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Rainbow trout (Oncorhynchus mykiss) males were fed, during a 9-month period, five experimental diets where fishmeal proteins were gradually replaced with cottonseed meal (CS) proteins (0, 25, 50, 75 and 100%; diets 1–5, respectively). This study was carried out to evaluate the action and tissue concentrations of gossypol. Growth performance of fish was not affected with the increasing levels of CS in the diets. Haemoglobin concentration and haematocrit significantly decreased in fish fed 100% CS compared with other dietary treatments. Gonadosomatic index, plasma sex steroids (testosterone, 11-ketotestosterone and 17,20β-dihydroxy-4-pregnen-3-one) and sperm characteristics (concentration, motility, protein concentration and lactate dehydrogenase activity) were not negatively affected by increasing levels of CS. For the first time, a comprehensive study of gossypol concentrations, total and (+) and (−)-enantiomers, in several tissues (liver, blood plasma, spermatozoa and seminal plasma) was performed. The concentrations of both (+) and (−)-enantiomers significantly increased with increasing levels of CS in the diet. The highest concentrations were found in the liver of fish fed diet 5 (185 ± 18 μg g−1). In blood plasma, the concentrations of total gossypol were 10 times lower than the one found in the liver, but 10 and 100 times higher than the concentrations in the spermatozoa and seminal plasma, respectively. In all tissues studied, the concentration of (+)-enantiomer was higher than the (−)-enantiomer. The ratio (−)-enantiomer/total gossypol did not change significantly with the increasing levels of CS in the diet. The results of the present study indicate that CS can be used over a period of 9 months to replace fishmeal proteins completely without compromising growth and reproduction of rainbow trout males.

A mixture of animal by-products (MAB) was tested to replace fish meal (FM) in diets for juvenile rainbow trout Oncorhynchus mykiss. Fish averaging (±SD) 0.96 ± 0.07 g were divided into 15 groups, and 3 groups were fed one of five isonitrogenous diets replacing 0, 20, 40, 60, or 100% of FM protein with similar percentages of MAB (control, MAB20, MAB40, MAB60, or MAB100, respectively). The MAB consisted of 25% meat and bone meal, 24.5% leather meal, 20% squid liver powder, 15% feather meal, 7.5% blood meal (spray-dried), 7.5% poultry by-product meal, and 0.25% each methionine and lysine. After 16 weeks of feeding, fish fed diets MAB40, MAB60, and MAB100 exhibited significantly lower growth performance than the fish fed the control and MAB20 diets. Apparent digestibility estimates of protein with different collection times (every 40 min and after 12 and 48 h) did not show, in a feces collection system, protein leaching into the water for up to 48 h. The MAB substitution of up to 60% of FM protein in...

We evaluated five practical diets in which 0%, 25%, 50%, 75%, and 100% (dietary treatments 1‐5) of fish meal protein was replaced by solvent-extracted cottonseed meal protein. Adult rainbow trout (initial average weight 247 6 8 g) were fed the diets over a period of 131 days during which a general 2fold body weight increase occurred. The total diet gossypol concentration (free and protein-bound) showed a gradual increase with increased cottonseed meal substitution. Blood samples were collected on Days 0, 64, 112, and 131 for hematological and steroid hormone determination in plasma of males and females. Hemoglobin content was significantly reduced in fish from treatment 5 (7.9 6 0.3 g/dl) in comparison to treatments 1‐3 (10.3‐10.9 g/dl). After 112 and 131 days of feeding, testis weights, concentrations of testosterone, and 11-ketotestosterone were elevated in fish from dietary treatments 2 and 3 in comparison to control and diets 4 and 5. On Day 71, sperm were collected from 6 fish per dietary treatment to assess sperm quality. No significant differences in sperm concentrations (7.2‐9.8 3 10 9 /ml), motility (78‐89%), and standardized (300 3 10 5 sperm/egg) fertilizing ability (18.9‐22.6% hatched embryos) were found. Total gossypol concentrations in blood plasma differed significantly among treatments, and the levels were among the highest ever recorded in animals fed cottonseed-supplemented diets (2.9 6 0.2, 11.7 6 4.1, 21.7 6 1.4, and 29.9 6 3.9 mg/ml, for treatments 2‐5, respectively). The major portion of gossypol in blood plasma was protein-bound (81‐93%). This was in contrast to minute amounts of gossypol present in seminal plasma, mostly in free form (0.02‐0.18 mg/ml), which indicates the presence of a barrier between general circulation and the testis with respect to gossypol distribution in lower vertebrates. Thus, the reproductive parameters of male rainbow trout examined in this study were not significantly affected by feeding cottonseed meal for 131 days.

Ascorbic acid is an essential nutrient in rainbow trout diets and has been shown to play an important role in fish reproduction. Recommended dietary levels are based on immature fish, and the specific requirements for brood stock are unknown. To establish the optimum dietary level for mature rainbow trout, six graded levels of ascorbyl-2-monophosphate were fed to groups of female fish over a period of 10 mo until spawning. Increasing dietary levels of ascorbyl monophosphate resulted in significantly increased ascorbic acid concentrations in liver, kidney, ovaries, and ovulated eggs. Liver and egg concentrations were saturable at 109.3 and 266.6 micrograms ascorbic acid/g tissue, respectively. Tissue saturation levels of 83.7% and 91.2%, respectively, were reached at the highest dietary level (870 mg ascorbyl monophosphate/kg diet) tested. Both fecundity and embryo survival increased significantly with dietary ascorbyl monophosphate levels. The results indicated that the present National Research Council recommended dietary level of 50 mg ascorbic acid/kg diet for rainbow trout is inadequate for brood stock fish. An amount 8 times higher is necessary to optimize tissue ascorbic acid levels and achieve maximum reproductive success.

Diets incorporating three different sources of extracted cottonseed meal (CM), soybean meal and an animal protein mixture were evaluated for juvenile rainbow trout. Fish averaging 0.96 g were divided into groups of 30; 3 groups per treatment, and each group was fed one of four diets for a 16-week period. Fish meal (FM) was replaced on a 25% protein basis by each of three different sources of CM from California (CA), Tennessee (TN), and Arkansas (AR), U.S.A. In the three CM-containing diets another 25% soybean meal protein and 50% animal protein mixture were also incorporated to completely replace FM protein. The results of growth rate and feed utilization showed that FM could be entirely replaced by a mixture of plant proteins (CM and soybean meal) and animal by-product proteins. Hematocrit levels were significantly lower in the group fed CM-containing diets than in the control. The findings suggest that CM can be used as a good protein source by the incorporation of at least 15% in diets (25% of fish meal protein replacement), and that the nutritive values of CM in juvenile trout can be different due to their different origin. Significantly higher concentrations of total gossypol were found in faeces of CM-TN (5.8 +/- 0.4 micromol/g) and CM-AR (5.6 +/- 0.6) groups than in that of CM-CA (3.7 +/- 0.4) group. It was documented that gossypol enantiomers, present in an equal proportion in diets, selectively accumulated in liver and bile, whereas equal proportions of (+)- and (-)-enantiomers were found in whole-body and faeces. Depending on CM source, fish can absorb approximately 35-50% of dietary gossypol, and the majority of the absorbed gossypol seemed to be excreted.

We investigated the role of gossypol isomers binding to blood plasma, seminal plasma and spermatozoa to elucidate gossypol anti-fertility action in the teleost fish, rainbow trout (Oncorhynchus mykiss). Growth and hematological indicators of males were depressed when fish meal protein in diets was completely replaced with cottonseed meal. The cottonseed meal contained equal proportions of (-) (47.8+/-1.6%) and (+) gossypol isomers. Concentrations of spermatozoa were decreased with increasing proportions of gossypol in diets (from 0.22% to 0.95%); however, sperm motility and fertilizing ability were not affected. In contrast to mammals, steroid hormone concentrations were not suppressed in fish given diets with gradual increase of gossypol level. Gossypol concentrations were 100-fold higher in blood plasma than in seminal plasma, confirming a barrier in gossypol transfer between the general circulation and the testis. Spermatozoa accumulated predominantly (+) enantiomer (65-75%) with decreasing proportions as dietary gossypol concentrations increased. Spermatozoa bound most of the gossypol contained in the semen; however, this did not result in impairment of the sperm motility apparatus. Teleost fish sperm rely on ATP stores that accumulate during maturation as a source of energy during activation. In addition, the duration of sperm movement is short in these fish. As such, we hypothesize that the major action of gossypol on mammalian sperm, which is uncoupling of oxidative phosphorylation, does not impair the energy supply required for flagellar beating in fish spermatozoa.

We evaluated five practical diets in which 0%, 25%, 50%, 75%, and 100% (dietary treatments 1-5) of fish meal protein was replaced by solvent-extracted cottonseed meal protein. Adult rainbow trout (initial average weight 247 +/- 8 g) were fed the diets over a period of 131 days during which a general 2-fold body weight increase occurred. The total diet gossypol concentration (free and protein-bound) showed a gradual increase with increased cottonseed meal substitution. Blood samples were collected on Days 0, 64, 112, and 131 for hematological and steroid hormone determination in plasma of males and females. Hemoglobin content was significantly reduced in fish from treatment 5 (7.9 +/- 0.3 g/dl) in comparison to treatments 1-3 (10.3-10.9 g/dl). After 112 and 131 days of feeding, testis weights, concentrations of testosterone, and 11-ketotestosterone were elevated in fish from dietary treatments 2 and 3 in comparison to control and diets 4 and 5. On Day 71, sperm were collected from 6 fish per dietary treatment to assess sperm quality. No significant differences in sperm concentrations (7.2-9.8 x 10(9)/ml), motility (78-89%), and standardized (300 x 10(5) sperm/egg) fertilizing ability (18.9-22.6% hatched embryos) were found. Total gossypol concentrations in blood plasma differed significantly among treatments, and the levels were among the highest ever recorded in animals fed cottonseed-supplemented diets (2.9 +/- 0.2, 11.7 +/- 4.1, 21.7 +/- 1.4, and 29.9 +/- 3.9 microg/ml, for treatments 2-5, respectively). The major portion of gossypol in blood plasma was protein-bound (81-93%). This was in contrast to minute amounts of gossypol present in seminal plasma, mostly in free form (0.02-0.18 microg/ml), which indicates the presence of a barrier between general circulation and the testis with respect to gossypol distribution in lower vertebrates. Thus, the reproductive parameters of male rainbow trout examined in this study were not significantly affected by feeding cottonseed meal for 131 days.

The authors present demographic and surgical data from a randomized phase III trial, instituted by the EORTC Genitourinary Group in 1988, the aim of which was to assess whether complete lymph node dissection in conjunction with radical nephrectomy for renal cell cancer is more effective than radical nephrectomy alone.Before surgery, the renal cell carcinoma was staged and judged to be nonmetastatic and resectable. The patients were randomized prior to surgery into those having radical nephrectomy combined with complete lymph node dissection or into those having radical nephrectomy alone. Postoperatively all patients were followed until progression of disease or death.Of the 772 randomized patients, 41 were not eligible. 383 had a complete lymph node dissection together with a radical nephrectomy. 389 had a radical nephrectomy alone. The complication rate did not differ significantly between the two groups. A complete lymph node dissection in 336 patients revealed absence of lymph node metastases in 325 of them.The present study shows that complete lymph node dissection does not add morbidity to the radical nephrectomy. After proper preoperative staging, the incidence of unsuspected lymph node metastases is low (3.3%).

In scurvy-prone animals ascorbic acid uptake is regulated by the number of intestinal "brush-border" carriers available for transport. The number of carriers is negatively affected by an increasing dietary ascorbic acid intake, thus limiting the maximum attainable uptake. We tested a new approach towards manipulating the accumulation of ascorbic acid in rainbow trout by repeatedly feeding a 10 day ascorbic acid allowance in a 1 or 3 day "pulse" followed by withdrawal, rather than spread out over the entire 10 day period. Pulse dosing led to initially increased mortalities compared to continuous dosing, but this was reversed after 55 days. Although individual weight and cumulative mortality were not significantly different after 88 days, total liver ascorbic acid levels were significantly higher in the 1-day pulse group (16.3 +/- 3.9 micrograms/g) than in the 3-day pulse (9.8 +/- 0.9 micrograms/g) or continuous (9.3 +/- 0.9 micrograms/g) groups. This led us to conclude that after an initial adaptation phase a feeding profile with intermittent ascorbic acid withdrawal results in a compensatory increase in uptake of ascorbic acid from the diet and/or a better conservation of the body pool of ascorbic acid, opening interesting new avenues for ascorbic acid dosing and therapy.

Ascorbic acid is an essential nutrient in rainbow trout diets and has been shown to play an important role in fish reproduction. Recommended dietary levels are based on immature fish, and the specific requirements for brood stock are unknown. To establish the optimum dietary level for mature rainbow trout, six graded levels of ascorbyl-2-monophosphate were fed to groups of female fish over a period of 10 mo until spawning. Increasing dietary levels of ascorbyl monophosphate resulted in significantly increased ascorbic acid concentrations in liver, kidney, ovaries, and ovulated eggs. Liver and egg concentrations were saturable at 109.3 and 266.6 micrograms ascorbic acid/g tissue, respectively. Tissue saturation levels of 83.7% and 91.2%, respectively, were reached at the highest dietary level (870 mg ascorbyl monophosphate/kg diet) tested. Both fecundity and embryo survival increased significantly with dietary ascorbyl monophosphate levels. The results indicated that the present National Research Council recommended dietary level of 50 mg ascorbic acid/kg diet for rainbow trout is inadequate for brood stock fish. An amount 8 times higher is necessary to optimize tissue ascorbic acid levels and achieve maximum reproductive success.

Two-year old rainbow trout females were fed diets containing 0, 30, 110, 220, 440 and 870 mg kg-1 ascorbyl-2-monophosphate Mg+ salt (groups 1, 2, 3, 4, 5, and 6, respectively) from August until March. At the time of spawning (February–March) blood was sampled and the ovulating females were hand stripped. Estradiol (E2) and testosterone (T) concentrations in plasma, and ascorbic acid (AA) concentrations in plasma and eggs were determined. The mean plasma concentrations of T were higher in group 4, 5, or 6 than in group 2 or 3 (p < 0.05). Moreover, the average plasma concentration of T in fish fed the diets with AA level below National Research Council (NRC) recommendations (groups 1, 2 and 3) was significantly lower (p

We studied 98 patients with locally confined but lymph node positive prostatic cancer (1 stage T1, 29 stage T2, 55 stage T3 and 2 stage T4) who were not treated by radical prostatectomy. A retrospective analysis was done of deoxyribonucleic acid (DNA) ploidy of pretreatment core biopsies of the primary tumor and lymph node metastases. While DNA ploidy has been shown to be an important prognostic factor if applied to radical prostatectomy specimens, core biopsy specimens and nodal metastases have rarely been studied. Of the 98 patients 87 were evaluable for DNA ploidy: 45 (52%) had diploid, 13 (15%) had tetraploid and 29 (33%) had aneuploid tumors. The ploidy of the primary tumor and of the lymph node metastases correlated significantly with the rate of progression and interval to progression. Also, significant correlations were noted between the percentages of cells in the S phase or S plus G2 phases of the cell cycle and interval to progression. Most patients in this study are part of the European Organization for Research and Treatment of Cancer protocol 30846, a prospective randomized study of early versus delayed treatment in lymph node positive, otherwise locally confined prostate cancer. This study is ongoing. Early endocrine treatment was associated with a significantly longer interval to progression. In a Cox regression analysis of the prognostic factors involved in this study, early endocrine treatment was more important than ploidy or proliferation patterns. Stage (T category) and histopathological grade did not show a correlation with progression. Followup is still too short and the numbers of patients are too small for relevant subgroup analysis. DNA ploidy measurement by flow cytometry on archival (paraffin embedded) core biopsy and lymph node material is possible, and produces meaningful results in predicting the prognosis of prostatic cancer. Since this information can be made available before treatment decisions, its exact value in the management of locally confined prostate cancer can be determined.

In a phase II study, 24 patients with metastatic prostatic cancer were treated with mitomycin C 15 mg/m2 i.v. every 6 weeks, combined with aminoglutethimide 250 mg twice a day. A low dose of 37.5 mg cortisone acetate was supplied daily to compensate for adrenal cortical suppression. A partial response was demonstrated in 4 of 24 evaluable patients with bi-dimensionally measurable metastases. Stable disease occurred in 8 patients over a period of more than 6 months. Within the maximum cumulative dose limit of 2 mg/kg body weight mitomycin C, toxicity was observed in 21 cases, including 2 deaths due to treatment toxicity. The poor response rate and high toxicity suggest that the addition of aminoglutethimide does not enhance the effect of mitomycin C in these patients.

Benign prostatic hyperplasia (BPH) is a frequent condition in men over 50 years of age. At autopsy the histological characteristics of BPH are seen in 80% of all men older than 80 years. Although BPH is so frequent, its precise etiology is still unknown. Each of the various sources from which epidemiological data on BPH can be obtained has its own specific problems in terms of potential errors and biases, which have to be taken into account in interpretation of the data from these sources. There are clear differences in the incidence of BPH in various races. In negroids BPH is more frequent than in Caucasians, while in Asiatic races BPH is less frequent. However, in Asiatics BPH occurs more frequently in men who have immigrated into western countries. Age and hormonal status are well known to be involved in the development of BPH. Other factors, such as marital status, socioeconomic class, smoking, diet, diabetes, hypertension, and liver cir-rhosis have been implicated, but their relation with the risk of developing BPH has never been proven. The natural history of BPH is characterized by an age-dependent increase in histological changes and an increase in prostate size. The histological changes compatible with BPH are found in men below the age of 30 with an incidence of less than 10%. During the 6th decade, 42% of prostatic specimens have histological signs of BPH and during the 8th decade of life more than 80% of prostatic specimens. The histological changes of BPH precede prostatic enlargement by roughly 1 decade. There is an initial spurt of prostate growth during the period of maturation and puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

The case is discussed of a patient with renal insufficiency due to severe stenosis of both ureters brought about by a periaortic inflammatory process. Such periaortitis is seen in severe atherosclerosis; the condition allegedly occurs in 5 to 23% of all patients with an abdominal aortic aneurysm. The literature on this form of retroperitoneal fibrosis is reviewed.

Airline pilots with a mild to moderate hearing loss are regularly examined in the Netherlands National Aerospace Medical Centre. If this hearing loss exceeds the national hearing standards not only a tone-audiometric test but also routine speech-audiometry is performed. The maximal discrimination of phonetically balanced monosyllable words (20 word lists) in 16 airline pilots (32 ears) with such a hearing loss varies between 65%-100%. However, none of these pilots complains of a bad speech-intelligibility in the cockpit. This may indicate that there is a poor relation between the routine speech discrimination and the speech intelligibility in the working situation. We developed a "speech-audiometric" test (RT-test) which is completely based on the aviation jargon used in radiotelephony (RT) communications. In our group of 16 pilots the maximal discrimination in the RT-test was excellent. Even for ears with a maximal discrimination of 65%-70% in the routine speech-audiometric test the maximal RT-discrimination was 99%-100%. These pilots were all very experienced (average: 14,360 flying hours). Undoubtedly, this experience is of great importance in radiotelephony-intelligibility.

In a preceding study, complete substitution of fish meal protein with cottonseed meal (CM) protein did not affect the survival or growth rate of adult rainbow trout over a 6-mo period. Gossypol, a naturally occurring compound in cottonseeds, has an antifertility effect in terrestrial animals, but information regarding salmonid fish is lacking. Female rainbow trout in this experiment were fed diets with either 0, 25, 50, 75, or 100% (diets 1 to 5) of the fish meal protein replaced with CM protein until first maturation and spawning to study long-term effects on growth and reproduction. Feeding diets containing CM over a total period of 10 mo did not result in differences in growth and mortality compared to the control group (P0.05). Increased CM incorporation levels resulted in decreased (P0.05) blood hemoglobin (10.6 +/- 1.3, 8.4 +/- 1.8, 7.3 +/- 1.1, 6.9 +/- 0.8, and 5.6 +/- 1.4 g/dL) and hematocrit (49.6 +/- 3.9, 38.5 +/- 9.3, 34.4 +/- 3.7, 34.8 +/- 4.9 and 28.0 +/- 6.8%) levels in diets 1 to 5, respectively. The CM incorporation level had no effect (P0.05) on the number of eggs produced per female but led to a reduction (P0.05) in egg weight. Eyed stage survival of embryos was low in all dietary groups and did not show differences (P0.05). However, an increasing CM incorporation level led to a linear increase (P0.05) in the number of females that produced no viable embryos (23.1, 37.5, 42.9, 60.0, and 71.4%). Gossypol in the diet was absorbed by the female trout and transferred to the eggs (0, 2.2 +/- 0.5, 6.7 +/- 1.6, 10.6 +/- 4.2, and 20.0 +/- 2.6 micrograms/g in diets 1 to 5, respectively). A high concentration of gossypol remained in the juveniles at the swim-up stage (endogenous yolk-absorbed) (0.6 +/- 0.3, 2.4 +/- 0.3, 3.4 +/- 0.0, and 4.7 +/- 1.0 micrograms/g, diets 2 to 5, respectively). The findings suggest that replacement of the dietary fish meal protein with CM protein has no effect on fish growth and mortality but may lead to a reduction in reproductive performance in female rainbow trout.

A simple double-discharge electrode arrangement for the cw excitation of supersonic molecular gas flows is described. Stable discharges in N2 and N2/CO mixtures, with E/N of 2.0-2.5×10-16 V cm2 and a power loading of 2.6×10-2 eV/molecule, were achieved.