Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries

 Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM and 1000 nM ANG II increased NO-oxidation current by 85±18 pA (n = 11), 148±22 pA (n = 11), and 193±29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4±0.5 nM, 6.1±1.1 nM, and 8.2±1.3 nM, respectively. Neither LOS (1 μM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers markedly blunted NO release in response to ANG II (10 nM): 77±6% inhibition with LOS (n = 8) and 63±9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries, and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent NO release. Received: 24 September 1997 / Accepted: 20 October 1997     

Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

PURPOSE: Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing hormone and testosterone values are normally low. MATERIALS AND METHODS: We measured the number of spermatogonia per tubule at orchiopexy in 72 consecutive boys with cryptorchidism who underwent simultaneous testicular biopsy. In 19 patients gonadotropin releasing hormone was unsuccessful, while 8 received HCG and 45 underwent orchiopexy without hormonal therapy. Groups were otherwise equal. RESULTS: Patients who underwent surgery only had a higher number of spermatogonia per tubule than those in whom hormonal treatment was unsuccessful (p<0.05). Spermatogonia per tubule values were normal only after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally. CONCLUSIONS: In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.     

Lessons from joint development for cartilage repair in the clinic

More than 250 years ago, William Hunter stated that when cartilage is destroyed it never recovers. In the last 20 years, the understanding of the mechanisms that lead to joint formation and the knowledge that some of these mechanisms are reactivated in the homeostatic responses of cartilage to injury has offered an unprecedented therapeutic opportunity to achieve cartilage regeneration. Very large investments in ambitious clinical trials are finally revealing that, although we do not have perfect medicines yet, disease modification is a feasible possibility for human osteoarthritis.     

Should measurement of maximum urinary flow rate and residual urine volume be a part of a "minimal care" assessment programme in female incontinence?

OBJECTIVE: The aim of this study was to evaluate the value of routine measurements of urinary flow rate and residual urine volume as a part of a "minimal care" assessment programme for women with urinary incontinence in detecting clinical significant bladder emptying problems. MATERIAL AND METHODS: Four hundred and eight women were examined and treated in an open-access, interdisciplinary incontinence clinic. A standardized programme for investigation and primarily non-surgical treatment of incontinence was applied. RESULTS: Of the 408 women 43% reported subjectively incomplete bladder emptying. Twenty-six per cent had a maximum flow rate less than 15 ml/s, but only 4% at a voided volume > or =200 ml. Residual urine more than 149 ml was found in 6%. Two women had chronic retention with overflow incontinence. Both had typical symptoms with continuous leakage, stranguria and chronic cystitis. Another woman had an urethral stricture with massive bladder emptying symptoms. In the remaining 172 women with symptoms suggesting bladder emptying problems, all but 3 were managed by triple voiding and timed micturition. In these 3 patients, who also had chronic cystitis, the treatment was supplemented with clean intermittent self-catheterization. CONCLUSION: The few women (6 (1.5%)) in whom measurements of urinary flow rate and residual urine volume had a clinical therapeutic consequence, cannot justify these measurements to be routine in a "minimal care" programme for assessment of primary, uncomplicated female urinary incontinence. Thus, primary health care providers can assess women based on simple guidelines without expensive equipment for assessment of urine flow rate and residual urine.     

Intensive treatment models and coercion

Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes. Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard treatment. A higher number of bed-days in Hospital-based Rehabilitation did not influence the effect on the outcomes measured.     

Acute leukemia in adults: cost effectiveness of treatment

Costs of treating 174 adult patients with acute leukemia were compiled and analyzed over the five-year period 1974 to 1979. The average overall cost per patient was $18,760, and increased over the period of study. Increased total hospital costs were incurred by patients who achieved a favorable response to induction chemotherapy and by those with a diagnosis of acute lymphocytic leukemia (ALL). To assess the impact of successful treatment on hospital expenditures, total months of survival were compared with total hospital costs to determine cost per month of life. Using this analysis, improved survival, favorable response to chemotherapy, and a diagnosis of ALL were associated with significant decreases in cost per month of life. The long-term survivors (alive greater than or equal to 2 years from diagnosis) best demonstrated this effect, with a mean hospital cost per month of survival from diagnosis of $563, which was significantly less than $6,937 for those who achieved a partial remission, $10,703 for those with treatment failure, and $8,240 for those who were untreated. These costs linked to outcome are comparable to those reported in other disorders that require prolonged and intensive hospital care. With the progressive improvement in response rate and in percentage of long-term survivors that is being observed in adults with acute leukemia, these costs should continue to decrease.