Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia

Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long- term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer.     

Magnetic resonance imaging in young adults with cystic fibrosis

It is difficult to distinguish between atelectasis, mucoid impaction, and peribronchial inflammation on chest roentgenograms (CXR) in patients with cystic fibrosis (CF). Differentiation between hilar adenopathy and prominent pulmonary vessels is also sometimes difficult. We studied 16 young adults with CF using both magnetic resonance imaging (MRI) and CXR to evaluate the usefulness of MRI in this clinical context. The same patients were studied with abdominal ultrasound and MRI for evaluation of the pancreas, gallbladder, liver, and spleen. The MRI was superior to CXR in detecting hilar and mediastinal adenopathy and in differentiating nodes from prominent vessels. It was useful in the evaluation of bronchiectasis. The CXR was superior for assessing infiltrates, hyperinflation, sternal bowing, volume loss, and hilar retraction. The MRI was only slightly better than sonography in depicting fatty infiltration of the pancreas. The modalities were equally effective in detecting hepatosplenomegaly and signs of portal hypertension. Gallbladder evaluation was far superior with sonography.     

Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen

Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance.     

Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity

We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies.     

Open surgical partial nephrectomy for upper tract urothelial carcinoma

We aimed to determine the ability of partial nephrectomy to prevent end‐stage renal disease and tumor recurrence or progression in patients with upper tract urothelial carcinoma. Retrospectively, eight patients undergoing partial nephrectomy for upper tract urothelial carcinoma were identified and their medical records reviewed. All patients had imperative indications for nephron sparing, and diagnosis of upper tract urothelial carcinoma not adequately amenable to endoscopic management. Although three patients suffered acute tubular necrosis, only one required postoperative hemodialysis. During the follow‐up period 25% (2/8) developed end‐stage renal disease, including the one patient who had received postoperative hemodialysis. Recurrences occurred in five of seven patients with adequate oncological surveillance. Recurrences were successfully treated endoscopically in 80% (4/5) patients, and one patient had metastases. Of the eight patients, four have died. Death occurred 4 months, 1 year, 1.2 years and 3.5 years after partial nephrectomy. Of these patients, one succumbed to metastatic disease; the exact cause of death is unknown in the other three, but there was no documentation of metastatic cancer. The mean duration of follow up in the remaining four patients, all without evidence of metastatic urothelial cancer, is 71 months (range 22–108 months). In summary, partial nephrectomy for upper tract urothelial carcinoma in patients with imperative indications averts end‐stage renal disease in most patients, and appears to be associated with acceptable disease‐specific survival. Partial nephrectomy is a sparingly used option in patients with upper tract urothelial carcinoma refractory to endoscopic management who have imperative indications for nephron sparing.     

Subacute necrotizing encephalomyelopathy (Leigh disease): CT and MRI appearances

Subacute necrotizing encephalomyelopathy (SNE) is a genetic disorder of pyruvate metabolism. Until recently the diagnosis of SNE could only be made at autopsy. However, an antemortem diagnosis can now be suggested by the correlation of clinical and laboratory data with computed tomography (CT) and/or magnetic resonance imaging (MRI). Five children with clinical and laboratory data suggesting the diagnosis of Leigh disease were evaluated by CT and MR. MR was found to be more sensitive than CT in the detection of areas of necrosis in the brain of the five children we studied. The absence of focal lesions detected by either modality in one of our patients did not exclude the diagnosis of SNE since focal lesions were present at autopsy one month following CT and MR.     

Ureteroscopy for the treatment of urolithiasis in children

PURPOSE: Ureteroscopy for treating urolithiasis in prepubertal children has become more common with the advent of smaller instruments. We reviewed our experience with ureteroscopy for urolithiasis in this cohort of patients as well as the literature using this treatment modality in children. MATERIALS AND METHODS: Between 1994 and 2000 we performed 27 ureteroscopic stone extractions in 25 children. Ureteroscopy was done in a manner similar to that in adults. Ureteral dilation was performed when necessary to access the ureter. A stent was placed postoperatively if there was significant ureteral trauma. RESULTS: Of the 25 children 13 were male and 12 were female. Average age was 9.2 years (range 3 to 14). Stones were 2 to 12 mm. in greatest diameter (average 6). Of the 27 procedures the ureteral orifice was dilated before stone treatment in 15 (56%), while in 19 (70%) a stent was placed afterward. No intraoperative and 2 postoperative complications were identified. Overall 92% of the children were rendered stone-free after 1 procedure and 100% were stone-free after 2. CONCLUSIONS: Ureteroscopy for urolithiasis in prepubertal children is safe and effective. Routine ureteral dilation and ureteral stent placement are not always necessary in these patients.     

Ureteroscopic treatment of lower pole calculi: comparison of lithotripsy in situ and after displacement

PURPOSE: Ureteroscopic management is a viable option for lower pole calculi less than 2 cm. Recently a technique was described to displace the calculus into a more accessible calix using a nitinol basket or grasper before lithotripsy. We compared the efficacy and safety of this technique with in situ treatment of small and intermediate lower pole calculi. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 ureteroscopy cases performed at our institution from January 1997 through August 2001 for renal calculi located only in the lower pole. Preoperative patient characteristics, stone size, operative details, complications and outcomes were compared for calculi treated in situ and those displaced before treatment. RESULTS: Adequate followup was available on 78 patients. Patients in the displacement group were statistically older, more often had a preoperative indwelling ureteral stent and had a mean operative time that was 16 minutes longer (p = 0.04). Average stone diameter in the in situ and displacement groups was 8 and 10.3 mm., respectively (p = 0.04). In patients with radiographic followup greater than 1 month complete success was obtained for 77% of stones 1 cm. or less treated in situ versus 89% treated with displacement first (p = 0.43). For calculi greater than 1 cm. complete success was obtained for 2 of the 7 (29%) treated in situ versus all 7 (100%) treated with displacement (p = 0.005). CONCLUSIONS: When treating lower pole calculi 1 to 2 cm. via ureteroscopy, a higher success rate can be obtained with displacement into a more accessible calix before treatment.     

Currarino triad: Characteristic appearances on magnetic resonance imaging and plain radiography

The Currarino triad is a complex anomaly consisting of an anorectal malformation, a sacral bone defect and a presacral mass. It was first described in 1981 and since then, approximately 250 cases have been reported. Radiology has an important part to play in the diagnosis of this entity, as the imaging features are characteristic. We report a case of Currarino triad in an infant who presented with intractable constipation and discuss relevant MRI and plain radiography findings.