Is there a scientific basis for the therapeutic effects of serenoa repens in benign prostatic hyperplasia? Mechanisms of action.

PURPOSE: The huge resurgence of interest in herbal remedies has spawned a global industry that now competes with conventional drugs as adjuncts and/or alternatives for various conditions. The medical treatment of benign prostatic hyperplasia (BPH) is no exception. Along with alpha-blockers and 5alpha-reductase inhibitors the extract of the American dwarf palm, Serenoa repens, is unquestionably the most widely used. Together with Pygeum africanum, an extract from the bark of the African plum tree, it is licensed in Germany, France and other European countries for symptomatic BPH. This review was done to analyze the large number of in vivo and in vitro laboratory studies that have been performed with extracts of Serenoa repens to elucidate mechanism(s) of action. MATERIALS AND METHODS: A literature search (MEDLINE) revealed more than 30 publications relating to laboratory studies with extracts of Serenoa repens, addressing the question of a mechanism of action. It would appear that the n-hexane lipidosterolic extract of Serenoa repens, namely Permixon (Pierre Fabre Medicament, Boulogne, France), is a product that has uniquely been subjected to more scientific investigation than any other such preparation. RESULTS: Placebo controlled and comparative clinical studies of Permixon indicate its efficacy for BPH/lower urinary tract symptoms. Numerous mechanisms of action have been proposed, including an antiandrogenic action, an anti-inflammatory effect and an antiproliferative influence through the inhibition of growth factors. CONCLUSIONS: Set against the background of our current knowledge of the pathophysiology of the aging prostate, the results of these studies suggest a wide spectrum of activity. However, precise mechanism(s) of action remain obscure. Balance and caution are needed when extrapolating the results of in vitro laboratory studies to the complex human situation.

Subacute abdominal pain requiring hospitalization in a systemic lupus erythematosus patient: a retrospective analysis and review of the literature.

In the systemic lupus erythematosus (SLE) patient, abdominal pain is a common problem. Intraabdominal vasculitis must be excluded as the source because of its potentially high mortality rate. We retrospectively reviewed the charts of 56 SLE patients with 75 admissions for predominantly subacute abdominal pain (abdominal pain without peritoneal signs) severe enough to require hospital admission, comparing the diagnostic modalities used, ultimate diagnoses, and use of corticosteroids before admission with 56 age- and sex-matched patients without SLE admitted for abdominal pain during the same time interval. SLE patients were further subdivided by disease activity at presentation using the SELENA SLEDAI score. The in-hospital mortality for all patients in this review was 0%. There were no statistically significant differences in the use of computed tomography between SLE and control patients. Intestinal vasculitis was diagnosed in 5.4% of SLE patients compared with 0% of control patients (P = 0.0433). Only patients with SLEDAI scores >8 developed vasculitis (P < 0.001). We recommend the routine use of computed tomography to diagnose vasculitis only in patients with SLEDAI scores >8 and subacute abdominal pain. All SLE patients with SLEDAI scores <8 and subacute abdominal pain should be evaluated for a cause of abdominal pain other than vasculitis.

Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity?

UNLABELLED: PET with 18F-FDG has been shown to be useful in the detection and staging of pancreatic cancer. However, whether FDG uptake is dependent on proliferative activity is still unclear. The aim of this prospective study was to evaluate a probable correlation between FDG uptake and proliferative activity in benign and malignant pancreatic tumors. METHODS: Our series consisted of 23 patients with pancreatic cancer and 9 patients with chronic active pancreatitis (CAP). FDG PET was performed within 2 wk before surgery, and standardized uptake values (SUVs) were calculated for benign and malignant pancreatic tumors. Patients were selected when focally increased FDG uptake in previously known pancreatic tumors was present. Proliferation fraction was measured in tissue specimens using the anti-Ki-67 antibody MIB-1. A computer-assisted imaging system was used for quantification of nuclear Ki-67 immunostaining. Immunohistochemical findings were correlated to SUVS: RESULTS: Pancreatic cancer showed both intense nuclear staining of Ki-67 (39% +/- 16%) and high FDG uptake (SUV = 3.6 +/- 1.6). However, no significant correlation was found between in vivo FDG uptake and Ki-67 immunoreactivity (P = 0.65). By contrast, Ki-67 nuclear staining was significantly lower (3.8% +/- 2.7%, P < 0.05) in CAP, whereas FDG uptake was in the same range as for pancreatic cancer (SUV = 3.5 +/- 1.8). CONCLUSION: FDG uptake did not correlate with proliferative activity in pancreatic cancer. Proliferative activity was tenfold higher in malignant pancreatic tumors than in benign tumors associated with CAP, whereas FDG uptake in vivo did not differ significantly. Thus, a PET tracer indicating cellular proliferation should better differentiate between cancer and inflammatory lesions than do metabolic markers such as FDG.

Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures.

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures.

The expression and localisation of mRNAs for 5 alpha reductase Type I (5 alpha R-I) and Type II (5 alpha R-II) isoenzymes in human benign prostatic hyperplasia (BPH) were investigated by RT-PCR and by in mini hybridisation (ISH) using digoxigenin labelled riboprobes. In addition, we also examined the isoenzymes mRNA expression in primary BPH cultures of separated stroma/fibroblast and epithelial cells to determine whether primary cultures are appropriate models in which to investigate 5 alpha R activity and regulation. The results demonstrated conclusively the presence of mRNA encoding both isoenzymes in all specimens so far examined. Additionally, the presence of a functional 5 alpha R-I and -II activity in BPH was confirmed by enzyme assays. ISH studies localised the mRNA expression to both the fibroblast/stromal component as well as the epithelial cells of the hyperplastic tissue. In the glandular regions the expression for both isoenzymes was particularly strong in the basal layers of the epithelium whereas mRNA expression in the secretory cells was less pronounced. Expression of 5 alpha R-I and -II mRNAs in fibroblast was on the other hand variable with high expression in some areas and little in others. These findings were supported by our primary culture experiments which demonstrated that both the fibroblast and epithelial cells maintain a capacity to express both isoenzymes in vitro. In the case of the fibroblast, the capacity to express the isoenzymes was maintained following the sequential passaging of the cells up to passage 6, after which the cells no longer expressed either isoenzyme.

Evening primrose oil reduces urinary calcium excretion in both normal and hypercalciuric rats.

Hypercalciuria is an important risk factor in the aetiology of idiopathic urolithiasis and many treatment modalities in clinical practice are directed towards reducing urinary calcium excretion. There are no natural animal models of hypercalciuria, such as the spontaneous hypertensive rat; however, the streptozotocin-diabetic rat is accepted as a good model for studies of disordered renal function associated with diabetes mellitus. Hypercalciuria is a prominent feature of the streptozotocin-diabetic rat and the model was, therefore, used to study the influence of evening primrose oil on urinary calcium excretion. Twenty rats divided into two groups of ten rats each were maintained on either normal rat chow (group 1) or primrose oil enriched diet (group 2) for 10 weeks. At 4 weeks both groups of rats were made diabetic with streptozotocin. Urine calcium measurements were serially performed before commencement of the diet, during the pre-streptozotocin (pre-diabetic) phase and during the post streptozotocin (diabetic) phase. The urine calcium excretion was significantly less in the primrose oil fed animals during both the pre-diabetic phase and the diabetic phase compared with the rats on the normal rat chow. These results indicate that evening primrose oil, a rich source of gamma-linolenic acid, helps to reduce urine calcium excretion in normal animals as well as in the hypercalciuric streptozotocin-diabetic rat. Dietary modifications with long-chain omega-6 and omega-3 fatty acids might be a useful adjunct in the treatment of idiopathic hypercalciuric urolithiasis.

Results of treatment with pollen extract (Cernilton N) in chronic prostatitis and prostatodynia.

We report the results of a prospective study with the pollen extract, Cernilton N, in a dose of 1 tablet tid for 6 months for the treatment of chronic prostatitis syndrome in 90 patients. The factors documented before and after 3 and 6 months' treatment were digital rectal examination (DRE) of the prostate, uroflowmetry, bacterial studies, leucocyte counts in urine and measurement of complement C3/coeruloplasmin in the seminal fluid. The patients were divided into 2 groups: those without associated complicating factors (CFs) (n = 72) and those with complicating factors, i.e. urethral strictures, prostatic calculi, bladder neck sclerosis (n = 18). In the group without CFs, 56 (78%) had a favorable response; 26 (36%) were cured of their symptoms and signs and 30 (42%) improved significantly with an increase in flow rate, a reduction in leukocyturia in the post-prostate massage urine (VB3) and a decrease in complement C3/coeruloplasmin in the ejaculate. In the patients with CFs only 1 patient showed a response. Complicating factors should be considered in patients who fail to respond to treatment within 3 months. Cernilton N was well tolerated by 97% of patients.

An outbreak of waterborne cryptosporidiosis in Swindon and Oxfordshire.

An outbreak of cryptosporidiosis resulted in 516 cases in Wiltshire and Oxfordshire. The outbreak caused widespread interest and led to an official inquiry. The majority of cases were in children; 8% of cases were admitted to hospital and the median duration of illness was 3 weeks. The geographical distribution of cases matched the distribution of water supplies from three treatment works and cryptosporidium oocysts were found at these works and in the treated water. Attack rates in electoral wards supplied by the three treatment works were significantly higher than in other wards. The cause of the outbreak appeared to be the failure of normal treatment to remove oocysts. Measures at the treatment works reduced the number of oocysts detected in treated water, after which the outbreak came to an end. The conclusion of the investigations was that cryptosporidiosis is a risk of conventionally treated public water supplies.

The protective role of eicosapentaenoic acid [EPA] in the pathogenesis of nephrolithiasis.

The low incidence of atherosclerosis and other degenerative diseases including stone disease in the Greenland Eskimo has been attributed to their high consumption of oily fish with its high concentration of eicosapentaenoic acid (EPA). Man cannot synthesis EPA from the precursor essential fatty acid, linolenic acid, and can only assimilate preformed EPA present in fish and fish oil, to bring about a change in the pathway of eicosanoid metabolism from the n-6 to the n-3 series. With a westernised diet the oxygenated products of renal prostaglandin synthesis are metabolites of the n-6 series and these are known to play an important role in several pathophysiological states including stone disease. Our previous studies have shown a relationship between prostaglandin activity and urinary calcium excretion and it would seem that the initiating factor/s for stone formation trigger the mechanisms for prostaglandin synthesis resulting in the biochemical abnormalities associated with stone disease. The Eskimo may be protected from these events by possession of an eicosanoid metabolism that follows an n-3 pathway. To test this hypothesis experiments were performed using an animal model of nephrocalcinosis. The animals were divided into three groups; one group was given an intra-peritoneal injection of 10% calcium gluconate daily for 10 days to induce nephrocalcinosis; a second group was fed MaxEPA fish oil before and during the calcium gluconate injections and a third group only received an intra-peritoneal injection of N saline. A group of 12 recurrent, hypercalciuric/hyperoxaluric stone-formers were treated with fish oil for eight weeks to study the effects on solute excretion. Nephrocalcinosis, which was readily produced in the control animals, was prevented in the experimental animals by pre-treatment with fish oil and urine calcium excretion was significantly reduced. The urinary calcium and oxalate excretion in the recurrent, hypercalciuric stone-formers was significantly reduced with fish oil treatment over an eight week period. There were no untoward side-effects. These studies indicate that the incorporation of EPA in the diet as a substitute metabolic pathway could be a unique way of correcting the biochemical abnormalities of idiopathic urolithiasis.

In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth.

Nine human-derived cancer and non-cancer continuous cell lines were employed to evaluate the relative in vitro activity of the pollen extract, Cernitin T-60. Responses of the cell lines to the drug were assessed by measuring growth and cell survival as determined by cell count. The results demonstrated that of the 9 continuous cell lines tested, only those derived from the human prostate were growth inhibited by the pollen extract, whereas the non-prostate derived cells exhibited variable degrees of resistance to the T-60. The selectivity of the drug for the prostate cell lines was even more pronounced in the hormone-independent models, suggesting that there might be a place for the pollen extract in the control of abnormal growth in hormone-insensitive cells.

Treatment of outflow tract obstruction due to benign prostatic hyperplasia with the pollen extract, cernilton. A double-blind, placebo-controlled study.

Whilst prostatectomy remains the "gold standard" for the treatment of outflow tract obstruction due to benign prostatic hyperplasia, medical treatment--if only for symptomatic relief--appears to be an attractive alternative. Most of the pharmacological agents in use block the hormonal or the sympathetic neurological pathways that influence prostate growth and function. All of these drugs are known to have side effects. Sixty patients with outflow obstruction due to benign prostatic hyperplasia (BPH) were entered into a double-blind, placebo-controlled study to evaluate the effect of a 6-month course of the pollen extract, Cernilton. There was a statistically significant subjective improvement with Cernilton (69% of the patients) compared with placebo (30%). There was a significant decrease in residual urine in the patients treated with Cernilton and in the antero-posterior (A-P) diameter of the prostate on ultrasound. However, differences in respect of flow rate and voided volume were not statistically significant. It is concluded that Cernilton has a beneficial effect in BPH and may have a place in the treatment of patients with mild or moderate symptoms of outflow obstruction.

Treatment of chronic prostatitis and prostatodynia with pollen extract.

Chronic abacterial prostatitis and prostatodynia are notoriously difficult both to diagnose and to treat. These patients tend to have received several courses of antibiotics, antiinflammatory agents or adrenergic blockade and various other therapeutic manoeuvres with little success. The pollen extract, Cernilton, is reported to be effective in the treatment of this condition and we present the results of an open trial with Cernilton in a group of 15 patients with chronic prostatitis and prostatodynia. In 13 patients there was either complete and lasting relief of symptoms or a marked improvement; 2 patients failed to respond. Cernilton was found to be effective in the treatment of chronic prostatitis and prostatodynia. Its precise mode of action is not known, although experimental studies suggest that it has anti-inflammatory and anti-androgenic properties.

The use of noxythiolin (Noxyflex 'S') as an antiseptic irrigant in upper urinary tract drainage following percutaneous nephrolithotomy.

Percutaneous nephrostomy drainage for the relief of obstruction or stone removal has become a common procedure. Despite the routine use of prophylactic antibiotics, nephrostomy urine frequently becomes infected (approximately 30% of cases). Noxythiolin irrigation has been used to prevent and treat bladder infections. A double-blind, placebo controlled study was carried out in 20 patients undergoing a single-stage percutaneous nephrolithotomy to evaluate the use of noxythiolin as an upper urinary tract antiseptic. In the patients whose nephrostomy tubes were irrigated with a 2.5% solution of noxythiolin, significant bacterial infection was eliminated from the nephrostomy urine and colonisation of the catheter tip was markedly reduced. Noxythiolin also rendered pre-operative infected bladder urine sterile. There were no untoward local or systemic sequelae in either group of patients. This study indicates that irrigation of the upper urinary tract with noxythiolin solution is safe and may be a useful adjunct to reduce the risk of sepsis in patients undergoing percutaneous drainage procedures.

Disseminated intravascular coagulation with Fusobacterium necrophorum septicaemia.

A 23 year old woman died within six hours of admission from acute disseminated intravascular coagulation. Fusobacterium necrophorum, a Gram negative anaerobic organism, was isolated as a single pathogen from the blood cultures. This association has not previously been reported.

The treatment of metastatic prostatic cancer with the slow release LH-RH analogue Zoladex ICI 118630.

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Ultrasound assessment of residual urine. A quantitative method.

A method of measuring residual urine volume using ultrasound is described. The volume is computed from serial parallel sections of the bladder. This method is found to be significantly more accurate than previously reported techniques and is quick and easy to perform.

Treatment of patients with advanced cancer of the prostate using a slow-release (depot) formulation of the LHRH agonist ICI 118630 (Zoladex).

Twenty two patients with advanced carcinoma of the prostate have been treated for up to 3 months with the slow-release (depot) formulation of the luteinizing hormone-releasing hormone (LHRH) agonist ICI 118630. Patients were randomized to receive one of three different doses of ICI 118630 of 0.9, 1.8 or 3.6 mg. The depot preparation was injected subcutaneously every 4 weeks. At the highest dose, the concentration of testosterone in serum was significantly reduced to castrate values after 2-3 weeks of therapy. The smaller doses of ICI 118630 (1.8 or 0.9 mg every 4 weeks) similarly reduced serum testosterone concentrations although, at the lowest dose, testosterone values were not suppressed in all patients during the first month. Hormonal changes were accompanied by subjective clinical improvement in symptomatic patients and there were no significant side effects. The data clearly demonstrate the considerable therapeutic potential of ICI 118630 in the depot formulation for the treatment of advanced carcinoma of the prostate.

Ultrasonic appearances associated with prostatic inflammation: a preliminary study.

Per-rectal ultrasonography was performed on 40 patients in whom a diagnosis of prostatitis had been made on the basis of symptoms and signs of prostatic inflammation confirmed by bacteriology, microscopy or pH changes of expressed prostatic secretion. Certain ultrasonic features were present in all patients to a variable degree. A change in volume and weight of the prostate could be an indicator of treatment response.