally high serum concentrations of urea and creatinin, together with elevated concentrations of inorganic phosphorus, hypoalbuminemia, hypercholesterolemia, proteinuria, high protein/creatinin and presence of hyaline and granular casts in the microscopic examination of urine sediment suggest a glomerular component to the disease. We conclude that observational research and clinical trials should be conducted in order to improve our understanding of this emerging disease in order to provide some insight into the best therapeutic practices.

Animals↗

Cisplatin as initial chemotherapy in ovarian carcinosarcomas: a Gynecologic Oncology Group study.

OBJECTIVES: Carcinosarcomas of the ovary are rare; hence, although most patients recur after surgical resection or have metastatic disease at the time of diagnosis, only anecdotal information is available concerning the activity of cytotoxic drugs against these lesions. The Gynecologic Oncology Group (GOG) initiated a concerted effort to study cytotoxic therapy for these cancers in 1976. This report presents data on cisplatin, the first of the agents to be studied in this disease. METHODS: One hundred thirty-six eligible patients with ovarian carcinosarcoma received cisplatin (50 mg/m(2)) every 3 weeks until disease progression or unacceptable toxicity. RESULTS: Among 44 patients evaluable for response, one complete (2%) and eight partial (18%) responses resulted. An additional 10 (23%) patients exhibited stable disease, while 25 (57%) had increasing disease. Median progression-free survival in 130 patients evaluable for this endpoint was 5.2 months. Median survival in the same 130 patients was 11.7 months. Adverse effects >/=grade 2 among the 132 patients evaluable for toxicity included leukopenia (14%), neutropenia (17%), thrombocytopenia (2%), anemia (10%), nausea and vomiting (40%), azotemia (3%), neurotoxicity (4%), fever (2%), and tinnitus (1%). CONCLUSIONS: These data provide the first objective evidence that cisplatin is active as an initial therapy for patients who have carcinosarcoma of the ovary. The overall response rate (20%) is similar to that seen in carcinosarcomas of the uterus.

Adult↗

Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study.

OBJECTIVE: Following a reported 23% response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) + MAP + sargramostim, the Gynecologic Oncology Group (GOG) conducted a phase II trial of DMAP + sargramostim in patients with advanced uterine leiomyosarcoma. METHODS: Eligibility required measurable disease, a GOG performance score of 0-2, and recovery from surgery/radiotherapy. Treatment consisted of sargramostim 250 microg/m2 SC q 12 h days -6 through -3, followed by D 750 mg/m2 IV over 2 h, M 6 mg/m2 IV, A 40 mg/m2 IV and P 60 mg/m2 IV over 2 h on day 1, followed by sargramostim 250 microg/m2 SC days 2-15. Cycles were repeated q 28 days (if ANC > or = 1500/microl and platelets > or = 100,000/microl) until disease progression or toxicity prevented further therapy. Doses were to be reduced by 20% for grade 4 neutropenia >7 days or any grade 4 thrombocytopenia and by 10% for a 1- to 2-week treatment delay for myelosuppression. RESULTS: One of 19 patients who entered the study was ineligible. Eighteen patients received a median of 3.5 cycles (range: 1-6 cycles) of therapy. The overall RR was 27.8% (5.6% complete and 22.2% partial responses). Percent of patients with grade 3 or 4 toxicities included 78% neutropenia, 94% thrombocytopenia, 61% anemia, 44% GI, 28% infection, and 17% azotemia. CONCLUSIONS: DMAP + sargramostim produced a 27.8% RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual.

Adult↗

Radiologic diagnosis of renovascular hypertension and percutaneous transluminal renal angioplasty.

Percutaneous transluminal renal angioplasty (PTRA) is a low risk, cost-effective procedure with a high degree of technical and therapeutic success in most categories of renovascular hypertension (RVH) when performed at experienced centers. The role of radiology in screening and diagnosis is discussed with special attention to renal vein sampling for renin assay (RVR) and digital subtraction angiography (DSA). The results of PTRA are compared with surgery. At New York Hospital, PTRA is the procedure of first choice in fibromuscular dysplasia, unilateral nonostial atheroma, arteritis, renal transplantation, and pediatrics. In patients with bilateral and ostial atherosclerotic disease and/or azotemia, the choice between surgery or PTRA depends on the surgical risk category of the patient.

Angioplasty, Balloon↗

Radionuclide renography: a personal approach.

Recent advances have increased the value of radionuclide renography in evaluating the patient with suspected disease of the genitourinary tract. The use of the consensus process to help standardize procedures and recommend interpretative criteria provides guidance for the nuclear medicine practitioner, serves as a basis to improve the standard of practice, and facilitates pooling of data from different centers. This review draws on the consensus criteria to present a personal approach to radionuclide renography with a particular emphasis on diuresis renography and the detection of renovascular hypertension. Patients are encouraged to come well hydrated and void immediately prior to the study. Our standard radiopharmaceutical is 99mTc mercaptoacetyltriglycine (MAG3). Routine quantitative indices include a MAG3 clearance, whole kidney and cortical (parenchymal) regions of interest, measurements of relative uptake, time to peak height (Tmax), 20 min/max count ratio, residual urine volume and a T(1/2) in patients undergoing diuresis renography. A 1-minute image of the injection site is obtained at the conclusion of the study to check for infiltration because infiltration can invalidate a plasma sample clearance and alter the renogram curve. A postvoid image of the kidneys and bladder is obtained to calculate residual urine volume and to better evaluate drainage from the collecting system. In patients undergoing diuresis renography, the T(1/2) is calculated using a region of interest around the activity in the dilated collecting system. A prolonged T(1/2), however, should never be the sole criterion for diagnosing the presence of obstruction; the T(1/2) must be interpreted in the context of the sequential images, total and individual kidney function, other quantitative indices and available diagnostic studies. The goal of ACE inhibitor renography is to detect renovascular hypertension, not renal artery stenosis. Patients with a positive study have a high probability of cure or amelioration of the hypertension following revascularization. In patients with azotemia or in patients with a small, poorly functioning kidney, the test result is often indeterminate (intermediate probability) with an abnormal baseline study that does not change following ACE inhibition. In patients with normal renal function, the test is highly accurate. To avoid unrealistic expectations on the part of the referring physician, it is often helpful to explain the likely differences in test results in these two-patient populations prior to the study.

Aged↗