Immunotherapy for superficial bladder cancer. A developmental and clinical overview.

Superficial bladder cancer is one of the few solid human malignancies in which immunotherapy has been proved to be effective. Bacillus Calmette-Guérin was the vaccine which opened the door for this innovative approach. In an era of remarkable achievements in biotechnology, it is truly amazing that this throwback to the Stone Age of tumor immunology has not yet been replaced by a more (or equally) effective substitute. Potential candidates are already on the horizon and deserve a comprehensive evaluation. They must show not only that they are devoid of significant adverse effects but that they possess, beyond a doubt, superior antineoplastic activity. Even more remarkable is that one of the oldest vaccines still in use could emerge in a new role as an effective antineoplastic agent. Bacillus Calmette-Guérin has demonstrated an uncanny capacity for effectiveness as therapy for human diseases. Its protective effect against tuberculosis is well recognized, and its contribution to cancer therapy is widely known. A new and increasing repertoire has recently been presented: two separate groups of researchers have employed the vaccine successfully as a vehicle to express antigen-encoded genes from other pathogens. The exciting aspect of these recent studies resides in the demonstration that the altered vaccine is able to induce humoral and cell-mediated immune responses to the recombinant antigens, including the human immunodeficiency virus (HIV). Thus, BCG once more attracts enormous interest from the scientific community for its versatility and potential as a therapeutic agent.     

Studies on the pharmacokinetics and metabolism of 4-chlorodiphenyl ether in rats

The metabolic disposition of 14C-labeled 4-chlorodiphenyl ether ([14C]4-CDE) was examined in rats following iv administration of a single dose (850 nmol/kg). [14C]4-CDE decayed rapidly from the blood since no unchanged [14C]4-CDE was detected in the blood beyond 2 hr after [14C]4-CDE administration. The dispositional kinetics of [14C]4-CDE in rats were best described by a two-compartment open pharmacokinetic model. Total radioactivity was excreted slowly from rats; about 41% and 33% of the administered dose were excreted into the urine and feces, respectively, within 1 week after chemical administration. About 5% of the total radioactivity administered to rats was excreted into the bile in 1 hr. The bulk of the radioactivity in the excreta was due to the presence of [14C]4-CDE metabolites. 14C-labeled 4'-hydroxy-4-CDE was the major metabolite and accounted for at least 90% of the radioactivity in the urine. The metabolic conversion of [14C]4-CDE to 14C-labeled 4'-hydroxy-4-CDE was corroborated by in vitro studies with liver microsomes of rats. In addition, [14C]4-CDE was converted by liver microsomes to reactive metabolites which bound irreversibly to microsomal protein. An arene oxide is suggested as the intermediate metabolite in the biotransformation of [14C]4-CDE by rats.     

Craniofacial screening profile: quick screening for congenital malformations.

The correct identification of syndromes and other congenital malformations at an early age is critical for the child, family and care providers. Most specialists who conduct large screenings of young children are not adequately trained to recognize signs and symptoms that should lead to appropriate referral to the clinical geneticist and/or diagnostic team. A systematic approach for recognizing important signs is presented here; a Craniofacial Screening Profile. Following a brief training program, the Profile was validated by 39 speech-language pathologists in screening 3,539 kindergarten and first grade children. The results were excellent (specificity was 99.6%), demonstrating that with limited training, specialists can effectively screen for important signs and symptoms of a major group of syndromes and other congenital malformations.     

Use of acute peritoneal dialysis catheters for intraperitoneal chemotherapy instead of the semipermanent/permanent Tenkhoff catheters

Intraperitoneal chemotherapy was administered to 13 patients with peritoneal carcinomatosis, using acute peritoneal dialysis catheters immediately before the administration of the chemotherapy. A total of 59 cycles were administered, with insertion of the corresponding catheter. There were no inflow or outflow problems and no insertion-related complications. With the removal of the catheter after its use, there is no risk of abdominal infections.     

Effect of diazepam on successive negative contrast in one-way avoidance learning.

The effect of administration of diazepam on successive negative contrast in one-way avoidance learning was examined in rats. Contrast was induced by shifting rats from a large reward, 30 s spent in the safe compartment, to a small reward, 1 s spent in the safe compartment. IP administration of 2 mg/kg diazepam eliminated this negative contrast. Moreover, this effect is dose dependent, with doses of 2 and 2.5 mg/kg, but not 0.5 mg/kg, effective in reliably reducing contrast. These results suggest the existence of similar or common underlying mechanisms in both aversive and appetitive contrast effects; they are discussed in light of the current theories of frustrative nonreward and as a mean of studying the behavioral and biological mechanisms of anxiety.     

Nicardipine improves motor tics

Calcium channel blockers can act on dopaminergic systems, and some reports suggest that they could be useful for the treatment of several movement disorders. In order to assess the efficacy of nicardipine in tics disorders we performed a prospective open non-controlled study which included 10 previously untreated patients. Our results suggest that nicardipine could be a useful and safe treatment for tics.     

L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

Transpubic approach for lower urinary tract surgery: a 15-year experience

Surgery on lower urinary tract organs sometimes is hindered by the symphysis pubis, which by its position and bulk could severely restrict maneuverability. Since 1972 we used a transpubic approach to improve surgical exposure in 287 patients operated on for prostate, bladder or urethral cancer, post-traumatic strictures and other conditions. The type of pubectomy performed (total, partial superior or partial inferior) depended upon whether a suprapelvic or infrapelvic diaphragm organ was the primary target of the approach. Total pubectomy was used in 137 patients, partial superior bone resection in 140 and partial inferior resection in 10 patients. Technical details for each type of pubectomy are illustrated. The transpubic approach was particularly useful for repair of posterior urethral strictures or removal of bulky tumors. Among the 3 types of approaches used, total pubectomy was associated with a high complication rate including bleeding, pelvic instability, urinary incontinence and stricture of the vesicourethral anastomosis. Therefore, we have abandoned the technique since 1978. Partial pubectomy provides exposure comparable to that of total pubectomy but with minimal complications, making it an alternative to the standard approach in difficult cases.