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J Sheinfeld

Publications and source records attributed to J Sheinfeld.

At least 19 recordsLinked to original sources

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.

Adult

Blood group antigens in normal and neoplastic urothelium.

The ABO and Lewis blood group antigens are cell surface carbohydrate determinants formed by the sequential addition of saccharides to precursor backbone structures of membrane lipids and proteins. Suppression of normally active glycosyltransferases results in the absence of antigens that are normally expressed. ABH antigen deletion in malignant and premalignant urothelium has been extensively evaluated; it appears to correlate with significantly higher rates of tumor recurrence and disease progression. However, we have recently shown that the ABH blood group system is differentially expressed in the normal urothelium of secretors in contrast to nonsecretor individuals. The normal urothelium of nonsecretors does not express A, B or H determinants; therefore, deletion of ABH antigens can only be ascertained in secretor individuals. Although nonsecretors only comprise 22-24% of the population, this observation mandates a reevaluation of earlier studies. Deletion of A, B or H antigens is noted in carcinoma in situ (CIS), and in invasive and metastatic transitional cell carcinoma (TCC) of secretor individuals. Increased synthesis or activation of normally quiescent glycosyltransferases in bladder tumors can result in the expression of aberrant tumor-associated blood group antigens. Immunohistochemical analysis has demonstrated that Lewis X (Le(x)) is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas, CIS and TCC expressed Le(x) in 84% of cases, regardless of grade, stage, blood type or secretor status of the individual. The presence of Le(x)-positive cells in bladder lavage specimens enhanced the detection of urothelial tumor cells, correctly identifying bladder tumors in 253/293 (86%) cases compared to a 63% sensitivity for cytology alone.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System

Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).

Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months). An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy. Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less. Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months). The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy. The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens.

Adolescent

Association of type 1 blood group antigens with urinary tract infections in children with genitourinary structural abnormalities.

Bacterial adherence to carbohydrate receptors on the surface of urothelial cells is important in the pathogenesis of urinary tract infections. Blood group-related antigens, genetically determined carbohydrate structures found on the urothelial cell surface, may influence the availability of these receptors thereby affecting bacterial adherence and the susceptibility to urinary tract infections. Recent evidence indicates that the immunoanatomical distribution of type 1 blood group-related antigens in urothelium is influenced by ABO, Lewis and secretor phenotypes, women with Le(a-b-) and Le(a+b-) blood phenotypes have more than a 3-fold greater risk of recurrent urinary tract infections compared to Le(a-b+) women and epithelial cells from nonsecretors have more bacterial receptors than cells from secretors. To determine the relation between the expression of type 1 blood group-related antigens and urinary tract infections we performed an immunohistochemical analysis using a well characterized panel of monoclonal antibodies on 72 surgical specimens obtained from children who underwent correction of a structural genitourinary anomaly at the University of Rochester Medical Center from December 1983 to May 1988. Of 72 children 48 had a history of at least 1 documented urinary tract infection. The differences in the distribution of children by type 1 blood group immunophenotype in the infection and noninfection groups were highly significant (p = 0.003, Fisher's exact test). There is an increased frequency of urinary tract infections in children with genitourinary structural anomalies whose urothelium reflects the nonsecretor phenotype, that is they have minimal or undetectable levels of ABO and Leb reactivity compared to those with intense ABO and/or Leb immunoreactivity. Of 17 children with minimal or no ABO or Leb immunoreactivity 16 (94.1%) belonged to the infection group. Furthermore, 23 of 24 patients (95.8%) without a history of urinary tract infection expressed intense ABO and/or Leb immunoreactivity. It appears that the type 1 blood group-related antigen profile of urothelium influences susceptibility to urinary tract infection and it may be important in identifying patients who would benefit from prophylactic antibiotic therapy or earlier surgical intervention.

ABO Blood-Group System

Enhanced bladder cancer detection with the Lewis X antigen as a marker of neoplastic transformation.

Recent evidence indicates that the Lewis X determinant is a tumor-associated antigen in the urothelium. Immunohistochemical analyses on frozen and deparaffinized, formalin-fixed tissue sections have demonstrated that the Lewis X antigen is not detected in normal adult urothelium except for occasional umbrella cells. However, papillomas and transitional cell carcinomas express this blood group-related antigen in more than 90% of the cases regardless of the grade or stage of the tumor, or the blood type or secretor status of the individual. To determine the presence of Lewis X antigen on exfoliated bladder epithelial cells we used an anti-Lewis X monoclonal antibody (P-12) and the avidin-biotin-peroxidase technique on 129 bladder barbotage specimens. Of 40 controls 34 were negative for Lewis X antigen, for a specificity of 85%. The 89 bladder tumor patients consisted of 14 with papilloma, 13 with flat carcinoma in situ, 49 with transitional cell carcinoma, and 13 with a positive cytology and negative biopsy results. Of these 89 patients 76 were considered positive for Lewis X antigen, for an over-all sensitivity 85.4%. The sensitivity for cytology alone was 61.2%. However, the combination of a positive cytology and/or positive Lewis X antigen result yielded a sensitivity of 93.2%. The data suggest that immunocytological detection of the Lewis X antigen on exfoliated bladder cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms.

Antibodies, Monoclonal

The T1 bladder tumor.

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Combined Modality Therapy

Recent diagnostic modalities for bladder cancer.

Recent advances in hybridoma technology, immunohistochemistry, cytopathology, cytogenetics, and molecular biology have not only furthered our understanding of the biology of bladder cancer but are also beginning to find clinical applications in the early diagnosis of the disease. It is likely that further study and refinement of these tools could reliably identify patients with superficial bladder tumors who are at increased risk for subsequent muscle infiltrative disease, or patients whose tumors are not amenable to current front-line chemotherapy.

Antigens, Neoplasm

Association of the Lewis blood-group phenotype with recurrent urinary tract infections in women.

Blood-group antigens are found on the surface of urothelial cells and may affect bacterial adherence and thereby the susceptibility to urinary tract infection. We determined the ABO, P, and Lewis blood-group phenotypes in 49 white women with histories of recurrent urinary tract infections and compared them with those found in 49 healthy control women without recurrent urinary tract infections. There was no significant difference between the two groups in the distribution of the ABO or P phenotypes. The distribution of Lewis blood-group phenotypes among control women was similar to that in the general population: secretor phenotype (Le(a-b+)), 74 percent; nonsecretor phenotype (Le(a+b-)), 18 percent; and recessive phenotype (Le(a-b-)), 8 percent. The following distribution was noted among the women with recurrent urinary tract infections: secretor phenotype, 45 percent; nonsecretor phenotype, 29 percent; and recessive phenotype, 26 percent (P = 0.002). When the women with nonsecretor and recessive phenotypes were combined and considered collectively, the odds ratio (an estimate of relative risk of recurrent urinary tract infection) for those without the secretor phenotype was 3.4 (95 percent confidence interval, 1.5 to 7.9). We conclude that there is an increased frequency of the Lewis blood-group nonsecretor (Le(a+b-] and recessive (Le(a-b-] phenotypes among women with recurrent urinary tract infections.

Adult

Blood group-related antigens in human kidney: modulation of Lewis determinants in renal cell carcinoma.

Seven mouse monoclonal antibodies and the lectin Ulex europaeus, detecting blood group related antigens of the ABH and Lewis systems, have been used to determine the immunophenotype of human renal cell carcinomas. Immunohistochemical analyses have demonstrated that these antigenic systems are differentially expressed by distinct normal cell types and domains of the human nephron. In the present study we analyzed the immunophenotype of 29 primary and 15 metastatic renal carcinomas by the immunoperoxidase method. Blood type was known in all of the cases and secretor status in nine cases. ABH specificities were not detected in tumor cells of the primary tumors studied, although two of the metastases showed heterogeneous expression of H and A antigens, respectively. Lewisx (Lex) determinant was detected in 76% of primary renal cell carcinomas; however, Lex was only expressed by occasional cells in 20% of the metastatic tumors analyzed. Lewisa (Lea) was detected with a heterogeneous pattern of expression in 31% of the primary and 26% of the metastatic renal tumors studied. Lewisy (Ley) antigen expression was found in 17% of the primary and 20% of the metastatic tumors analyzed. Detection of precursor type 1 structure was observed in 28% of primary and 20% of metastatic renal cell carcinomas. The present study suggests the histogenesis of renal cell carcinoma in the proximal nephron, based on the expression of Lex and Lea antigens. It also shows: (a) an apparent deletion, downregulation or structural modification of Lex determinant in most of the metastatic tumors; (b) undetectable levels of ABH specificities in tumor cells of primary renal cell carcinoma; and (c) enhanced expression and/or neosynthesis of precursor type 1 structure and Ley determinant in some renal cell carcinomas.

ABO Blood-Group System

Blood group-related antigens in human urothelium: enhanced expression of precursor, LeX, and LeY determinants in urothelial carcinoma.

Seven mouse monoclonal antibodies and the lectin from Ulex europaeus, detecting blood group specificities of the ABH and Lewis systems, have been used to define the expression and/or modulation of these antigenic structures in human normal urothelium and tumors of the urinary bladder. The reagents employed recognize the following blood group related antigens: A, B, H, Lewisa (Lea), Lewisb (Leb), Lewisx (Lex), Lewisy (Ley), and type 1 precursor chain. Immunohistochemical studies have demonstrated that these antigenic systems are differentially expressed in the urothelium of secretor and nonsecretor individuals. The normal urothelium of secretors is particularly rich in ABH blood group antigens as well as Leb and Ley specificities. Nonsecretors, however, either lack or show decreased and patchy expression of H, Leb, and Ley antigens. In general, areas affected by carcinoma in situ showed deletion of ABH, as did invasive carcinomas, as demonstrated by other investigators. This was not a universal observation, however, as variable expression of ABH antigens occurred in a few invasive tumors. Lex antigen was not expressed in normal urothelium except for occasional umbrella cells, but was demonstrated in the majority of invasive tumors, regardless of blood type and secretor status of the individuals studied. Ley determinant, which was poorly expressed in the normal urothelium of nonsecretor individuals, was found in all tumors analyzed. An accumulation of non-fucosylated precursor structure was also a feature of invasive carcinoma, particularly in secretor individuals. A panel of anti-blood group antibodies, encompassing A, B, Lex, Ley and type 1 precursor chain specificities for use in patients of known secretor status, may provide useful early markers of malignant change in the urothelium.

Adult

Metaplastic cystitis complicated with Von Brunn nests, cystitis cystica, and intestinal type of glandular metaplasia.

It is well documented that under certain stimuli the bladder epithelium can undergo metaplasia. The origin of glandular epithelium, which may be found in the bladder, is somewhat controversial. Endoscopic and histopathologic features of an eighty-one-year-old white man with proliferative metaplastic cystitis are presented. This case demonstrates that glandular differentiation was due to progressive cystitis rather than congenital intestinal rest.

Aged

Octoson imaging in pediatric urology.

Ultrasonic imaging of infants and children using an automated transducer water-path delay scanning system (Octoson) overcomes many of the technical difficulties of contact B mode ultrasound imaging and computed tomography. These disadvantages relate to small patient size, motion artifacts, hypothermia, and lack of patient cooperation. Sedation may be required for either conventional study. The automated water-path system is soothing to small children, maintains the body temperature of infants, and avoids direct transducer contact. Sedation is not necessary. Excellent resolution, shorter scan time than computed tomography, and greater flexibility of patient and transducer positioning allows much more complete imaging information. In addition, the panoramic view obtained using this modality serves to demonstrate the complete lesion and its relationship to surrounding structures.

Child

Voiding dysfunction in tertiary syphilis.

After years of decline to near disappearance, there recently has been an increasing incidence of syphilis in America. New cases of tertiary neurosyphilis are being reported which often have associated significant urologic sequelae. For the first time in the English literature, the uro-dynamic findings of a patient with tabes dorsalis are presented. Our findings indicate that treatment of urinary retention associated with tabes dorsalis is better managed by intermittent catheterization than by prostate surgery because of the impaired detrusor activity. A review of neurosyphilis and its urologic implications and urodynamic findings are presented. Prompt recognition of this entity should encourage a full urodynamic evaluation prior to a commitment to prostatic surgery.

Electromyography

The effect of graded unilateral testicular biopsy on the reproductive capacity of male rats.

Fifty adult rats were subjected to unilateral testicular biopsy removing either 0.01, 0.1, 0.2 or 0.3 cc of testicular parenchyma. In addition, 20 rats underwent either hemicastration or sham surgery. After a 30-day recovery period each male was housed with two cycling females for 20 days. At the end of this breeding trial the percentage of fertile males, percentage of pregnant females and resulting embryo scores (no. of embryos X size of embryos) were determined for each group of male rats. After an additional 30 days (60 days post-biopsy) a second breeding trial was performed so as to note any long-term changes in fertility. In addition to the fertility parameters, mean seminiferous tubule diameters and serum testosterone levels were noted. After the first breeding trial the percentage of fertile males and percentage of pregnant females were inversely proportional to the amount of biopsy material removed (p less than 0.05). However, the hemicastrate and sham-operated groups did not differ from the O cc control animals. The results of the second breeding trial showed a significant improvement in the percentage of females becoming pregnant (p less than 0.05) and a tendency for improvement in the percentage of fertile males when compared to data of the first breeding trial. In addition, we found the mean seminiferous tubular diameter of the biopsied testes to be inversely proportional to the size of the biopsy (p less than 0.01) with no apparent effect on the contralateral testes. We conclude that removing relatively large amounts of testicular parenchyma during unilateral testicular biopsy transiently affects male reproductive capacity, at least in the healthy animal model studied here.

Animals

Selective pre-transplant nephrectomy: indications and perioperative management.

From May 1977 to June 1983, 198 patients were accepted as candidates for renal transplantation at our university. We review our experience with 14 consecutive patients who underwent selective pre-transplant nephrectomy during this interval. Indications for this procedure included recurrent or chronic pyelonephritis, structural abnormalities of the urinary tract predisposing the patient to infection, malignant or renin-dependent hypertension, Goodpasture's disease, certain cases of rapidly progressive glomerulonephritis and selected patients with polycystic kidneys. All patients underwent dialysis 1 day preoperatively. Perioperative fluid losses were measured carefully with prompt and vigorous replacement therapy. Patients received an average of 5,890 cc fluid replacement before postoperative dialysis. All patients underwent dialysis within 29 hours postoperatively. There were no postoperative deaths and 8 complications. Selective pre-transplant nephrectomy has spared 93 per cent of potential renal transplant candidates from a major surgical procedure. No patient has required removal of the original kidneys during the post-transplant period. Our experience has shown that the reluctance to hydrate these patients is unwarranted and that prompt postoperative dialysis, if required, is safe. Since some end stage kidneys are physiologically active and the associated surgical risk is high, pre-transplant nephrectomy should be performed only in carefully selected patients. In contrast to previous reports, which advocated minimal fluid administration and delayed postoperative dialysis, our recent experience indicates that vigorous fluid replacement therapy, carefully monitored with serial vital signs, weights, serum electrolytes and central venous pressure readings, will avert many of the complications encountered previously.

Adolescent

Renal trauma: evaluation by computerized tomography.

The diagnosis and appropriate management of patients with renal trauma have remained controversial. From July 1981 to June 1984 we evaluated with computerized tomography 22 selected patients suspected of sustaining major renal trauma. Of these patients 17 were managed successfully with conservative therapy and 5 underwent surgical exploration. Only 2 patients required arteriography because of excellent renal delineation provided by computerized tomography scanning. Computerized tomography provides the most precise anatomical detail of renal injuries as well as valuable information regarding other retroperitoneal and intra-abdominal structures, often resulting in the identification of associated and unsuspected injuries. We advocate the use of computerized tomography as the primary diagnostic modality in patients suspected of sustaining major renal injury and/or other organ injuries. This change in diagnostic studies has facilitated greatly the diagnosis and treatment of kidney injuries.

Adolescent