Measurements of echocardiographic indices and biomarkers of kidney injury in dogs with chronic kidney disease.

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRDK), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRDK in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored. Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRDK was suggested by the association between LVPWDN and survival.

Septicemia in pediatric oncology patients: the significance of viridans streptococcal infections.

One hundred nine consecutive episodes of septicemia were retrospectively evaluated in 61 children with malignancy. In addition, the records of all pediatric oncology patients who received high-dose cytarabine (HDAC) chemotherapy were reviewed. Gram-positive organisms accounted for 82.6% of the septicemic episodes. In the total group, coagulase-negative staphylococci and viridans streptococci accounted for 35.8% and 28.4% of the episodes, respectively. In granulocytopenic patients, viridans streptococci were the most common pathogens (36.8%). In the subset of patients who received HDAC, 62.5% of the septicemic episodes were caused by viridans streptococci. Pulmonary complications developed in nine (29%) of the total cases of viridans streptococcal sepsis, whereas these complications occurred in only eight (10.3%) of the septic episodes caused by other organisms. In patients who had viridans septicemia, prior treatment with HDAC did not increase the incidence of pulmonary complications. In septic children with malignancy, our results demonstrate a high incidence of gram-positive organisms, including viridans streptococci, which were once regarded as culture contaminants.

Timing and magnitude of decline in alpha-fetoprotein levels in treated children with unresectable or metastatic hepatoblastoma are predictors of outcome: a report from the Children's Cancer Group.

PURPOSE: We analyzed data on 31 children with primary unresectable or metastatic hepatoblastoma (HB) to investigate possible prognostic correlations between the serum level of alpha-fetoprotein (AFP), its changes during treatment, and outcome. PATIENTS AND METHODS: Patients were treated according to the Children's Cancer Group (CCG) protocol 823F, which included an initial surgery before eight courses of chemotherapy that consisted of cisplatin immediately followed by a continuous infusion of doxorubicin. Four courses were given before and four after the second surgery. AFP levels were measured before treatment, before and after second surgery, and at the end of treatment. RESULTS: Twenty-four of 31 patients showed a decline of > or = 1 log in AFP levels before second surgery (early responders). By the end of treatment, there were 16 patients, all early responders, without clinical or radiographic evidence of tumor and with normal AFP levels. Fifteen of those 16 had a decline of > or = 2 logs in AFP before second surgery (large early response). Of the 15 patients who failed to respond to treatment, 10 died, among whom only one patient had a large early response. A large early response was the strongest independent predictor of outcome in a univariate and multivariate Cox regression model, and patients with such a response had the best survival (P < .0001). CONCLUSION: For children with unresectable or metastatic HB, early changes in AFP levels are a reliable predictor of outcome and can be used for identification of poor responders to treatment, ie, patients whose AFP level fails to decrease 2 logs before second surgery should be considered for alternative treatment.

Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin chemotherapy: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) undertook a study (CCG-823F) to test the feasibility of administering continuous infusion doxorubicin (CI DOX) and cisplatin (CDDP) in patients with unresectable or incompletely resected hepatoblastoma (HB) or hepatocellular carcinoma (HCC). Chemotherapy consisted of CI DOX 20 mg/m2/d for days 1 to 4 and CDDP 100 mg/m2 on day 1 followed by a 21-day rest period. Second-look surgery was performed after the administration of four chemotherapy courses. Forty-seven (47) assessable patients were entered on study, 33 with HB and 14 with HCC; of these, 34 (26 HB and eight HCC) completed the initial four courses of chemotherapy. Of the 26 HB patients, 25 were evaluated as responding to chemotherapy before the scheduled second-look procedure and were considered surgically resectable at that time. Surgery was performed on 22 patients; three patients refused the second-look surgery. Nine patients had no evidence of residual malignant disease, seven underwent surgical resection of remaining tumor, four were left with microscopic residual disease, one had a partial resection with gross tumor left behind, and one remained unresectable. Nine HCC patients completed four chemotherapy courses. Eight patients achieved a partial remission and second-look surgery was attempted on seven. Only two had all malignant disease removed at the second procedure. Data from 225 courses of chemotherapy were evaluated for toxicity. Neutropenia (absolute granulocyte count less than 500/mL) was observed in 68 courses, and five of these episodes were associated with sepsis. Severe mucositis was documented in 21 courses, and hypomagnesemia (magnesium less than 1.2 mg) was noted in 30 patients. Two patients developed decreased left ventricular shortening fraction, which resolved when chemotherapy was discontinued. In summary, CI DOX plus CDDP is a well-tolerated and effective regimen in inducing surgical resectability in HB patients who are unresectable at diagnosis and significantly improves survival for this group of patients to 66.6%.

Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group.

PURPOSE: Previous studies demonstrated that chemotherapy with either cisplatin, vincristine, and fluorouracil (regimen A) or cisplatin and continuous infusion doxorubicin (regimen B) improved survival in children with hepatoblastoma. The current trial is a randomized comparison of these two regimens. PATIENTS AND METHODS: Patients (N = 182) were enrolled onto study between August 1989 and December 1992. After initial surgery, patients with stage I-unfavorable histology (UH; n = 43), stage II (n = 7), stage III (n = 83), and stage IV (n = 40) hepatoblastoma were randomized to receive regimen A (n = 92) or regimen B (n = 81). Patients with stage I-favorable histology (FH; n = 9) were treated with four cycles of doxorubicin alone. RESULTS: There were no events among patients with stage I-FH disease. Five-year event-free survival (EFS) estimates were 57% (SD = 5%) and 69% (SD = 5%) for patients on regimens A and B, respectively (P =.09) with a relative risk of 1.54 (95% confidence interval, 0.93 to 2.5) for regimen A versus B. Toxicities were more frequent on regimen B. Patients with stage I-UH, stage II, stage III, or stage IV disease had 5-year EFS estimates of 91% (SD = 4%), 100%, 64% (SD = 5%), and 25% (SD = 7%), respectively. Outcome was similar for either regimen within disease stages. At postinduction surgery I, patients with stage III or IV disease who were found to be tumor-free had no events; those who had complete resections achieved a 5-year EFS of 83% (SD = 6%); other patients with stage III or IV disease had worse outcome. CONCLUSION: Treatment outcome was not significantly different between regimen A and regimen B. Excellent outcome was achieved for patients with stage I-UH and stage II hepatoblastoma and for subsets of patients with stage III disease. New treatment strategies are needed for the majority of patients with advanced-stage hepatoblastoma.

Long-term follow-up of a patient transplanted for Hunter's disease type IIB: a case report and literature review.

Unlike most other storage diseases and despite clinical experience, the indications for bone marrow transplantation in Hunter's disease remain controversial. The case of a 14-year-old male with mucopolysaccharidosis type IIB is presented, who received an allograft from his HLA-identical sibling. The donor had been off therapy for acute lymphoblastic leukemia for 3 years. The patient experienced minimal difficulties with his transplant and was fully engrafted by day 42, with no signs of acute or chronic graft-versus-host disease. Now, more than 3 years after BMT, the patient has experienced significant subjective and objective improvement in his disease. The iduronate-2-sulfatase levels in the serum are now approximately 10% of normal control. Urinary glycosaminoglycans were negative. The posttransplant marrow was evaluated for donor-recipient source using VNTR analysis with the polymerase chain reaction (PCR). This showed a PCR-detectable subpopulation of residual patient marrow cells remaining, suggesting a state of stable mixed chimerism. The patient continues to show signs of amelioration of his disease. These results may be of value in determining the proper therapy for a patient with mild Hunter's disease, and may also be pertinent to the future application of recombinant enzyme therapy or gene therapy.

Bone marrow transplantation in the management of childhood cancer.

Bone marrow transplantation has become a curative therapy for selected children with leukemia and offers promise as a treatment for certain childhood solid tumors. Complications such as graft-versus-host disease, interstitial pneumonia, and recurrent malignancy continue to affect many patients. As these are overcome, and as methods for T-cell depletion and marrow purging are developed that extend the scope of bone marrow transplantation, it will become an even more significant therapy for childhood malignancy.

The effect of chemotherapy on hepatoblastoma.

A 15-month-old girl had a case of mixed hepatoblastoma. The unresectable tumor became surgically resectable after treatment with doxorubicin hydrochloride and cisplatin, which was also continued postoperatively. This regimen had a remarkable necrotizing effect on the fetal epithelial component of the hepatoblastoma. The patient's high alpha-fetoprotein level and extreme thrombocytosis, which resolved with treatment, were used as indicators of the disease's activity. An unaffected mesenchymal component and a few microscopic foci of undisturbed embryonal hepatoblastoma were found. The finding of a mature intestinal epithelial island in this case is unique.

Hatching, chemokinesis, and transformation of miracidia of Schistosoma mansoni.

Hatching, chemokinesis, and transformation of miracidia of Schistosoma mansoni were examined with a light microscope equipped with a video recording system. Saline, linearly and reversibly, inhibited miracidial hatching and swimming. Both hatching and swimming were inhibited at 4 C and 12 C and accelerated at 34 C relative to rates at 22 C. Hatching was an explosive event that began with ciliary beating when the egg was placed in artificial pond water (APW) and culminated in the parasite's escape from the shell in 100 to 300 msec. Broken egg shells had sharp, complementary edges. Neither miracidia nor eggs swelled prior to hatching. Accumulation of miracidia in a spot of snail conditioned water (SCW) occurred rapidly due to a 60-75% decrease in the exit rate from the spot, rather than by an increase in the entry rate. The turning rate in SCW increased tenfold and the time spent in the spot was 6 times that of controls. Eserine sulfate inhibited miracidial turning and accumulation in SCW. Parasites accumulated in a spot of serotonin by increasing their rate of turning. Miracidia transformed to sporocysts in either complex media containing serum, RPMI-1640, Hanks' salts or phosphate buffered saline, but not in amino acids or vitamins. Transformation was inhibited when miracidia were incubated with serotonin or when miracidia had not been exposed previously to APW.

Leech therapy in digital replantation.

This article presents a protocol for the perioperative care of patients undergoing digital replantation, which is the most common microsurgical procedure performed today. Venous congestion, a common complication of digital replantation, often has been treated through surgical exploration and creation of arteriovenous anastomosis. Leech therapy, however, is experiencing a resurgence among surgeons as an alternative method for treating venous congestion. This article discusses the anatomical, physiological, and clinical indications and methods of leech therapy in digital replantation.

Characterization of isoelectric point (pI) fractions of soluble egg antigen of Schistosoma japonicum.

The soluble egg antigen of Schistosoma japonicum was fractionated into 20 individual isoelectric point (pI) fractions with different pIs ranging from 1.86-11.40 by isoelectric focusing (IEF). The fractions were tested for humoral and cellular responses, as well as in vitro granuloma formations. The results indicated that the fractions in the acidic region (pI 3.78-5.54) may play an important role in granuloma elicitation in schistosomiasis japonica, and antibodies are also involved in the regulation of granuloma formation especially at the early stage (5 week postinfection).

The multiple hematologic manifestations of neuroblastoma.

The hematologic manifestations of neuroblastoma are numerous and varied. Bone marrow invasion by tumor cells may cause leukoerythroblastic changes or depression of one or more of the cell lines in the peripheral blood; occasionally bone marrow involvement may be so extensive that tumor cells may be released into the peripheral blood and lead to an erroneous diagnosis of leukemia. Anemia in neuroblastoma patients may result not only from bone marrow involvement, but also from bleeding into a tumor mass or from the hemolysis accompanying a consumption coagulopathy. A specific morphologic abnormality, the cogwheel erythrocyte, has been reported in patients with neuroblastoma. Neuroblastoma may also be associated with elevation of the platelet count or a hypercoagulable state. Recognition of these protean hematologic manifestations may facilitate diagnosis in children with atypical presentations of this highly malignant tumor.

Body temperature as a conditional response measure for pavlovian fear conditioning.

On six days rats were exposed to each of two contexts. They received an electric shock in one context and nothing in the other. Rats were tested later in each environment without shock. The rats froze and defecated more often in the shock-paired environment; they also exhibited a significantly larger elevation in rectal temperature in that environment. The rats discriminated between each context, and we suggest that the elevation in temperature is the consequence of associative learning. Thus, body temperature can be used as a conditional response measure in Pavlovian fear conditioning experiments that use footshock as the unconditional stimulus.

Acute pancreatitis in association with cytosine arabinoside therapy.

This paper reports the association of acute pancreatitis coincident with cytosine arabinoside (Ara-c) therapy in a single patient on at least two occasions. The patient had previously received L-asparaginase, but the last dose had been given 4 months prior to the onset of pancreatitis. A literature review provided two more cases of pancreatitis associated with Ara-c therapy in patients previously treated with L-asparaginase. In view of th extreme rarity of pancreatitis in patients receiving Ara-c, the possibility arises that prior treatment with L-asparaginase may predispose the pancreas to this complication.

The cell-mediated response to schistosomal antigens at the clonal level. III. Identification of soluble egg antigens recognized by cloned specific granulomagenic murine CD4+ Th1-type lymphocytes.

Granulomatous inflammation in schistosomiasis is a consequence of T cell-mediated hypersensitivity to parasite egg Ag. In the present study we used three consecutive independent chromatographic procedures to fractionate and identify the soluble egg Ag recognized by schistosome-specific, cloned, murine, CD4+ Th1-type lymphocytes, which had been shown previously to be capable of mediating granuloma formation in vivo when adoptively transferred to normal syngeneic hosts challenged with an i.v. injection of eggs. The stimulatory activity resided in two acidic egg molecules, with apparent molecular masses of 64 to 68 kDa and 38 to 42 kDa, each of which ran as a single band on SDS-PAGE after purification. Fast performance liquid chromatography and SDS-PAGE performed under reducing conditions suggested that the two molecules are related and that the 38- to 42-kDa molecule is a subunit of the 64- to 68-kDa molecule. Polyclonal lymphoid cells from schistosome-infected mice were similarly stimulated by the purified 64- to 68-kDa and 38- to 42-kDa molecules, implying that these are sensitizing Ag in the natural disease.

Heterogeneity of antigen-specific CD4+ T cell clones from a patient with Schistosomiasis mansoni.

Two subsets of differentiated murine helper T cells, Th1 and Th2, based on secretion products in response to antigen have been described (Cher & Mosmann 1987, Coffman et al. 1988, Lopez et al. 1988, Paliard et al. 1988, Patel et al. 1988, Mosmann & Coffman 1989). To analyse immunological function of antigen-specific CD4+T cells in human schistosomiasis, we produced schistosomal egg antigen-specific T cell clones from a former patient. We identified four different types of CD4+ T cell clones by analysis of cytokine production. Two of the four types of the clones corresponded to murine Th1 or Th2 subsets; a third type was of the Th0 subset (Th1 + 2) and a fourth type produced IL-5 dissociated from IL-4. Analysis of the antigen(s) recognized by these T cell clones showed that all of the clones proliferated in response to soluble egg antigen(s) (SEA) found within a pl fraction whose pH was 5.2. T cell Western blot analysis of the stimulatory pl fraction demonstrated that the apparent Mr of the relevant antigens recognized by the clones were 38 kDa for the Th2 homologue, and 45-55 kDa for the Th1 homologue.