SEARCH · PubMed Health

Results for “benign prostatic hyperplasia”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed2001

Apoptotic regression of prostatic tissue induced by short-term doxazosin treatment in benign prostatic hyperplasia.

OBJECTIVES: Benign enlargement of the prostate comprises both hypertrophy and in particular hyperplasia of prostatic stromal and glandular compartments. Alpha adrenergic blockade has been shown to be effective in the management of BPH. Recent investigations have shown that this effect may in part be due to apoptosis. METHODS: A total of 29 patients who were symptomatic due to BPH were enrolled into this prospective placebo controlled, double-blind randomized study and underwent prostatectomy at the end of the 4th week. Clinical efficacy was evaluated by a set of detailed investigations. Surgical specimens were analyzed by immunohistochemistry and tissue components of stroma, smooth muscle and glandular epithelium were calculated by a software on a computer after representative areas were scanned and captured as high resolution images. Apoptosis in each tissue specimen was analyzed by Terminal Deoxynucleotidyl Transferase End Labelling (TUNEL) method utilizing Biotin-16-dUTP. RESULTS: Both groups were similar in terms of baseline evaluation in all aspects. There was a steady decline in patients' urinary complaints as evidenced by International Prostate Symptom Score System (IPSS) in the doxazosin group compared to placebo. Uroflowmetric investigations on patients revealed that maximum flow rates in the active drug group increased throughout the study. Mean PSA levels decreased by 14% at the end of the study in the doxazosin group, while it increased by 11% in the placebo group. Average stroma to epithelial ratio in the doxazosin group was 2:1 in comparison to a value of 1:1 in the placebo group. The rate of apoptosis was 2.2% and 3.2% for the epithelial and stromal compartments, respectively, in the doxazosin group, and 1.2% and 2.7% for the placebo arm. CONCLUSIONS: These data suggest apoptosis as the possible underlying molecular mechanism partly responsible for the clinical efficacy and morphological changes induced by doxazosin treatment in BPH.

Adrenergic alpha-Antagonists↗

PubMed1992

Measuring the quality of life of patients with benign prostatic hyperplasia. Assessment of the usefulness of a new quality of life questionnaire specially adapted to benign prostatic hyperplasia patients.

A questionnaire consisting of 36 questions based on a visual analogue scale for measuring the quality of life (QOL) of benign prostatic hyperplasia (BPH) patients is presented and assessed. The sensitivity of the questionnaire is demonstrated by its ability to register a statistically significant (p less than 0.01) improvement of QOL after prostate surgery (transurethral resection of the prostate). Its reliability is shown by its ability to give reproducible results in a nonoperated BPH patient group. Patient compliance has been excellent. It is discussed to what extent questions directly concerning symptoms from prostatism should be included in QOL questionnaires for BPH patients. Nonparametric statistics are applied. It is concluded that questionnaires like this are useful tools in the assessment of BPH patients, irrespective of the treatment modality. They will probably be of particular value in studies of drug therapy of BPH, complementing methods of assessment like symptom score and urodynamic parameters.

Humans↗

PubMed2002

The pathophysiology of benign prostatic hyperplasia.

The development of human benign prostatic hyperplasia and its related signs and symptoms clearly requires a combination of testicular androgens and aging. Although the role of androgens as a causative factor for human benign prostatic hyperplasia is debated, they undoubtedly play at least a permissive role. The principle prostatic androgen is dihydrotestosterone. Two isoenzymes of 5-alpha reductase have been discovered. Type 2 is dominant in the genital issue. Testosterone is reduced by the 5-a reductase to dihydrotestosterone. Benign prostatic hyperplasia is predominantly due to stromal hyperplasia of the gland and affects more than 70% of men of 70 years or older with or without obstruction. Recent studies identified transforming growth factor-b, fibroblast growth factor and insulin-like growth factor family members as key regulators of cell proliferation and extracellular matrix turnover with interrelated activities. Furthermore, estrogens, andenergic signaling and inflammatory processes have been shown to have an impact. Without a solid understanding of the physiology and pathophysiology of benign prostatic hyperplasia it can be difficult to interpret the results of clinical trials and symptoms.

Aging↗

PubMed1999

Medical management of benign prostatic hyperplasia.

The management of benign prostatic hyperplasia has undergone a rapid evolution over the past decade from a surgical emphasis to a medical emphasis. Great strides in the development of alpha-adrenergic blockers, 5 alpha-reductase inhibitors and a variety of phytotherapeutics have fueled this evolution. This article reviews the past, present and future of the medical management of benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

PubMed2002

[Dihydrotestosterone and the role of 5 alpha-reductase inhibitors in benign prostatic hyperplasia].

The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alpha-reductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2001

[Mental disorders in patients with benign prostatic hyperplasia].

310 patients with benign prostatic hyperplasia have been studied. Their mental state being analyzed by clinical and psychometric methods using Spilberger and Hamilton scales. Neurotic disorders have been reported in all the patients: 53.8% having neurasthenic syndrome, 30% anxiety- or astheno-subdepressive syndrome, 16.2% neurotic hypochondriac symptomatology. After treatment with minor neuroleptics, antidepressants and tranquilizers, patients' psychic state improved, even when the objective urologic data remained unchanged. Treatment of mental disorders makes it possible to prepare a patient for the operation and to improve quality of life of patients with benign prostatic hyperplasia before the operation.

Aged↗

PubMed2004

Development and validation of the BSP-BPH (Bononian Satisfaction Profile--Benign Prostatic Hyperplasia) a "disease-specific" questionnaire for the evaluation of health related quality of life in patients with benign prostatic hyperplasia.

OBJECTIVES: Lower Urinary Tract Symptoms (LUTS) associated to Benign Prostatic Hyperplasia (BPH) are very common in middle aged and older men. Since BPH, and the related therapies have a significant impact on a patient's Quality of Life (QoL), the health related quality of life (HQoL) evaluation is becoming an important aspect to be considered. The present study deals with the development and validation of a BPH disease specific questionnaire (Bononian Satisfaction Profile - BSP-BPH), considering HQoL in patients seeking medical help for BPH. The innovation of this questionnaire is that the patients' scores achieved are related to their subjective satisfaction. MATERIALS AND METHODS: Questionnaire development: On the base of our previous experience with BSP-PC (a disease specific questionnaire assessing HQoL in prostate Cancer patients), of a careful review of other available instruments (SAT-P, SF-36, ICS-QoL, BPH-HqoL) and of three subsequent meetings with experts (10) and patients (20), we defined the ten life aspects mostly impaired by BPH. We created a first 72-item version of the BSP-BPH. Ten patients cross matched for age end education to our study population were asked to fill in the questionnaire. A 31 item questionnaire version, together with EuroQoL, an already generic validated instrument, was administered to 121 patients as well. Further meetings and statistical analysis defined the 18 items of the BSP- BPH. Questionnaire validation: the BSP-BPH was filled in by 435 patients enrolled in a campaign for detection of prostatic diseases held among the male population of Bologna. RESULTS: Questionnaire development: the participants' mean age was 63 years (N = 121); 47.1% had BPH. The 18 items were selected on the basis of the following criteria: a) r > 0.50, p < 0.05 (correlation test re-test); b) p < 0.05 (ANOVA presence vs absence of BPH); c) r > 0.50, p < 0.05 (correlation with EuroQol). Questionnaire validation: the participants' mean age was 63 years (N = 436). 16 patients with a history of neoplasia were excluded from our study. 21 were missing data. 45% of the sample had BPH. Principal component analysis identified 5 components: 1) satisfaction about sexual functionality (Cronbach alpha = 0.94); 2) satisfaction about social functionality (alpha = 0.80); 3) satisfaction about cognitive/emotional functionality (alpha = 0.82); 4) satisfaction about urinary functionality (alpha = 0.87); 5) satisfaction about physical functionality (alpha = 0.66); total Cronbach alpha was 0.88. CONCLUSIONS: The 18 items version of BSP-BPH questionnaire can be used as an instrument for HQoL evaluation in patients with BPH focusing on patients' subjective satisfaction. At the moment only the Italian version is available.

Humans↗

PubMed1987

Comparative study of plasma steroid and steroid glucuronide levels in normal men and in men with benign prostatic hyperplasia.

Plasma steroids were analyzed in 16 normal men and in 10 men with prostatic benign hyperplasia (BPH). The steroids measured by radioimmunoassay include pregnenolone, 17-OH-pregnenolone, dehydroepiandrosterone, androst-5-ene-3 beta, 17 beta-diol, testosterone, dihydrotestosterone, androstane-3 alpha, 17 beta-diol, androstane-3 beta, 17 beta-diol, estrone, and estradiol as well as their glucuronide derivatives. In addition, cortisol and the sulphoconjugated form of dehydroepiandrosterone were determined. Whereas the levels of pregnenolone, pregnenolone glucuronide and 17-OH-pregnenolone glucuronide are not different in the two groups, the levels of 17-OH-pregnenolone in the BPH group (0.87 +/- 0.07 ng/ml) exceed by two-fold (p less than 0.01) those observed in normal men. Plasma dehydroepiandrosterone and androst-5-ene-3 beta, 17 beta-diol concentrations are markedly elevated in the BPH group (1.49 +/- 0.23 and 0.55 +/- 0.08 ng/ml vs the control groups 0.43 +/- 0.11 and 0.31 +/- 0.05 ng/ml, respectively). Since the plasma cortisol and pregnenolone levels are comparable in these two groups, our data suggest that the elevation of plasma 17-OH-pregnenolone, dehydroepiandrosterone, and androst-5-ene-3 beta, 17 beta-diol reflects an increase of adrenal 17-hydroxylase activity in patients with BPH. A slight increase of the plasma dihydrotestosterone and androsterone glucuronide concentration is also observed in men with BPH, indicating an increase of 5 alpha-reduced androgen formation. We have also observed, in the BPH group, a 50% decrease (p less than 0.01) of plasma glucuronidated androst-5-ene-3 beta, 17 beta-diol, estrone, and estradiol levels, suggesting that the transformation of unconjugated estrogenic steroids into glucuronide derivative is inhibited in BPH patients. In summary, our data indicate that adrenal C-19 steroids might be involved in the process of BPH. Furthermore, whereas the estrogen glucuronide formation is diminished in men with BPH, the prostatic androgen metabolism as reflected by plasma dihydrotestosterone and androsterone glucuronide concentrations seems to be increased.

Aged↗

PubMed2004

[Further studies on the relationship between benign prostatic hyperplasia and prostatitis].

Benign prostatic hyperplasia(BPH) and prostatitis are two common diseases in aging men. In recent years, the study of correlation between these two diseases has been paid more and more attention to. Some researchers presumed that inflammation is one of the most important causations of BPH, however, it is not profound enough on this etiologic hypothesis at present. The writer, on the base of his clinical experiences, dissertated the etiology of BPH, the pathologic figures of coexistence of BPH and prostatitis, and the presumption of inflammation promoting BPH on the molecular biology level. We hope our colleagues pay attention to this problem, and do more study on it.

Humans↗

PubMed1995

[Treatment of prostatic benign hyperplasia with endoscopically controlled laser fiber].

Between October 1992 and February 1993, 12 patients with benign prostate hyperplasia (BPH) were treated with Neodymium-YAG laser through an endoscopically-guided right angle fibre, and follow-up is now over 1 year. Follow-up consisted in the symptomatic assessment using I-PSS questionnaires, vesicoprostate ultrasound with flowmetry and residue measurement and urethrocystometry at least every 3 months. Mean time for suprapubic catheter withdrawal was 23.4 days (range 9-34), and one patient did not resumed micturition spontaneously. Symptomatology improved after the first month. remaining stable after 6 months, with a mean score decrease at one year of 11,2 (p < 0,001). All flowmetry parameters improved although only peak and mid-stream flow showed statistical differences, peak flow increasing at one year by an average of 5,9 ml/sec (P < 0,001). In 4 of the 12 patients surgery was performed; 1 underwent early surgery due to absence of spontaneous micturition and was excluded from the results assessment, and 3 due to persistence of symptomatology at 16, 18 and 21 months post-laser. In spite of the advantages presented by the laser when compared to conventional surgical approaches, such as short time application, absence of haemorrhage and likely used in an ambulatory setting, the major initial irritative symptomatology and the need for a suprapubic catheter during at least three weeks, are in general poorly tolerated and limit its use. The apparent improvement in symptomatology after one month is not accompanied by objective changes in flowmetry, since in our series only 1 patient presented Qmax greater than 15 ml/sec with no residues. Therefore, we consider that treatment with endoscopically-guided laser fibre in BPH has, with the technology currently available. a very limited use.

Aged↗

PubMed2003

Effects of tomato sauce consumption on apoptotic cell death in prostate benign hyperplasia and carcinoma.

Population studies have suggested that lycopene, which is mostly found in tomato and tomato products, may reduce the risk of prostate cancer. We previously found that tomato sauce consumption prior to prostatectomy for prostate cancer decreased serum prostate specific antigen, decreased oxidative DNA damage, and increased lycopene concentrations in prostate tissue (Chen et al., 2001). Here, we extended those investigations to determine whether apoptotic cell death and associated Bcl-2 and Bax proteins were modulated by tomato sauce intervention. Thirty-two patients diagnosed by biopsy with prostate carcinoma were given tomato sauce pasta entrees (30 mg lycopene/day) for 3 wk before prostatectomy. Thirty-four patients with prostate cancer who did not consume tomato sauce and underwent prostatectomy served as controls. When tumor areas with the most apoptotic cells were compared in the biopsy (before) and resected prostate tissue (after), tomato sauce consumption increased apoptotic cells in benign prostate hyperplasia (BPH) from 0.66 +/- 0.10% to 1.38 +/- 0.31% (P = 0.013) and in carcinomas from 0.84 +/- 0.13% to 2.76 +/- 0.58% (P = 0.0003). When comparable morphological areas were counted, apoptotic cell death in carcinomas increased significantly with treatment, from 0.84 +/- 0.13% to 1.17 +/- 0.19% (P = 0.028), and apoptotic cell death in BPH showed a tendency toward an increase from 0.66 +/- 0.10% to 1.20 +/- 0.32% (P = 0.20). When the values of apoptotic cells in BPH and carcinomas of patients who consume tomato sauce were compared with corresponding control lesions of the patients who did not consume tomato sauce in resected prostate tissue, the differences of values were not significant [BPH 1.38 +/- 0.31% vs. 1.14 +/- 0.32% (P = 0.97); carcinomas 2.76 +/- 0.58% vs. 1.91 +/- 0.32% (P = 0.24)]. Tomato sauce consumption did not affect Bcl-2 expression but decreased Bax expression in carcinomas. These data provide the first in vivo evidence that tomato sauce consumption may suppress the progression of the disease in a subset of patients with prostate cancer by increasing apoptotic cell death. However, because of the relatively small number of control and tomato sauce-supplemented patients and the variability in the values of apoptotic cells in BPH and carcinomas, a much larger number of patients needs to be examined to support the data generated in this study.

Adenocarcinoma↗

PubMed1998

Management of benign prostatic hyperplasia in Scandinavia. A hospital questionnaire on pretreatment evaluation and treatment. The Scandinavian Urologic Association Subcommittee on Benign Prostatic Hyperplasia.

In order to describe the present status in Scandinavia of evaluation and treatment of patients presenting with symptomatic benign prostatic hyperplasia (BPH), a questionnaire was mailed to 261 relevant hospitals. In total 76% of the departments answered. Several differences between hospital types in each country were revealed, as well as differences between countries. Generally, symptom scores and urodynamics were used more often in university hospitals as compared to other types of hospitals. Symptom scores were most popular in Denmark and Sweden, while uroflowmetry generally was employed in Denmark and Finland, but less frequently in Sweden and Norway. The highest frequency of prostatic surgery was noted in Denmark. Watchful waiting accounted for the handling of 30% of the BPH patients in Finland and Sweden, in contrast to only 15% in Denmark.

Denmark↗

PubMed2003

New innovative therapies for benign prostatic hyperplasia: any advance?

PURPOSE OF REVIEW: Benign prostatic hyperplasia is the most common human neoplasm and it is the most frequent tumour requiring surgical treatment in men. Not surprisingly, interest centres on either understanding of prostatic growth during ageing or on various medical or interventional treatments. RECENT FINDINGS: Recent publications describe the interaction of various 5alpha-reductase inhibitors on the two 5alpha-reductase isoforms type 1 and 2, giving a potential new insight into the pathogenesis of benign prostatic hyperplasia. Likewise, chronic inflammation increases growth patterns of fibromuscular tissue in benign prostatic hyperplasia similar to wound healing, and a paracrine loop for chronic inflammation with overexpression of interleukin could be identified. This could be of particular importance in the further understanding of prostatic enlargement. Herbal drug treatment for lower urinary tract symptoms seems to be more effective than previously thought. According to recent publications the effectiveness is well beyond placebo effects. Likewise, alpha-blockers play an important role in treatment of lower urinary tract symptoms with alpha-1 adrenoreceptor antagonists preventing cell proliferation and apoptotic imbalances in prostatic tissue. The effect of alpha-blockers, however, may be limited by severe bladder outlet obstruction with patients at increased risk of treatment failure. Laser prostatectomy and microwave thermotherapy are under consideration as alternative treatments of benign prostatic hyperplasia. The efficacy of urodynamically proven de-obstruction as compared with transurethral resection of the prostate needs to be evaluated. Newer alternative treatments like ethanol installation or bipolar plasma kinetic vaporization have been described, but long-term results and larger patients cohort are still lacking. SUMMARY: New insights into prostatic growth and pathogenesis of benign prostatic hyperplasia are presented. Medical treatment and interventional therapies are evaluated for their safety and efficacy. Only a few new therapeutical options, however, have been published during this review period.

Adrenergic alpha-Antagonists↗

PubMed1996

[Treatment of prostate benign hyperplasia (BPH) with visually controlled laser, assessment at 2 years, and anatomopathologic findings].

The endoscopically-guided lateral discharge laser (VLAP) has been considered an alternative in the management of benign prostate hyperplasia (BPH). The purpose of this paper is to describe the technique, results obtained in 20 treated patients, and pathoanatomical findings in those later treated with prostate transurethral resection. Four patients were carriers of an indwelling catheter, while IPSS/QL mean values in the other 16 patients were 23/4. Mean maximum flow was 7.01 mL/s. Assessment after one and two years shows a fall of mean IPSS/QL to 5/1 and mean maximum flow to 15.2 mL/s and 21 mL/s, respectively, but the difference is not significant. This paper also describes the morbidity affecting 65% patients, which is comparable to the retreatment rate (15%) obtained in other series published. The results are similar to those described in the literature although, in our view, the high rate of complications undermines this choice as an alternative in BPH management.

Aged↗

PubMed2000

Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia.

OBJECTIVE: The development of the human benign prostatic hyperplasia clearly requires a combination of testicular androgens and aging. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly have at least a permissive role. The principal prostatic androgen is dihydrotestosterone (DHT). Although not elevated in human benign prostatic hyperplasia, DHT levels in the prostate remain at a normal level with aging, despite a decrease in the plasma testosterone. RESULTS: DHT is generated by reduction of testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues of the body where 5alpha-reductase is expressed and is the dominant form in sebaceous glands. Type2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used for the treatment of benign prostatic hyperplasia and male-pattern baldness. At doses used clinically, its major effect is through suppression of type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. Suppression of both 5alpha-reductase isoenzymes with GI198745 result in greater and more consistent suppression of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. Two large international multicenter, phase III trials have been published documenting the safety and efficacy of finasteride in the treatment of human benign prostatic hyperplasia. Combining these two studies, randomized, controlled data are available for 12 months. Noncontrolled extension of these data from a subset of patients, who elected to continue drug treatment for 3, 4 or 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints such as acute urinary retention or surgery. According to the meta-analysis of six randomised clinical trial with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating DHT to a greater extent than finasteride and show advantages in the treatment of human benign prostatic hyperplasia and other disease states that depend on DHT. CONCLUSION: Clinical evaluation of potent dual 5alpha-reductase inhibitors may help define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2005

Fact or fiction: what do the benign prostatic hyperplasia data tell us?

Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in men. Our understanding of this condition has improved greatly over the years and recent advances have changed our approach to management. At the end of the 19th century, prostatic enlargement was treated effectively by bilateral orchidectomy. Unsurprisingly, this treatment option never gained widespread popularity. Less than 10 years ago, surgery and watchful waiting were the only considered treatment options for BPH. We now have a number of medical therapies and minimally invasive treatment options available that can effectively manage lower urinary tract symptoms secondary to benign prostatic obstruction. However, with increased choice comes the increased need for clarity in selection and application of these various treatment options. In the current environment of evidence-based clinical practice, awareness and interpretation of data from the numerous studies is paramount. The lessons learned from these trials should be reflected clearly in our practice, with clinical management based on fact, not fiction. In this review, we critically assess the available data and understanding of the management of BPH.

Algorithms↗

PubMed1995

Benign prostatic hyperplasia specific health status measures in clinical research: how much change in the American Urological Association symptom index and the benign prostatic hyperplasia impact index is perceptible to patients?

PURPOSE: We assessed the relationship between changes in scores for the American Urological Association (AUA) symptom index and benign prostatic hyperplasia (BPH) impact index with patient global ratings of improvement in a large Veterans Affairs trial comparing different pharmacological therapies for BPH. MATERIALS AND METHODS: The primary analyses compared absolute score changes from baseline with global ratings of improvement at 13 weeks for 1,218 men. RESULTS: Subjects who rated themselves as being slightly improved had a mean decrease in AUA symptom index and BPH impact index scores of 3.1 and 0.4 points, respectively. However, the baseline scores strongly influenced this relationship. CONCLUSIONS: These data provide guidance for investigators using the AUA symptom index and BPH impact index as outcome measures.

Health Status↗

PubMed1977

Rectal invasion by benign prostatic hyperplasia.

Rectal invasion by benign prostatic hyperplasia occurred subsequent to an open transrectal biopsy of the prostate gland. Frequent transrectal resections of the prostate controlled this unusual lesion initially. However, massive intrarectal regrowth of this clinically malignant but histologically proved benign prostatic enlargement required eventual pelvic exenteration.

Humans↗