Transitional cell carcinomatous meningitis after M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy

The M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen has been utilized at our two institutions to treat 17 patients with advanced stage transitional cell carcinoma of the bladder. We report 2 cases of carcinomatous meningitis resulting from metastatic transitional cell carcinoma which occurred in patients treated with M-VAC. Review of the literature suggests that our experience with central nervous system metastases is not unique, and that treatment of advanced stage transitional cell carcinoma of the bladder with M-VAC may enhance the incidence of meningeal metastases. Carcinomatous meningitis, although rare, is a rapidly fatal manifestation of metastatic transitional cell carcinoma if left untreated. However, prompt diagnosis and early aggressive therapy may result in palliation and stabilization of neurologic status. We review the pathophysiology, diagnosis, and treatment of transitional cell carcinomatous meningitis.     

Urea rebound and delivered Kt/V determination with a continuous urea sensor

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.      

Prevention of renovascular and cardiac pathophysiological changes in hypertension by angiotensin II type 1 receptor antisense gene therapy

Hypertension produces pathophysiological changes that are often responsible for the mortality associated with the disease. However, it is unclear whether normalizing blood pressure (BP) with conventional therapy is effective in reversing the pathophysiological damage. The duration and initiation of treatment, site of administration, and agent used all appear to influence the reversal of the pathophysiological alterations associated with hypertension. We have previously established that retrovirally mediated delivery of angiotensin II type 1 receptor antisense (AT₁R-AS) attenuates the development of high BP in the spontaneously hypertensive (SH) rat model of human essential hypertension. Our objective was to determine whether this attenuation of high BP is associated with prevention of other pathophysiological changes induced by the hypertensive state. Intracardiac delivery of AT₁R-AS in neonates prevented the development of hypertension in SH rats for at least 120 days. Contractile experiments demonstrated an impaired endothelium-dependent vascular relaxation (acetylcholine) and an enhanced contractile response to vasoactive agents (phenylephrine and KCl) in the SH rat renal vasculature. In addition, the voltage-dependent K⁺ current density, which is believed to contribute to smooth muscle resting membrane potential and basal tone, was decreased in renal resistance artery cells of the SH rat. AT₁R-AS treatment prevented each of these renal vascular alterations. Finally, AT₁R-AS delivery prevented the pathological alterations observed in the SH rat myocardium, including left ventricular hypertrophy, multifocal fibrosis, and perivascular fibrosis. These observations demonstrate that viral-mediated delivery of AT₁R-AS attenuates the development of hypertension on a long term basis, and this is associated with prevention of pathophysiological changes in SH rats.     

The psychiatric management of the globus syndrome

Controversy surrounding the term "globus hystericus" points up the historical dichotomy between organic disease and conversion disorder that has hampered the understanding of this syndrome. Regardless of its sometimes incapacitating nature, there is little information in the literature regarding the treatment of globus when an organic cause cannot be established. Regarding the syndrome as psychosomatic in nature, rather than merely hysterical, we suggest the need for an integrated treatment approach. A case study is utilized to illustrate a model for psychiatric management of the globus syndrome. In this model, pharmacologic and psychotherapeutic interventions are integrated into a comprehensive, biopsychosocial treatment plan. Each aspect of the model is reviewed and discussed.     

A quantitative analysis of the distribution of Purkinje cell axonal collaterals in different zones of the cat's cerebellum: an intracellular HRP study

Summary Purkinje cells in zones a and b of the vermis and zone c in the intermediate cortex of the anterior lobe were intracellularly injected with horseradish peroxidase and the distribution patterns of the varicosities present on their axonal collaterals were quantified and compared at the light microscopic level. The data derived from this study reveal that each individual axonal arbor had a unique pattern of distribution. However, certain principles of distribution could be applied to the collaterals regardless of the cortical location of the parent cell, including the following: 1) the total number of varicosities derived from the axonal collaterals of individual Purkinje cells is relatively uniform; 2) the collateral plexi have a greater extent in the sagittal plane as compared to the transverse plane; 3) the majority of varicosities remain within 200–300 m of the parent cell in both the sagittal and transverse planes; 4) there is a heterogenous distribution of varicosities within the area traversed by the axonal branches; and 5) the majority of varicosities are located within the Purkinje cell layer. Although there were similarities in the pattern of distribution for collaterals, there were also variations which distinguished the plexi in the three zones. The collaterals of zone a cells tended to be the most confined in both the sagittal and transverse planes. In contrast, several cells in zone b and c had branches that extended for relatively long distances in the sagittal plane. In zone b the collaterals have an asymmetric distribution around the cell of origin in the transverse plane. In zones a and c there is a tendency for a more symmetric pattern of distribution in this plane. The similarities in the number and laminar distribution of varicosities, as well as the predominantly sagittal orientation of the collaterals in all zones of the cerebellar cortex suggest that the collaterals subserve a common function throughout the cerebellar cortex. However, variations indicate that there may be subtle differences in the way recurrent collaterals process information in the cerebellar cortex that may be related to the functional heterogeneity or the location of the targets of the collaterals in the three zones analyzed.     

Directed establishment of rat brain cell lines with the phenotypic characteristics of type 1 astrocytes.

Interest in obtaining cell lines for use in studies on the development and biochemistry of the central nervous system has motivated efforts to establish cells from primary brain cultures by the use of oncogene-transfer techniques. In previous reports, cell lines derived from astrocytes in this way have had immature or abnormal phenotypes. We have explored the possibility of specifically "targeting" expression of exogenous oncogenes to differentiated astrocytes by using the promoter of the gene encoding glial fibrillary acidic protein, which is expressed almost exclusively in such cells. We report here that cell lines displaying the phenotypic characteristics of type 1 astrocytes can be established reproducibly in this manner. Given the heterogeneity of primary cultures, the availability of clonal cell lines displaying characteristics of type 1 astrocytes should greatly facilitate our understanding of the biology of these cells.     

Expression of cadherins and CD44 isoforms in ovarian endometrial cysts

We evaluated the immunohistochemical expression of cadherins and CD44 variants in 20 endometriomas, 20 cystadenomas, 20 borderline ovarian tumours as well as 20 ovarian carcinomas, and the serological and cystic fluid concentrations of soluble E-cadherin and soluble CD44 standard (sCD44sdt) in 20 endometriomas, 20 cystadenomas, six borderline and 11 carcinomas of the ovary. In endometriomas, immunostaining of E- and N-cadherin was negative (20 and 30% respectively). CD44 H, v3 and v6 immunostaining were detected in 63, 10 and 40% respectively. A difference in immunostaining for E-cadherin was found between endometriomas and cystadenomas (P < 0.001) and for N- cadherin between endometriomas and carcinomas (P < 0.001). A difference in CD44H immunostaining was observed between endometriomas and cystadenomas (P < 0.035) but not with borderline ovarian tumours and carcinomas. No difference in serum concentrations of soluble E- cadherins and CD44 standard was found between the four groups of tumours. Cystic fluid concentrations of E-cadherin were lower in endometriomas than in borderline tumours and ovarian carcinomas (P < 0.001). High concentrations of soluble CD44 standard cystic fluid were found in endometriomas than in other ovarian cysts. Endometriomas and borderline tumours share alterations of cadherins and CD44 isoforms which may help in the understanding of the aggressive and invasive potentials of endometriotic cells.