Water potential receptors in the skin regulate blood perfusion in the ventral pelvic patch of toads.

Blood cell flux (BCF) in ventral pelvic skin capillaries was measured in conscious unrestrained Bufo bufo, using a laser Doppler flowcytometer. Hydrated toads responded to water contact with a small but significant increase in BCF. Dehydration alone did not change the BCF in seat patch skin before water contact. However, water contact by dehydrated toads elicited a rapid 600% increase in BCF. The BCF and water uptake of dehydrated toads rehydrating in water declined over 2 h but remained significantly above the low, constant values measured in hydrated toads. Arginine vasotocin injection in hydrated toads did not change skin BCF, but water uptake increased, and urine production decreased. Injection of the beta -adrenergic agonist isoproterenol increased BCF in hydrated toads by 900% and also increased the rate of water uptake. These increases corresponded in magnitude and duration to the response to water contact observed in dehydrated toads. Injection of dehydrated toads with the beta -adrenergic antagonist propranolol significantly reduced both BCF and water uptake. These results are consistent with an autonomic reflex mediated by skin water potential receptors that regulate blood perfusion of ventral pelvic skin.

Angiotensin II elicits water seeking behavior and the water absorption response in the toad Bufo bufo.

Fully hydrated toads, Bufo bufo were acclimated to a simulated terrestrial habitat, with access to shelters and water. To get from the shelters to the water, the toads had to walk across the pan of an Ohaus balance and the body weights were recorded on a computer. Toads were placed inside shelters immediately following injection of human angiotensin II (A II), Thr(8)-saralasin, or Ringer's in the dorsal lymph sac, and their behavior was recorded continuously by video surveillance. The injection doses were 1-100 microg/100 g body weight A II and 100 microg/100 g body weight saralasin dissolved in 0.1 ml Ringer's; control animals received the same volume of Ringer's. The latency from injection to the initiation of water absorption behavior (WR) was significantly shorter in both A-II- and saralasin-injected toads, compared to controls. A-II- and saralasin-injected toads also spent significantly more time in the water than controls. The bladder depots when WR was terminated were significantly larger in A-II- or saralasin-injected toads than in controls. The stimulatory action of Thr(8)-saralasin, an antagonist of A II in mammals, on WR behavior in B. bufo suggests differences in receptor structure and/or receptor distribution between amphibians and mammals.

Physiological and endocrinological responses during prolonged exercise in hatchery-reared rainbow trout (Oncorhynchus mykiss).

Rainbow trout (Oncorhynchus mykiss) were subjected to vigorous exercise (1.5 body length s-1), low exercise (0.5 body length s-1) or still-water (0.0 body length s-1). Hematocrit, glucose, growth hormone (GH), cortisol and triiodo-L-thyronine (T3) were monitored at the start of exercise, after 24 h, and after 2, 4, 8, 16 and 32 days of continuous swimming. Morphological indices and food intake were also monitored. At the end of the experiment, trout subjected to low exercise had gained significantly (p < 0.05) more weight than both the control (still-water) and vigorously exercised fish. This low exercised group of fish also consumed more food than the 2 other groups. Hematocrit increased significantly in both exercised groups at the onset of swimming but returned to pre-exercise levels within 8 hrs. Plasma glucose appeared to be generally unaffected by exercise. Likewise, plasma concentrations of both GH and T3 were not influenced by exercise. Plasma cortisol levels increased in an exercise dependent fashion at the onset of swimming, but returned to pre-swimming levels within 24 h and there was no apparent effect of sustained swimming. The results suggest: (i) the onset of exercise elicits transient changes in plasma components, (ii) the observed weight gain in low exercising salmonids occur without increases in circulating levels of GH or T3.

The prevalence and etiology of impotence in 101 male hypertensive outpatients.

Erectile dysfunction and impotence has a high prevalence among male hypertensive patients. Whether this relates mainly to specific drug side effects or to primary pathogenic disorders is unknown. In the present study 101 male patients from our outpatient hypertension clinic answered detailed questionnaires about hypertension and sexual function. Patients with perceived impotence were offered a thorough penile evaluation and examination performed by specialists in the urology department. Twenty-seven (27%) men had impotence. The main cause of impotence was an arterial dysfunction (89%). The prevalence of impotence was related to the degree of secondary organ manifestation, reflected by World Health Organization (WHO) classification I-III (P = .01). Intermittent claudication (P = .001) and ischemic heart disease (P = .005) were the best determinants in this respect. Twelve impotent patients (44%) ascribed onset of impotence to drug initiation. A variety of drugs were incriminated in the occurrence of drug-induced impotence. In summary our results indicate that impotence in hypertensive men is caused mainly by penile arterial vascular changes, probably atherosclerosis. Drug-induced impotence could well be the result of blood pressure reduction itself and not specific drug side effects.

Cu uptake, metabolism and elimination in fed and starved European eels (Anguilla anguilla) during adaptation to water-borne Cu exposure.

64Cu accumulation and total Cu concentrations were measured in gill filaments, plasma, liver and bile of fed and starved European eels (Anguilla anguilla) during 28 days of exposure to 12 and 94 micrograms Cu l-1. Branchial Cu uptake was found to be 0.03 and 0.13 microgram Cu g gill filament-1 h-1 at 12 and 94 micrograms Cu l-1, respectively, throughout 28 days of Cu exposure. At least during exposure to 94 micrograms Cu l-1, the basolateral membrane seemed to be the rate limiting step for branchial Cu uptake. The plasma accounted for at least 70% of the 64Cu labelled Cu present in the blood at both Cu concentrations. The plasma Cu concentration was gradually increased from 0.64 to 1.92 and 2.68 micrograms ml-1 during the first 6 days of Cu exposure; it was partly normalized to 1.07 and 1.45 micrograms ml-1 after 28 days of exposure to 12 and 94 micrograms Cu l-1, respectively, despite a constant branchial Cu uptake, indicating an increased turnover of plasma Cu. The hepatic accumulation of 64Cu was similar in fed and starved eels (0.55 microgram Cu g liver-1 h-1) at both Cu concentrations during the 28 days of exposure. The hepatic total Cu concentrations were lower in the fed fish compared to the starved fish and increased only marginally from 3 to 28 days of exposure indicating a high turnover of hepatic Cu during acclimation. Hepatic Cu elimination, measured as 64Cu in the bile, was highest in the fed fish at the highest Cu concentration and was stimulated during acclimation at least in the starved fish.

Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer: DAPROCA study 9002. Danish Prostatic Cancer Group.

PURPOSE: We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer. MATERIALS AND METHODS: In a double-blind multicenter study 131 patients with progressing metastatic hormone refractory prostate cancer were randomized to receive 280 mg. estramustine phosphate 2 times daily versus placebo. End points were clinical progression and death. Adverse events, decrease in prostate specific antigen (PSA) and subjective response were also assessed. RESULTS: Adverse events were common in both groups but breast tenderness/gynecomastia and diarrhea were more frequent among patients in the estramustine phosphate group. Subjective responses were few (9 of 50 estramustine phosphate and 4 of 57 placebo cases, p = 0.15). Median observation time for survival was 43 months and 124 patients died. Median time to subjective progression and median overall survival did not differ significantly between the 2 groups at 4.6 and 9.4 months in the estramustine phosphate group versus 5.0 and 6.1 months in the placebo group. Of 61 patients in the estramustine phosphate group 29 achieved a reduction in PSA of more than 25% at 1 month of followup compared to only 3 of 68 receiving placebo. A decrease in PSA after 1 month correlated significantly with survival. CONCLUSIONS: Although this study did not prove estramustine phosphate to be superior to placebo in terms of protocol end points, it generates the hypothesis that prolonged survival may be achieved with estramustine phosphate treatment in a subgroup of patients and that this may be predicted by a decrease in PSA after 1 month of therapy.

What mechanisms control neoteny and regulate induced metamorphosis in urodeles?

The Mexican axolotl, like a number of other urodele species, is an obligatory neotene, completing its full life cycle without metamorphosis. Metamorphosis can be induced with thyroid hormone, thyroid stimulating hormone, or stimulation of hypothalamic neurons. Thus, neoteny represents a deviation from the standard course of amphibian ontogeny, affecting the thyroid axis at one or more levels. Analysis of the thyroid axis at strategic ontogenic stages and after completed neotenic development suggests that there are a number of deviations, and that the deviations may be temporal and/or quantitative in nature. A surge of thyroxine secretion occurs early in larval life but does not lead to metamorphosis, apparently because the enzyme which deiodinates thyroxine to the active form, triiodothyronine, is not yet present. Later in ontogeny, activity in the thyroid axis is low. Hormone treatment can reactivate the thyroid axis at all levels, but some singularities remain. Inhibition at central nervous or peripheral levels may be involved in axolotl neoteny.

Residual urine in 75-year-old men and women. A normative population study.

The prevalence of residual urine in elderly people in the community is poorly documented. The aim of the present study was to assess the prevalence and range of residual urine in elderly people in the community. As part of a major epidemiologic study (The Glostrup Population Study), 140 75-year-old men and women were included in this study (92 men, 48 women). All were selected at random from the Central Person Register by age and residence. All had a single sonographic measurement of residual urine with a prevoid volume of 150 ml or more. More than 10 ml of residual urine was found in 91 of the 92 men (median 90 ml; range 10-1502 ml), and in 44 of the 48 women (median 45 ml; range 0-180 ml). Our figures correspond to those previously reported in selected patient populations. It must be emphasized, however, that our findings are merely descriptive, as the clinical significance of a single residual urine determination is questionable.

Effect of induced metamorphosis on the immune system of the axolotl, Ambystoma mexicanum.

Metamorphosis was induced in neotenic axolotls by immersion of the animals in a solution of thyroid hormone. Hematology of the axolotls was examined before, during, and after metamorphosis. There was a transient decrease in numbers of certain white blood cells during metamorphic climax and a permanent shift in the pattern of circulating cells. The eosinophilic granulocyte was the dominating leukocyte type in neotenes and in metamorphosing animals up to midclimax. Lymphocytes and neutrophilic granulocytes (polymorphs) significantly decreased during midclimax. In postmetamorphic axolotls, lymphocytes and polymorphs predominated. The observed decrease of some leukocytes in metamorphosing animals accords with a transient immunosuppression at metamorphic climax. Metamorphosed axolotls showed a humoral immune response (increase in circulating plasma cells) after repeated antigen challenge, whereas neotenic axolotls did not. Alterations in both cellular and humoral immunity are suggested to occur in both young and adult axolotls following experimental induction of metamorphosis.

Nocturnal enuresis: change of nocturnal voiding pattern during alarm treatment.

In a prospective clinical study of the outcome of alarm treatment in nocturnal enuretics, 60 children were included: 40 boys and 20 girls, mean age 8.2 years (range 5.1-14.4). All were treated with enuresis alarms and had 2 or more enuretic events during the initial 14 days of treatment. None had diurnal enuresis. In each child, the enuretic and voluntary voiding frequencies during the initial 14 and last 14 days of treatment were compared. We found that 43 children had a 75% reduction or more of the enuretic events. 28 children substituted the former enuretic events by sleep, 15 changed the enuresis by voluntary voidings. Only 17 children had no effect of the alarm treatment. No parameters were found to predict the outcome. In conclusion, the outcome of successful alarm treatment occurs in two distinct forms. Either the child is left asleep without wetting his bed; or the child wakes up spontaneously from sleep and goes to the bathroom.

Water-balance response to salt loads in the toad Bufo bufo: independence of hypophysial pars nervosa function.

1. In water, injection of 1 ml of 1 mol/l NaCl/100 g body mass increased the rates of cutaneous water uptake and reduced the rates of bladder urine accumulation both in unoperated and sham operated controls and in toads with denervated or extirpated neuro-intermediate lobe. 2. This initial antidiuretic effect of the salt load gradually changed to a diuretic effect, when the volume expansion caused by cutaneous water uptake overrode the effect of increased osmolarity. 3. In a saturated atmosphere, injections of 0.3 or 0.5 ml of 0.7 mol/l NaCl/toad (mean body mass 33 g) reduced urine accumulation. Only to the largest load was the antidiuretic response significantly smaller in the toads with denervated or extirpated neuro-intermediate lobe. 4. It is argued that the reduced antidiuretic response was due to interference with pars distalis function rather than caused by lack of pars nervosa function.

Non-invasive management of impotence with transcutaneous nitroglycerin.

Nitroglycerin plasters were applied to the penis in 10 impotent men and the erectile effect assessed. During laboratory testing all patients achieved an erectile response. Self-administration of nitroglycerin patches restored potency in 4 patients and was preferred to papaverine auto-injection by 3. Headache was a common side effect during initial administration. An attempt to treat impotence with nitroglycerin plaster seems worthwhile before starting extensive investigations or invasive treatment.

Late complications of Prostakath treatment for benign prostatic hypertrophy.

The self-retaining intra-urethral device "Prostakath" was inserted in a consecutive series of 29 men with obstructive benign prostatic hypertrophy. Fifteen patients were relieved of prostatic symptoms for an observation period of 22 weeks (range 2-60). The spiral was removed in 14 cases (48%) at an average of 14 weeks (range 1-82) after insertion; in 9 patients this was because of urinary retention and in 5 it followed dislocation of the stent into the bladder. Five stents removed after 44 weeks of treatment (range 21-82) were severely calcified. Light microscopic investigation of the Spirals that were removed revealed no damage to the gold-plated surface. All patients with calcification had chronic urinary infection resistant to antibiotic treatment. We believe that infected urine is the major factor responsible for the calcification. We suggest that patients with recurrent urinary infection after insertion of the Prostakath should be closely followed up and checked for stone formation by a plain X-ray of the bladder region. It may be advisable to change the Prostakath in patients with resistant urinary tract infection at 6-monthly intervals.

Erectile dysfunction following direct vision internal urethrotomy.

A total of 104 evaluable patients 20-90 years old treated by direct vision internal urethrotomy a.m. Sachse for urethral strictures reported retrospectively via a questionnaire their sexual potency before and after internal urethrotomy. Eleven patients (10.6%) experienced partial or total erectile dysfunction following the operation, most of whom had distal and long strictures. Eight were evaluated for impotence and on grounds of a comprehensive history, physical examination, penile Doppler investigations, and papaverine tests it was concluded that 3 patients might have achieved an abnormal communication between the corpus cavernosum and corpus spongiosum. In two of the patients cavernosographies were carried out and in one total opacification of the corpus spongiosum was demonstrated, but the exact location of the leak could not be pinpointed, and surgical treatment therefore not rendered feasible. Possible factors in the development of erectile dysfunction following internal urethrotomy are analyzed.

Measurement of renal function with iohexol. A comparison of iohexol, 99mTc-DTPA, and 51Cr-EDTA clearance.

The nonionic iodinated contrast medium, iohexol, introduced for clinical urography, is eliminated from the human organism mainly by glomerular filtration. The aim of this study was to analyze the applicability of iohexol for glomerular filtration rate (GFR) measurement by comparing the plasma clearance of iohexol to the plasma clearance of the traditionally employed substances, chromium-51-EDTA and technetium-99m-DTPA. Iohexol concentration was measured by x-ray fluorescence. To analyze for possible acute effect of iohexol on renal function, additional measurements of 99mTc-DTPA clearance were made prior to the injection of iohexol. In 15 patients having clearance values between 30 and 130 ml/min per 1.73 m2, there were close correlations (r = 0.95-0.98) among iohexol, 51Cr-EDTA, and 99mTc-DTPA clearance. No significant acute renal effect of iohexol was demonstrated. It is concluded that measurement of iohexol clearance provides information about GFR that is as valid as measurements of 51Cr-EDTA and 99mTc-DTPA clearance. Thus, it is possible to perform urography and a determination of GFR using a single injection of iohexol.

Laser treatment of recurrent urethral condylomata acuminata in men.

Fifty-six consecutive men with recurrent condylomata acuminata of the urethra and possibly also of the external genitalia were treated with carbon dioxide or ND: YAG laser or both. In all patients previous conservative treatments had failed. Half the patients responded completely to a single treatment and 86% to a maximum of three treatments. No important side effects were encountered, and the cosmetic results have been excellent.

Pad-weighing test performed with standardized bladder volume.

The result of the one-hour pad-weighing test proposed by the International Continence Society has been demonstrated to depend on the urine load during the test. To increase reproducibility of the pad-weighing test by minimizing the influence of variation in urine load the test was done with a standardized bladder volume (50% of the cystometric bladder capacity). Twenty-five female patients with stress or mixed incontinence underwent two separate tests. Test-retest results were highly correlated (r = 0.97, p less than 0.001). Nonetheless, analysis of test-retest differences revealed a variation up to +/- 24 g between two tests. It is concluded that this setup (i.e., standardized bladder volume) of the one-hour pad-weighing test allows for a more reliable assessment of urinary incontinence for quantitative purposes.

Transurethral surgery in the treatment of invasive bladder cancer (T1 and T2).

Ninety-nine primary transitional cell bladder tumours of categories T1 or T2 were treated by transurethral resection. 25% of these patients experienced a true recurrence indicating that surgery failed to control the tumour locally. These patients had a 5-year survival of 20%. We suspect that many of them did not have local disease when treated. Twenty-five % of the total patient population did not within five years get a new tumour. They were cured by the first transurethral resection. 30% of the patients experienced new non-invasive tumour growth that could be managed by repeated resections. These two groups of patients did extremely well, since the 5-year survival was equivalent to the 5-year survival of an age and sex matched control population. Thus, more than 50% of the patients benefitted from transurethral surgery. Less than 20% experienced a new invasive tumour growth. They are patients at risk of getting a progressive bladder cancer disease. 5-year survival of these patients was about 50%. We conclude that transitional cell bladder tumours of category T1 and some of category T2 are well treated by transurethral resection.