Primary lower urinary tract reconstruction for nonfunctioning renal moieties associated with obstructing ureteroceles

PURPOSE: Upper pole heminephrectomy is the conventional treatment for severely compromised nonfunctioning renal units associated with ureteroceles due to the potential morbidity of leaving a nonfunctioning renal moiety in place. This approach often fails to address the pathological anatomical defect present at the bladder level, and during long-term followup the majority of patients require subsequent lower tract surgery due to persistent ureterocele, new or persistent vesicoureteral reflux, or recurrent infections. We determined the success of primary lower urinary tract reconstruction for nonfunctioning renal moieties and the morbidity associated with leaving nonfunctioning renal units in situ. MATERIALS AND METHODS: We present the collective experience of 2 institutions using definitive lower urinary tract reconstruction without upper tract ablative surgery in 16 patients with duplex collecting systems and an associated nonfunctioning renal moiety due to obstructing ureteroceles. RESULTS: At a mean followup of 62 months upper tract dilatation was decreased or completely resolved in all patients, no loss of renal function was present and 15 of 16 patients (94%) had no evidence of persistent reflux. Postoperative complications in the form of a urinary tract infection occurred in 2 of 16 patients (13%). No patient was febrile. No patient had development of hypertension, proteinuria or tumor during followup. CONCLUSIONS: We believe that primary, single stage, lower urinary tract reconstruction in children with severely compromised or nonfunctioning renal moieties damaged by ureteroceles is superior to upper urinary tract ablative surgery, successfully correcting the obstructive or refluxing pathology with minimal morbidity and risk during long-term followup.     

Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder

OBJECTIVE: To assess the potential use of bone marrow stromal cell (BMSC)-seeded biodegradable scaffold for bladder regeneration in a canine model, by characterizing BMSCs and comparing them to bladder smooth muscle cells (SMCs) by immunohistochemistry, growth capability, and contractility. MATERIALS AND METHODS: Bone marrow was taken by direct needle aspiration from the femurs of five beagle dogs for the in vitro study. Mononuclear cells were isolated by Ficoll-Paque density gradient centrifugation and cultivated in medium 199 with 10% fetal bovine serum. BMSCs were characterized by cell proliferation, in vitro contractility, immunohistochemical analysis, and the growth pattern on small intestinal submucosa (SIS) scaffolds compared to bladder SMC cultures from the same dogs. Another six dogs had a hemicystectomy and bladder augmentation with BMSC-seeded (two), bladder cells including urothelial cells plus SMC-seeded SIS (two) and unseeded SIS scaffolds (two). The six dogs were followed for 10 weeks after augmentation. RESULTS: In vitro BMSCs had a significant contractile response to calcium-ionophore, with a mean (sem) 36 (2)%, relative contraction (P < 0.01), which was similar to bladder SMCs but markedly different from fibroblasts. BMSCs also expressed alpha-smooth muscle actin by immunohistochemical staining and Western blotting, but did not express desmin or myosin. In vivo, both BMSC-seeded and bladder cell-seeded SIS grafts had solid smooth-muscle bundle formation throughout the graft. CONCLUSIONS: BMSCs had a similar cell proliferation, histological appearance and contractile phenotype as primary cultured bladder SMCs. SIS supported three-dimensional growth of BMSCs in vitro, and BMSC-seeded SIS scaffold promoted bladder regeneration in a canine model. BMSCs may serve as an alternative cell source in urological tissue engineering.     

Captopril mediated decrease of aortic regurgitation.

The effect of captopril mediated afterload reduction on aortic regurgitation was investigated in 10 patients. Regurgitation was quantitated by means of the regurgitation fraction and the relation of regurgitant volume to end diastolic volume. These variables were derived from gated radionuclide ventriculography. After captopril treatment the blood concentration of angiotensin I rose whereas that of angiotensin II fell significantly. The conversion of angiotensin I to II was reduced to about 50% of the control value. Whereas blood pressure and heart rate did not change significantly, the regurgitation fraction and the regurgitant volume, normalised to end diastolic volume, were significantly reduced by captopril treatment. The ejection fraction remained essentially unchanged. These findings suggest that captopril reduces aortic regurgitation by reducing afterload.     

Substantial impact of FDG PET imaging on the therapy decision in patients with early-stage Hodgkin's lymphoma

This prospective study assessed the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the staging and possible consequential changes of treatment regimen in patients with Hodgkin's lymphoma (HL). A total of 88 consecutive patients with histologically verified Hodgkin's lymphoma underwent a PET scan in addition to conventional staging procedures. Treatment was based on the conventional staging only, and the results of the FDG-PET did not affect the treatment strategy. The evaluation focused on the suggested change in clinical stage according to the Ann Arbor classification and on the suggested change in treatment strategy rather than on a lesion-by-lesion analysis. Using all the methods performed as the standard of reference, (18)F-FDG-PET staging was concordant with conventional staging in 70 out of 88 patients (80%). (18)F-fluorodeoxyglucose positron emission tomography suggested a change to a different clinical stage in 18 patients (20%). Management would have been changed in 16 patients (18%): intensification of treatment in nine patients (10%) and minimisation of treatment in seven patients (8%). In the 44 patients with early disease (stage IA-IIB), treatment would have been intensified in nine out of 44 patients (20%). (18)F-fluorodeoxyglucose positron emission tomography is a relevant noninvasive method that supplements conventional staging procedures and should therefore be used routinely to stage Hodgkin's lymphoma, particularly in patients with an early stage.     

Galactorrhea due to psychotropic drugs

Within the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie), severe adverse drug reactions (ADRs) are assessed. Currently 35 psychiatric hospitals and departments are participating in detecting severe ADRs. This paper focuses on prolactin-dependent ADRs such as gynecomastia and galactorrhea due to psychotropic medications. Related to the number of patients surveyed (122,562 from 1993 to 2000), these are rare events (0.03 % or 35 cases). Imputed drugs were mostly antipsychotics, but antidepressants were also imputed in single cases. In the group of antipsychotics, relative frequencies of galactorrhea were highest for amisulpride and risperidone and corresponded to the degree of D2 binding. Galactorrhea assessed as "severe" was accompanied by distressing symptoms such as pain, tension, enlargement of breasts, or soaked clothing. The AMSP data contribute to the knowledge on endocrine ADRs by the large number of patients examined and help clinicians select the appropriate drug if their patients have been prone to for these ADRs in the past.     

Role of myeloid cell factor-1 (Mcl-1) in chronic lymphocytic leukemia

The primary abnormality in chronic lymphocytic leukemia (CLL) is a defect in apoptosis, probably related to alterations in the expressions of Bcl-2 family members. In transgenic mice over expressing the anti-apoptotic Bcl-2 family member, myeloid cell factor-1 (Mcl-1), B cell lymphomas occur. Moreover, mice conditional for the loss of Mcl-1 display a profound reduction in B and T lymphocytes. This suggests that Mcl-1 is an essential survival factor in lymphocytes. In the present study, we have evaluated the role of Mcl-1 in CLL. Mcl-1 protein expression was measured by Western blot analysis in the CLL cells of 45 patients and correlated with clinical variables and survival. Mcl-1 levels were similar in 29 patients to normal B and T lymphocytes, were decreased in 8 patients and increased in 12 patients. An inverse correlation was found between Mcl-1 expression and Rai stage (P = 0.001). When assessed by flow cytometry, Mcl-1 expressions were normally distributed among CLL cells in individual patients and the mean levels correlated with those obtained by Western blotting. To evaluate the role of Mcl-1 in drug resistance, Mcl-1 levels were sequentially measured in the leukemic cells of 4 CLL patients during therapy with fludarabine (Flu). The Mcl-1 levels were found to increase in 2 patients while the peripheral blood lymphocyte counts dropped, suggesting that the residual drug-resistant cells had the highest Mcl-1 levels. Primary CLL cells were also treated with chlorambucil (CLB) or Flu in vitro and the Mcl-1 levels decreased correlating with the sensitivity of these cells to undergo apoptosis. Drug sensitivities of the CLL cells to CLB and Flu were also measured by MTT assay and the concentrations of drug required to decrease cell viability by 50% (IC50) varied from 1.9 to 9.27 microM for Flu (median, 9.4 microM) and 10 to 32.5 microM (median, 5.5 microM) for CLB. The sensitivities of the leukemic cells to CLB correlated inversely with Mcl-1 levels (P < 0.05). These results suggest that Mcl-1 may contribute to cell survival in CLL.     

Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma

The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.