INFILTRATING CARCINOMA OF THE BLADDER: A NEW METHOD OF URETERO-INTESTINAL ANASTOMOSIS EMPLOYED IN 29 CASES; INDICATIONS FOR TOTAL CYSTECTOMY*

A method of uretero-intestinal implantation of the intact ureters in two stages, combined with total cystectomy at the second stage, has been described. When properly done it usually is followed by no permanent obstruction to the upper urinary tract. In my series of 29 cases in which both stages of the ureteral transplantation have been completed, there were only 3 patients who died as the specific result of the uretero-intestinal anastomosis. The causes in 2 of these cases have been determined and subsequently eliminated by improvement in the surgical technique. In 4 other elderly patients with advanced carcinoma there were 2 deaths from coronary occlusion, 1 from pulmonary embolus, and 1 from volvulus. Radical surgery no.w is limited to patients who are good surgical risks, and in whom there is a reasonable chance of cure. To be suitable for radical cure by total cystectomy, metastases must be absent, and the tumor must be completely confined to the bladder wall and freely movable. This latter condition is best determined pre-operatively by recto-abdominal palpation under anaesthesia. The opposition to total cystectomy for cancer of the bladder which is otherwise incurable has been based on two principal considerations: (1) The results of the rerouting of the urinary stream have been too uncertain, and (2) a surgical procedure which contemplates two laparotomies has seemed too formidable. These objections should be largely eliminated by the results obtained in this series of 29 cases. Certain authors have also objected to cystectomy because the incidence of radical cures of the cancer has not been impressive. I believe the principal reason for this is that ureteral transplantation previously has been so hazardous that this operation and cystectomy usually have been postponed until the cancer has become advanced and the patient's condition desperate. When this stage is reached the opportunity for obtaining a radical cure has been missed. The restriction of total cystectomy to cases without metastases in which the primary tumor is completely confined to the bladder wall and freely movable should increase the incidence of radical cures.     

In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography.

Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands.     

Changes in dielectric properties at 460 kHz of kidney and fat during heating: importance for radio-frequency thermal therapy

We have developed a system to measure the changes due to heating to high temperatures in the dielectric properties of tissues in the radio-frequency range. A two-electrode arrangement was connected to a low-frequency impedance analyser and used to measure the dielectric properties of ex vivo porcine kidney and fat at 460 kHz. This frequency was selected as it is the most commonly used for radio-frequency thermal therapy of renal tumours. Tissue samples were heated to target temperatures between 48 and 78 degrees C in a hot water bath and changes in dielectric properties were measured during 30 min of heating and 15 min of cooling. Results suggest a time-temperature dependence of dielectric properties, with two separate components: one a reversible, temperature-dependent effect and the other a permanent effect due to structural events (e.g. protein coagulation, fat melting) that occur in tissues during heating. We calculated temperature coefficients of 1.3 +/- 0.1% degrees C(-1) for kidney permittivity and 1.6% degrees C(-1) for kidney conductivity, 0.9 +/- 0.1% degrees C(-1) for fat permittivity and 1.7 +/- 0.1% degrees C(-1) for fat conductivity. An Arrhenius model was employed to determine the first-order kinetic rates for the irreversible changes in dielectric properties. The following Arrhenius parameters were determined: an activation energy of 57 +/- 5 kcal mol(-1) and a frequency factor of (6 +/- 1) x 10(34) s(-1) for conductivity of kidney, an activation energy of 48 +/- 2 kcal mol(-1) and a frequency factor of 6 x 10(28) s(-1) for permittivity of kidney. A similar analysis led to an activation energy of 31 +/- 4 kcal mol(-1) and a frequency factor of (4.43 +/- 1) x 10(16) s(-1) for conductivity of fat, and an activation energy of 40 +/- 4 kcal mol(-1) and a frequency factor of 4 x 10(22) s(-1) for permittivity of fat. Structural events occurring during heating at different target temperatures as determined by histological analyses were correlated with the changes in the measured dielectric properties.     

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis

CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES: To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN: We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS: All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.     

Interferon-α activates cytotoxic function but inhibits interleukin-2-mediated proliferation and tumor necrosis factor-α secretion by immature human natural killer cells

Natural killer (NK) cells play an important role in host defense mechanisms against infection and neoplasia. Interferon- (IFN-) has been shown to activate NK cells and to augment their cytotoxic activity, albeit its role in the maturation pathway of NK cells has not been elucidated. The present study examined whether IFN- activates the immature NK subset (Free cells) to become cytotoxic and also ascertained whether IFN- uses the same pathway of activation as that mediated by interleukin-2 (IL-2). Incubation of sorted Free cells overnight with IFN- resulted in augmentation of their cytotoxic function against NK sensitive target cells. The enhanced cytotoxic activity was not accompanied by a new recruitment of NK-target binder cells but by an increase in the frequency of killer cells in the conjugate fraction. Activation of the Free subset by IFN- resulted in upregulation of CD69, CD11b, and CD2 surface expression and stimulated secretion of IFN-. Unlike IL-2, IFN- did not stimulate the Free cells to proliferate or secrete TNF- and activation of cytotoxicity and modulation of surface antigens by IFN- were independent of TNF-. The failure of IFN- to stimulate secretion and proliferation by Free cells appeared to be mediated by negative signals. This was corroborated in experiments demonstrating that when Free cells were cultured with both IFN- and IL-2, a significant inhibition was observed for both the IL-2 dependent secretion of TNF- and proliferation. These results demonstrate that IFN- serves as both an activator and a regulator of NK function. Further, activation of the immature Free NK cells by IL-2 and IFN- proceeds by TNF--dependent and independent pathways, respectively. The findings also support our contention that the mechanism of activation of the cytotoxic machinery of NK cells is not linked to the mechanism of activation of cytokine secretion and/or proliferation.Abbreviations used IFN interferon - IL interleukin - PBL peripheral blood leukocytes - PE phycoerythrin - PE-GAM PE-conjugated Fab2 goat anti-mouse IgG - NK natural killer - NRS normal rabbit serum - TNF tumor necrosis factor - FCS fetal calf serum - FITC fluorescein isothiocyanate - PBS phosphate-buffered saline - MACS magnetic cell sorting - ELISA enzyme-linked immunosorbent assay - BSA bovine serum albumin - PKC protein kinase C - mAb monoclonal antibody - PBMC peripheral blood mononuclear cells - BCLL B-chronic lymphocytic leukemia - E effector - T target     

Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum

It is largely unknown why a variety of bacteria present in the oral cavity are capable of establishing themselves in the periodontal pockets of nonimmunocompromised individuals in the presence of competent immune effector cells. In this paper we present evidence for the immunosuppressive role of Fusobacterium nucleatum, a gram-negative oral bacterium which plays an important role in the generation of periodontal disease. Our studies indicate that the immunosuppressive role of F. nucleatum is largely due to the ability of this organism to induce apoptotic cell death in peripheral blood mononuclear cells (PBMCs) and in polymorphonuclear cells (PMNs). F. nucleatum treatment induced apoptosis of PBMCs and PMNs as assessed by an increase in subdiploid DNA content determined by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling assays. The ability of F. nucleatum to induce apoptosis was abolished by either heat treatment or proteinase digestion but was retained after formaldehyde treatment, suggesting that a heat-labile surface protein component is responsible for bacterium-mediated cell apoptosis. The data also indicated that F. nucleatum-induced cell apoptosis requires activation of caspases and is protected by NF-kappaB. Possible mechanisms of F. nucleatum's role in the pathogenesis of periodontal disease are discussed.     

Discriminative stimulus effects of combinations of drug and visual stimuli in pigeons

Six pigeons were studied to determine whether the brightness of a houselight interacted with the stimuli produced by methadone, and whether the nature of the interaction depended on the order of training of the two discriminations. Three pigeons were trained to peck the right key after methadone (2.0mg/kg) and the left key after saline, when the houselight was dim. The effects of a range of methadone doses (0.5, 1.0, 2.0mg/kg and saline) were tested. Three other pigeons were trained, in the absence of drug, to peck the right key when the houselight was dim and the left key when the houselight was bright. The effects of a range of houselight intensities were tested. Then, for both groups, right-key pecks were reinforced in the presence of methadone and the dim houselight, and left-key pecks were reinforced in the presence of saline and the bright houselight. Methadone doses were tested in the presence of both houselight brightnesses used in training. All pigeons pecked the methadone-appropriate key after high doses of methadone, regardless of houselight intensity. All pigeons trained to discriminate houselight brightness first, and one of the pigeons trained to discriminate methadone first, pecked according to the houselight condition when saline and lower doses were tested. In the other pigeon trained to discriminate methadone first, pecking was more related to drug dose. These data show that a drug stimulus can compete with external stimuli for behavioral control, that a drug stimulus can assume control over behavior originally controlled by external stimuli, and that discriminations based on external stimuli may be retained when saline or low doses of drug are administered.