Our experience with 23 consecutive patients on gemcitabine/carboplatin chemotherapy for treatment of metastasized transitional cell carcinoma of the urothelium

AIM: To evaluate the activity and toxicity of gemcitabine plus carboplatin in patients with metastatic transitional cell carcinoma (TCC) of the urothelium. METHODS: Twenty-three consecutive patients (from February 1999 to January 2002) with metastatic TCC and no prior chemotherapy were referred to our institution. Each patient was treated with gemcitabine (1000 mg/m2) on Days 1 and 8 and carboplatin (area under curve, 4.5) on Day 1. Cycles were repeated every 21 days until tumor progression or severe toxicity was seen, or for a maximum of six cycles. Median age of the patients was 68 years (range 47-82). The median Eastern Cooperative Oncology Group (ECOG) performance score was one and the median creatinine clearance rate was 56 mL/min (range 31-94). RESULTS: The overall response rate was 60.8%, with five of the 23 patients achieving a complete response, and nine showing a partial response. Median time to tumor progression (TTP) was 7.8 months, with a median survival of 15.4 months and a 1-year survival probability of 56%. Most of the complications from toxicity were hematological. CONCLUSIONS: Gemcitabine plus carboplatin is active in the treatment of metastatic urothelial cancer in those patients new to chemotherapy and has an acceptable safety profile. The potential clinical benefit of this novel combination in the treatment of transitional cell carcinoma warrants further testing in Phase III studies.     

Stereological estimation of the volume weighted mean volumes of alveoli and acinar pathways in the rat lung to characterise alterations after ischaemia/reperfusion

The aim of this study was to characterise pulmonary reimplantation injury in isolated, perfused rat lungs following 2 h of cold ischaemia, and 50 min. of in vitro reperfusion. The effects of 2 differently composed lung preservation solutions (low potassium Euro-Collins and Celsior; each n=5) were examined in comparison with untreated, nonischaemic control lungs (n=3). After fixation by vascular perfusion and tissue collection by systematic random sampling, the volume weighted mean volume (_v) of alveoli and acinar pathways was estimated by light microscopic stereology using the method of point sampled intercepts in plastic embedded, Azan-stained material. Significantly higher _v of alveoli and acinar paths was found in the Celsior group than in Euro-Collins preserved lungs. However, in the controls the size of acinar pathways was similar to Celsior preserved lungs whereas alveolar size was comparable to preservation with Euro-Collins. The between-animal coefficient of variation of alveoli was very low in controls and Celsior preserved but higher in the Euro-Collins group. Size distribution of alveoli and acinar paths in 15 size classes was largely homogeneous in all groups tested. In the Euro-Collins group the fractions of both class 1-alveoli and class 1-acinar paths significantly exceeded those of the other groups. Widely expanded alveoli (size classes 13–15) only occurred after preservation with Celsior whereas wider acinar paths (size class 15) were found in the Celsior group and in the controls. It is concluded that lung preservation with low-potassium Euro-Collins and Celsior solutions may act differently on distinct spaces in the distal gas-exchange regions of lungs. This may be due to selective effects on pulmonary surfactant activity and on elastic tissue elements in the alveolar ducts, respectively. Additionally, the method of point sampled intercepts is considered to be an efficient tool to evaluate the effects of different preservation solutions on lung parenchyma.     

Electrophysiology of the Right Anterior Approach to the Atrioventricular Node:

Electrophysiology of Anterior AVN Input. Introduction: Previous reports have described electrophysiologic properties and rate-dependent responses in the transitional cell zone of the posterior AV nodal input (slow pathway). The purpose of this study was to investigate the electrophysiology of the anterior transitional cell zone (fast pathway) in vivo and in a Langendorff preparation perfused with a nonblood solution containing butanedionemonoxime to inhibit contraction. Methods and Results: In five anesthetized dogs, the His-bundle electrogram recorded from the aortic root included atrial activity in close proximity to the anterior limbus of the fossa ovalis. During decremental atrial pacing, the atrial potential exhibited amplitude alternans at a pacing cycle length (CL) of 135 ± 14 msec. In ten isolated pertused canine hearts, a bipctlar electrode catheter was positioned with its tip against the right anterior interatrial septum just superior to the tendon of Todaro. The AV Wenckebach CL (WCL) averaged 262 ± 21 msec. During further decreases in pacing CL, the bipolar atrial potential developed a 2:1 amplitude alternans (9/10 dogs) at CL = 168 ± 15 msec and then split into two components with subsequent 2:1 block between these components (10/10 dogs) at CL = 152 ± 19 msec. Radiofrequency ablation at this site in six dogs prolonged the stimulus to HB interval from 113 ± 19 to 151 ± 30 msec (P < 0.01) without changing the WCL, consistent with ablation of the fast AV nodal pathway. In six other isolated perfused canine hearts, an octapolar catheter (2-mm spacing) was positioned along the anterior limbus of the fossa ovalLs with the tip electrode located over the anterior portion (apex) of the triangle of Koch. The aforementioned 2:1 amplitude alternans occurred at a longer CL in the distal electrodes located at the tendon of Todaro than in the proximal electrodes at farther distances from the tendon of Todaro (185 ± 25 vs 171 ± 20 msec, P < 0.05), as did the 2:1 block between the two components (161 ± 18 vs 150 ± 18 msec, P < 0.05). Microelectrode recordings obtained adjacent to the catheter demonstrated 2:1 alternans and block patterns in the action potentials of transitional cells but not in atrial cells, which exhibited 1:1 conduction at all CL. Conclusions: The transitional cell zone in the anterior interatrial septum exhibits a specific rate-dependent, spatial gradient of conduction block, which can be recorded in bipolar electro-grams as well as microelectrode recordings. Electrophysiologic changes induced by radiofrequency ablation of this anterior atrial/transitional cell zone (corroborated by histology) provide strong presumptive evidence that this area constitutes all or a major part of the fast AV nodal pathway.     

Effects of Air Abrasion and Acid Etching on the Microleakage of Preventive Class I Resin Restorations: An In Vitro Study

Abstract: Purpose: To evaluate the effects of air abrasion, acid etching, and the combination of both procedures on the microleakage of preventive Class I resin restorations.
Materials and Methods: Eighty-four extracted human molar teeth were randomly assigned to seven groups with 12 teeth each. Occlusal fissures were opened with a diamond bur and etched with phosphoric acid (groups I and VI); prepared with a diamond bur without etching (group VII); air abraded with the KCP 1000, using SO-pm aluminum oxide particles without etching (group 11), and with phosphoric acid etching (group 111); or air abraded with 27-pm aluminum oxide particles without etching (group IV), and with phosphoric acid etching (group V). Preparations were filled with a low-viscosity resin composite (Liquicoat, groups I to V) or with a low-viscosity poly acid-modified resin composite (PrimaFlow, groups VI and VII). Six teeth in each group were thermo-cycled (5°-55°C, 2500 cycles). Dye penetration (methylene blue) was evaluated in ordinal scale.
Results: The number of non-thermocycled and thermocycled specimens revealing no microleakage was as follows: group I, 6 and 1; group II, 2 and 2; group III, 4 and 3; group IVY 0 and 0; group V, 1 and 0; group VI, 3 and 2; and group VII, 0 and 0, respectively. No significant differences existed between the thermocycled specimens and non-thermocycled specimens, except within group I.     

Antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on bladder cancer cell line T-24

AIMS: Bladder cancer, the fourth highest incident cancer in men and tenth in women, is associated with a high rate of recurrence, even when treated in situ, and prognosis is poor once the cancer metastasizes to distant sites. Based on anticancer properties, we investigated the effect of a mixture of lysine, proline, arginine, ascorbic acid, and green tea extract on human bladder cancer cells T-24 by measuring: proliferation, matrix metalloproteinase (MMP) expression, and cancer cell invasive potential. METHODS: Human bladder cancer cells T-24 (ATCC) were grown in McCoy medium supplemented with 10% fetal bovine serum, penicillin (100 U/mL) and streptomycin (100 mg/mL) in 24-well tissue culture plates. At near confluence, the cells were treated with the nutrient mixture dissolved in media and tested at 0, 10, 50, 100, 500, and 1000 microg/mL in triplicate at each dose. Cells were also treated with PMA 200 ng/mL to study enhanced MMP-9 activity. Cell proliferation was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. RESULTS: Nutrient mixture inhibited the T-24 cell secretion of MMP-2 and -9, with virtual total inhibition of MMP-2 at 500 microg/mL and MMP-9 at 100 microg/mL. The nutrient mixture significantly reduced the invasion of human bladder cancer cells T-24 through Matrigel in a dose-dependent fashion, with 95% inhibition at 500 microg/mL and 100% at 1000 microg/mL nutrient mixture (P < 0.001). CONCLUSION: Our results suggest that our nutrient mixture is an excellent candidate for therapeutic use in the treatment of bladder cancer, by inhibiting critical steps in cancer development and spread, such as MMP secretion and invasion.     

Several Unsuccessful Internal and External Defibrillations During Active Can ICD Implantation in a Patient with Pneumothorax

During implantable cardioverter defibrillator (ICD) implantation of an active can ICD several defihrillations with 20 J and 34 J as well as 360 J externally were ineffective. The implant criteria were finally met with a second defibrillation lead and reversed polarity. A left-sided pneumothorax due to subclavian vein puncture was detected soon after ICD implantation. It is assumed that especially in the active can alignment the developing pneumothorax made defibrillation current flow more difficult. In case of several unsuccessful defibrillations during active can ICD implantation in which the subclavian vein was punctured, the possibility of a pneumothorax should be considered.     

Intramyocardial Electrogram Variability in the Monitoring of Graft Rejection After Heart Transplantation

The ventricular evoked response is a well-standardized electrophysiological signal that can be used for noninvasive, long-term cardiac transplant monitoring. Rejection-sensitive and infection-specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection-sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection-sensitive parameter. A change in position from supine to upright did not influence the rejection-sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.     

DDD Pacemaker Implantation After Fontan-Type Operations

HEINEMANN, M.K., et al. : DDD Pacemaker Implantation After Fontan-Type Operations. Bradyarrhythmias developing after Fontan-type operations impair the function of the univentricular heart causing fatigue, headaches, ascites, and protein-losing enteropathy (PLE). Transvenous inaccessibility, requiring epicardial implantation, accounts for the reluctance to implant a pacemaker (PM). Between 1997 and 2000, 24 patients (mean age 9.5 years, range 6 months to 19 years) with Fontan-type operations received DDD pacing systems with atrial steroid-eluting stitch-on electrodes (mean capture threshold 1.9 V/0.5 ms, range 0.4–3.5 V) and ventricular screw-in electrodes (mean capture threshold 1.7 V/0.5 ms, range 0.1–3 V). The systems were implanted at the time of conversion from atrio- to cavopulmonary connections in 5 patients, at the time of a total cavopulmonary Fontan operation in 6, and 1–50 months thereafter (mean = 18) in 13 patients. A right ventricular anatomy was present in 13 (54%) of 24 of PM recipients, versus 35% of the overall population. After a mean follow-up of 3.5 years, the PM were functioning in DDD mode in 23 of the 24 patients. Length of hospital stay in the ten patients who underwent repeat sternotomy was 5 days, without procedure related complications. In three children a repeat sternotomy was avoided by implanting the atrial electrodes during the Fontan operation. All patients improved clinically, including resolution of PLE in four patients. Bradyarrhythmias may lead to significant morbidity after Fontan-type operations. Electrophysiological evaluation is advised at follow-up. The indication for implantation of a DDD pacemaker system should be liberal. Placing atrial electrodes during the Fontan operation, especially in the presence of a right ventricular anatomy, avoids repeat sternotomy. (PACE 2003; 26[Pt. II]:492–495)