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Between April 1986 and October 1992, a total of 229 patients with invasive bladder cancer underwent radical cystectomy and lower urinary tract reconstruction by means of the ileal neobladder. The perioperative mortality was 2.4%. Subsequently 10.5% of the patients suffered from early complications that led to relaparotomy and 3.8% of the patients had bowel occlusion. Significant late complications were urethro-ileal strictures (6.7%) and stenosis of the ureteral anastomosis (3.3%). Despite a very strict definition of continence, only 2 patients with a follow up of more than 2 years had an incontinence grade 3. Most (77%) of the patients in this collective were perfectly continent day and night, while 11.5% had only occasional spotting and wore pads to be on the safe side. In conclusion, the medium-term results are now available (average follow up 41 months) and show that the ileal neobladder is the treatment of choice for male patients after radical cystectomy for the treatment of invasive bladder cancer.

A full-length cDNA clone for a novel glutathione S-transferase was isolated from Arabidopsis thaliana and characterized. The cDNA encodes a polypeptide of 218 amino acids with a calculated molecular mass of 24,363 Da. The sequence was most related to the theta class within the glutathione-S-transferase superfamily of enzymes. The protein encoded by the cDNA was functionally expressed and enzymically active in Escherichia coli; glutathione-S-transferase activity with the standard enzyme substrate 1-chloro-2,4-dinitrobenzene was demonstrated (apparent Km, 10 mM; apparent Km for glutathione, 0.08 mM). The enzyme is substrate specific and did not use several electrophilic reduced-glutathione acceptor molecules for conjugation. However, it efficiently catalyzed the conversion of 13-hydroperoxy-9,11,15-octadecatrienoic acid (Km, 0.67 mM) as well as 13-hydroperoxy-9,11-octadecadienoic acid (Km, 0.79 mM) to the corresponding hydroxy derivatives with concomitant formation of oxidized glutathione. The enzyme did not use H2O2 as substrate. Thus, the cloned A. thaliana enzyme functions as glutathione peroxidase and, in the plant cell, may be involved in the removal of reactive organic hydroperoxides, such as the products of lipid peroxidation. The enzyme is structurally and enzymatically, however, unrelated to the selenium-containing glutathione peroxidases. Enzymic and immunoblotting data suggest that the A. thaliana enzyme is soluble and constitutively expressed in vegetative rosettes, but is under developmental control during the transition to bolting and flowering.

Between April 1986 and April 1992, 211 consecutive men underwent lower urinary tract reconstruction by means of the ileal neobladder. There have been 5 perioperative deaths for an operative mortality rate of 2.4%. The early complication rate for issues not directly related to the neobladder was 7.5% compared to a 6.5% directly neobladder-related early reoperation rate. Neobladder-related late complications requiring rehospitalization or reoperation have been acceptable, including ileus (2%), abscess (1%), colon-reservoir fistula (1.5%), hydronephrosis (1%), ureteral stenosis (3.6%) and transurethral incision of the urethroileal anastomosis (7%). Overall, only 29.3% of our patients had no complication, whereas 32% suffered significant problems requiring rehospitalization or reoperation. The remainder of the patients suffered minor but not negligible problems. Excellent continence was achieved early and increased with time: 85% of the patients were perfectly dry night and day by 3 years. At this date only 5.5% of the patients had nighttime incontinence, while 6% wear protection for occasional accidents. Intermittent catheterization is necessary in 3.5% of the patients because of the inability to void or maintain a post-void residual volume of less than 100 ml. Despite the fact that some price must be paid for excellent continence, natural voiding and undisturbed body image, the ileal neobladder continues to be our procedure of choice for male patients after cystectomy provided there is no evidence of prostatic or urethral involvement. Our results should stimulate earlier patient and physician acceptance of cystectomy.

Coexisting polymer phases are characterized by very small interfacial energies, even well below their critical solution temperature. This situation should readily lead to the exclusion of one of the phases from any interface that favors the other. Such complete wetting behavior from a binary mixture of statistical olefinic copolymers is reported. By means of a self-regulating geometry, it is found that the thickness of a wetting layer of one of the phases at the polymer-air interface, growing from the other coexisting phase, attains macroscopic dimensions, increasing logarithmically with time. These results indicate that binary polymer mixtures could be attractive models for the study of wetting phenomena.

Since April 1986, 227 patients received an ileal neobladder at our institution. Of these patients 206 underwent simultaneous radical cystectomy for bladder cancer, and 21 received a bladder augmentation. The mean postoperative follow-up ranges from 3-71 months. Perioperative mortality was 2.55 percent, 15 percent of the patients died later than 2 months postoperatively, 13.4 percent due to tumor progression, 1.5 percent because of pneumonia, severe metabolic acidosis, myocardial infarction and apoplexia. Day and night continence was preserved in 77 percent of the patients with a follow-up of more than 2 years; severe stress incontinence was found in 2 patients, and night time incontinence needing some external device in 4.6 percent. 11.5 percent with mild stress incontinence do not require further treatment. Our experience with this relatively simple procedure is excellent: the need for re-operation is low and the high reservoir capacity results in early continence in most cases. This concept offers a genuine alternative to any form of cutaneous urinary diversion with an incidence of complications not higher than after standard supravesical urinary diversion.

Dietary fiber deficiency may be alleviated with an increase in fiber-rich foods or fiber in the form of guar. The efficacy of a solid guar preparation and a liquid form on glucose and insulin levels during a glucose tolerance test in 12 healthy volunteers was examined. The first half of the study tested the efficacy of a new guar preparation (GU-052, Steigerwald, Darmstadt, Germany). Six volunteers ingested 75 glucose and 12 g guar mixed in 450 ml water. The other 6 received the same drink without guar. Blood was withdrawn for the determination of glucose and insulin before ingesting the glucose solution and after 15, 30, 45, 60, 90, 120, 180, 210 and 240 min. One week later the groups were crossed over. The second half of the study tested the efficacy of GU-052 against a solid preparation consisting of 5 g guar and 1.13 g additive (Glucotard, Boehringer, Mannheim, Germany). Volunteers receiving GU-052 with the glucose drink showed no increase in plasma glucose. Volunteers without GU-052 reached a maximal plasma glucose value of 6.66 +/- 1.30 mmol/l 30 min after glucose ingestion from an initial value of 5.28 +/- 0.40 mmol/l. A second smaller peak was observed 120 min after glucose ingestion. A 2.5-fold increase from 16.17 +/- 4.30 to 40.10 +/- 19.00 microIU/ml in insulin concentration occurred in the volunteers ingesting GU-052, whereas a 6-fold increase from 19.33 +/- 12.20 to 114 +/- 48.8 microIU/ml insulin occurred in the volunteers without GU-052. A second peak in insulin at 120 min which occurred in the volunteers without GU-052 was not apparent when the volunteers ingested GU-052. The comparison of GU-052 and Glucotard showed that GU-052 maintained the glucose level, whereas Glucotard allowed the plasma glucose to reach 6.67 +/- 0.98 microIU/l. The increase in insulin was not as great with GU-052 as with Glucotard. This study shows that guar suppresses glucose and insulin levels during a glucose tolerance test. The guar form influences the efficacy.

The method for differential fluorescence staining of cellular RNA and DNA by acridine orange (AO) was optimized for 3T3 and SV40-3T3 cells. Cellular contents of DNA and of ribosomal RNA (rRNA) were determined by dual-channel flow cytometry during cell-density-dependent proliferation and after stimulation of quiescent cells. With increasing density of 3T3 cells, cellular content of rRNA decreases by about 60%, whereas SV40-3T3 cells do not exhibit a significant dependence of rRNA content on cell density. 3T3 cells stimulated early after becoming quiescent resume reaccumulation of rRNA after a delay of only 4 h, whereas cells maintained at quiescence for several days exhibit a delay of about 12 h before a significant rise of rRNA is observed. The extent of rise of cellular rRNA content after different regimens of stimulation of quiescent 3T3 cells does not correlate well with the fraction of cells entering the cell cycle. These and other reported instances of discordance between rRNA content and stimulation into the cell cycle are resolved by showing that of the two signals governing entry into the cell cycle only the progression signal, but not the competence signal is associated with reaccumulation of cellular rRNA. The present results are consistent with the progression function being in essence the achievement of a threshold number of ribosomes per cell, which in conjunction with the competence signal is sufficient for initiation of the cell cycle.

The phenomenon of resistance of confluent 3T3 cells to serum stimulation of proliferation is investigated and shown to depend drastically on the kinetics of application of growth factors with the serum. The cellular content of ribosomal RNA is determined flow-cytometrically by measuring the red fluorescence of cells stained with acridine orange. Ribosomal RNA content of 3T3 cells, but not of SV40-3T3 cells, is shown to decrease after confluence. The kinetics of restoration of ribosomal RNA in stimulated 3T3 cells exhibits an increasing delay with increasing duration of quiescence. These and further results are consistent with "progression" to initiation of the cell cycle being closely associated with restoration of cellular content of ribosomes.

Subpopulations of different proliferative status are determined during cell-density dependent proliferation of 3T3 cells. From these data the probability of conversion of proliferative to quiescent cells is derived and found to correlate well with published data on binding of growth-inhibiting factors secreted from growth-inhibited cells.

Hydrophilic films of phospholipids were deposited onto plastic substrates (surface-treated for cell cultures) and shown to adhere sufficiently for measuring their interfacial properties by the method of contact angles. Both by absolute magnitude and by their dependence on temperature, the interfacial properties of these phospholipid films were indistinguishable from those determined for black lipid bilayer membranes with a different method by other authors. According to both their vesicular micromorphology and water permeability, the surface films can be interpreted to consist essentially of multibilayer vesicles with the hydrophilic groups facing outward. Treatment of these films with cell-culture medium containing calf serum results in changes of interfacial properties that are very similar to those effected on virus-transformed 3T3 cells (earlier work). These interfacial effects may be attributed essentially to serum proteins (such as albumin) adsorbing to phospholipid or cellular surfaces. The interfacial properties of nontransformed 3T3 cells are much less affected by serum treatment (earlier work), which correlates closely with their higher serum requirement for proliferation. Comparison of these results with those on the interfacial effects of serum on phospholipid films suggests that at least part of the proliferation-stimulating effect of serum is mediated by changes of interfacial properties of cell membranes upon adsorption of serum proteins such as albumin. Treatment of phospholipid films with concanavalin A, an inhibitor of cell proliferation, does not result in effects on their interfacial properties correlating with those on cellular membranes. This confirms previous suggestions that the latter depends on specific binding of concanavalin A to specific carbohydrates on the cell membrane.

The antihyperlipidaemic effect of a guar preparation which absorbs a particularly large amount of water has been examined in 13 patients with Type II hyperlipidaemia. A 30-day pre-treatment phase was followed by 60 days of treatment with 4 g guar dissolved in 200-ml liquid at each meal-time (total guar 12 g/day), and a 60-day post-treatment observation period. Routine other clinical blood tests were performed 30, 15 or 0 days before treatment, 15, 30 and 60 days after the start of treatment, and 30 and 60 days after its end. Total cholesterol fell by 0.85 mmol.l-1, from a pre-treatment concentration of 7.4 mmol.l-1 to a treatment value of 6.5 mmol.l-1, and LDL-cholesterol fell by 0.64 mmol.l-1, from 5.5 mmol.l-1 to a treatment value of 4.8 mmol.l-1. There was no significant change in triglyceride and VLDL concentrations during the study. A slight but significant fall in HDL-cholesterol was seen. The sole adverse effect was occasional intestinal discomfort.