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Alpha 1a-adrenoceptor polymorphism: pharmacological
characterization and association with benign prostatic
hypertrophy.
Shibata K; Hirasawa A; Moriyama N; Kawabe K; Ogawa S;
Tsujimoto G
Department of Molecular, Cell Pharmacology, National
Children's Medical Research Center, Tokyo, Japan.
Br J Pharmacol (England) Jul 1996, 118 (6)
p1403-8
1. Two restriction fragment length polymorphisms of the
human alpha 1a-adrenoceptor gene digested with PstI
restriction enzyme exist; the nucleotide change causes the
substitution of C residue for T at nucleotide 1441, thereby
Arg492 to Cys492 transition, which might confer an additional
putative palmitoylation site in the carboxy-terminal segment
of the alpha 1a-adrenoceptor. In the present study, we
compared their pharmacological properties and examined whether
this alpha 1a-adrenoceptor polymorphism is associated with
benign prostatic hypertrophy (BPH).
2. The frequency of alpha 1a-adrenoceptor polymorphism was
not differently distributed between patients with benign
prostatic hypertrophy (BPH) and normal subjects in Japan;
thus, the relative frequencies of the C and T alleles were
0.90 : 0.10 in normal male subjects (n = 45) and 0.87 : 0.13
in BPH patients (n = 222), respectively. However, the
frequency distribution of this polymorphism was significantly
different between the Japanese and U.S. populations; thus, C
and T alleles were 0.34 and 0.66 in U.S. populations.
3. Utilizing Chinese hamster ovary (CHO) cells stably
expressing the two polymorphic alpha 1a-adrenoceptors (Arg492
and Cys492), we compared their binding affinity and signal
transduction. Radioligand binding studies with
2-[beta-(4-hydroxy-3[125I]-iodophenyl)
ethylamino-methyl]tetralone ([125I]- HEAT) showed no marked
difference in the antagonist or agonist binding affinities
between the two receptors. Also, both receptors were found to
be coupled to the calcium signaling, and the
concentration-cytosolic Ca2+ concentrations ([Ca2+]i) response
relationships for noradrenaline were similar for the two
polymorphic receptors. Furthermore, the receptor-mediated
[Ca2+]i response was markedly desensitized after a 2 h
exposure of phenylephrine (10 microM), and the extent of the
desensitization was not significantly different between the
two receptors.
4. In summary, the results showed that the two alpha
1a-adrenoceptors generated by genetic polymorphism have
similar pharmacological characteristics, and the
receptor-mediated [Ca2+]i response can be desensitized in a
similar manner. The study did not provide any evidence to
support the hypothesis that alpha 1a-adrenoceptor gene
polymorphism is associated with BPH.
[Double-blind evaluation of mepartricin 150.000 U
(40 mg) compared with placebo in benign prostatic
hypertrophy]
Prezioso D; Mirone V; Fabrizio F; Lotti T
Cattedra di Urologia, II Facolta di Medicina, Universita
degli Studi, Napoli.
Minerva Urol Nefrol (Italy) Dec 1996, 48 (4)
p207-11
The therapeutic efficacy and tolerance of a new 150,000 U
(40 mg) formulation of mepartricin (to be administered
once-a-day in the evening) were evaluated during a
double-blind study against placebo in 2 groups of
uncomplicated BPH patients treated for 60 days. The data
obtained disclosed a positive pharmaco-therapeutic effect of
this new formulation coupled with excellent local and systemic
tolerance. At the end of trial the various objective and
subjective parameters considered showed marked improvement in
the group treated with mepartricin, with statistically
significant differences from the placebo-treated group. The
treatment efficacy was judged positive in 74-78% of cases by
patients and physicians in the mepartricin group and in 36.4%
of cases in the placebo group.
[Alternative treatment of benign prostatic
hypertrophy]
Fiorelli C; Menghetti I; Razmjouei K; Macchiarella A; Celso
M
Clinica Urologica I, Universita degli Studi, Firenze.
Minerva Urol Nefrol (Italy) Dec 1996, 48 (4)
p177-82
In our study we propose to find an alternative to surgery
management of IPB usable in DH regime with current
instrumentation or with new technology from physics. We
retrospectively reviewed techniques commonly mentioned in the
literature to value benefits about cost, comfort, outcomes,
and, at the same time, we stress disadvantages regarding each
of these. TUI is economical, can be done in a few minutes,
involves minimum bleeding, but can't be utilized in III lobe
prostate and it doesn't provide material for histological
tests. TUBT, feasible with light patient sedation, provides
not satisfying results. Hyperthermia is necessary in selected
cases. TULIP must be effected in anesthesia, needs complicated
and expensive instrumentation, and it isn't practicable in III
lobe prostate. Urethral stent application is expensive and not
satisfactory in large size and III lobe prostate. The outcomes
we obtained with TUI are similar to TUR; TUBT obtains good
symptomatological results only in 20% of cases at 12 months.
Hyperthermia and TULIP obtain an improvement in urinary flow
rate from 20 to 60% and 50% respectively. Stent application
provides good results. We think that the most modern,
effective and economical alternative to the surgery of
prostate adenoma is endoscopic surgery in TUI model. (19
Refs.)
Transition zone ratio and prostate-specific antigen
density: the index of response of benign prostatic hypertrophy
to an alpha blocker.
Kurita Y; Ushiyama T; Suzuki K; Fujita K; Kawabe K
Department of Urology, Hamamatsu University School of
Medicine, Japan.
Int J Urol (Japan) Sep 1996, 3 (5) p361-6
BACKGROUND: The aim of the present study was to determine
whether the indices of transrectal ultrasonography (TRUS) are
related to the clinical response to tamsulosin, a long-acting
selective alpha 1-blocker.
METHODS: Sixty patients with symptomatic benign prostatic
hypertrophy (BPH) were treated with tamsulosin hydrochloride
(0.2 mg/day) for 2 months. The findings on TRUS and
uroflowmetry and the AUA symptom score before treatment were
compared with those obtained at the end of the 2 month
treatment period. For the indices of TRUS, transition zone
(TZ) volume, transition zone ratio (TZ ratio = TZ volume/total
prostate volume), total prostate volume, and prostate specific
antigen density (PSAD) were calculated.
RESULTS: There was a significant correlation between the
pretreatment TZ ratio and the residual urine volume (r =
0.421, P = 0.0005). Patients with a lower TZ ratio and/or PSAD
responded well to the treatment. The correlation between the
PSAD value and the percent change in peak urinary flow rate
was statistically significant (r = -0.432, P = 0.0009).
CONCLUSION: TRUS provides simple parameters of PSAD that
can be used to predict the response of patients to tamsulosin
hydrochloride.
[A case of prostate cancer diagnosed one and half
year after retropubic prostatectomy for benign prostatic
hypertrophy]
Kato Y; Nakata S; Sato J; Mayuzumi T; Shimizu T
Department of Urology, Gunma Cancer Center.
Hinyokika Kiyo (Japan) Nov 1996, 42 (11) p907-9
A 77-year-old male patient underwent retropubic
prostatectomy for benign prostatic hypertrophy. Fourteen
months after operation, a hard nodule was palpated on the left
lobe on digital examination. Transrectal needle biopsy was
performed, and the pathological diagnosis was poorly
differentiated adenocarcinoma of the prostate. It was one and
half year after prostatectomy that we diagnosed prostate
cancer (stage D2). (8 Refs.)
The use of alpha-adrenoceptor antagonists in the
pharmacological management of benign prostatic hypertrophy: an
overview.
Hieble JP; Ruffolo RR Jr
SmithKline Beecham Pharmaceuticals, King of Prussia, PA
19406-0939, USA.
Pharmacol Res (England) Mar 1996, 33 (3) p145-60
Benign prostatic hypertrophy (BPH) produces symptomatic
urethral obstruction in a significant percentage of older men.
Since the incidence of BPH is age related, the clinical and
economic impact of this disease will continue to progress as
average lifespan increases. BPH is associated with growth of
both glandular and stromal elements of the prostate gland.
Glandular hyperplasia can be partially reversed by withdrawal
of androgenic tone with androgen receptor antagonists or
steroid-5-alpha-reductase inhibitors. However, the reduction
in prostatic size produced by these agents has little effect
on the dynamic tone induced by nerve mediated contraction of
stromal smooth muscle. This tone is mediated by activation of
alpha-adrenoceptors. Therefore the alpha-adrenoceptor
antagonists represent a useful pharmacological approach to the
treatment of BPH. Studies in isolated strips of human prostate
show that either exogenous alpha-adrenoceptor agonists or
electrical field stimulation will induce contraction. Studies
with selective antagonists such as prazosin show that this
response is mediated by the alpha 1-adrenoceptor, even though
radioligand binding studies show the presence of alpha 1 and
alpha 2 adrenoceptor subtypes in approximately equal density.
Following the cloning of multiple alpha 1-adrenoceptors, the
contractile response in human prostate has been assigned to
the alpha 1A adrenoceptor. However, recent data would suggest
a functional role for another subtype, which has not yet been
cloned, and designated as alpha 1L based on a relatively low
affinity for prazosin. Clinical trials have shown efficacy of
a variety of alpha-adrenoceptor antagonists in BPH, including
non-selective agents such as phenoxybenzamine, as well as a
variety of selective alpha 1-adrenoceptor antagonists, most
structurally related to prazosin. The agents most commonly
employed at the present time include the prazosin analogs
terazosin, doxazosin and alfuzosin, as well as the
structurally unrelated indoramin and tamsulosin. The design of
new alpha 1-antagonists for BPH has concentrated on agents
producing preferential blockage of urogenital vis-a-vis
vascular alpha 1-adrenoceptors, based either on selectivity
for the alpha 1A-adrenoceptor subtype or on functional
uroselectivity in animal models. While these newer agents
offer the prospect of reducing the incidence of the
cardiovascular side effects associated with current therapy
their superiority over nonselective alpha 1-adrenoceptor
antagonists remains to be demonstrated in the clinical
setting. (158 Refs.)
Clinical application of basic arginine amidase in
human male urine.
Matsuda Y; Miyashita A; Fujimoto Y; Umeda T; Akihama S
Department of Biochemistry, Meiji College of Pharmacy, Tokyo,
Japan.
Biol Pharm Bull (Japan) Aug 1996, 19 (8) p1083-5
Basic human urinary arginine amidase (or esterase, called
BHUAE) which is only found in male urine, was measured from
normal volunteers between the age of 4 and 70 years using
D-valyl-L-leucyl-L-arginine-p-nitroanilide as a substrate.
BHUAE increases during early adolescence, between 8 to 17
years of age. Then, BHUAE decreases in the twenties and takes
a certain range of value in the mature age group, between the
late thirties and fifties. In patients with prostate cancer, a
significant increase in BHUAE was demonstrated in comparison
with the healthy male group (control) over 55 years old. On
the other hand, patients with benign prostatic hypertrophy
showed no significant elevation of this enzyme activity. It
would appear that the measurement of BHUAE in urine can be
used as a marker of prostate cancer in an advanced age
group.
Free to total prostate-specific antigen (PSA) ratio
is superior to total-PSA in differentiating benign prostate
hypertrophy from prostate cancer.
Van Cangh PJ; De Nayer P; Sauvage P; Tombal B; Elsen M; Lorge
F; Opsomer R; Wese FX
Department of Urology, Saint Luc University Hospital,
Brussels, Belgium.
Prostate Suppl (United States) 1996, 7 p30-4
BACKGROUND: Serum prostate-specific antigen (PSA) exists in
different molecular forms, and their respective concentration
has been proposed as a useful tool to improve discrimination
between benign prostatic hypertrophy (BPH) and prostate cancer
(PC).
METHODS: The relevance of the free to total PSA ratio was
prospectively studied in a selected urology clinic population
of 420 patients. Total serum PSA ranged from 2.1 to 30 ng/ml;
154 had PC and 266 had BPH.
RESULTS: Receiver operating characteristic (ROC) curves
were constructed for the total population (total-PSA range
from 2.1 to 30 ng/ml) and for the diagnostic gray zone of
2.1-10 ng/ml. For the two groups, the free to total PSA ratio
had a higher specificity than total-PSA for all sensitivity
levels. Cut-off values were found to, vary with prostate
weight.
CONCLUSIONS: Although free to total PSA ratio demonstrated
better performances than total-PSA, its use in screening
appears problematic, due to the low prevalence of prostate
cancer.
Clinical study on estramustine binding protein
(EMBP) in human prostate.
Shiina H; Igawa M; Ishibe T
Department of Urology, Shimane Medical University, Izumo,
Japan.
Prostate (United States) Sep 1996, 29 (3)
p169-76
To elucidate the characteristics of estramustine binding
protein (EMBP) in human prostate, tissue EMBP concentration
was examined in 42 benign prostatic hypertrophy (BPH), 34
untreated prostatic carcinoma (PC), 8 hormone refractory PC
(hr-PC), as well as 13 control prostate human tissue samples
by RIA using rat-EMBP antibody, and the concentration thus
obtained was compared with dihydrotestosterone (DHT),
prostatic acid phosphatase (PAP), prostate-specific antigen
(PSA), and zinc, indices exhibiting androgen dependency in the
prostate. EMBP concentration correlated significantly with DHT
and PSA levels in the control prostate and BPH, but not in
untreated PC. In BPH, EMBP concentration increased
significantly after administration of fluoxymesterone (4
mg/day for 2 weeks), whereas it decreased significantly after
estramustine phosphate (280 mg/day for 2 weeks). The EMBP/DHT
ratio in moderately and poorly differentiated, and the hr-PC
was significantly higher than in controls, BPH, and
well-differentiated PC. In addition, untreated PC with an
EMBP/DHT ratio of more than 40 showed significantly lower
progression-free probability as compared with PC with an
EMBP/DHT of less than 40. These results suggest that (1) EMBP
in BPH and well-differentiated PC preserves androgen
dependency, but not in moderately and poorly differentiated,
nor in hr-PCs, indicating that EMBP is a protein different
from PAP and PSA, and (2) that the tissue EMBP/DHT ratio might
be useful as a marker for predicting disease progression.
Three-year followup of patients treated with lower
energy microwave thermotherapy.
de Wildt MJ; D'Ancona FC; Hubregtse M; Carter SS; Debruyne
FM; de la Rosette JJ
Department of Urology, Nijmegen University Hospital, The
Netherlands.
J Urol (United States) Dec 1996, 156 (6)
p1959-63
PURPOSE: A retrospective study was done to investigate the
long-term outcome of patients treated with lower energy
transurethral microwave thermotherapy.
MATERIALS AND METHODS: A total of 305 patients with lower
urinary tract symptoms and benign prostatic hypertrophy
underwent transurethral microwave thermotherapy according to a
similar protocol at 2 centers.
RESULTS: After 3 years of followup 133 patients who had
undergone transurethral microwave thermotherapy alone were
available for study. During this observation period
significant symptomatic improvement from baseline and an
improved maximum flow rate of 2.6 ml. per second were noted.
Of the patients 125 underwent invasive or medical
treatment.
CONCLUSIONS: After 3 years of followup lower energy
transurethral microwave thermotherapy showed significant and
durable improvements in baseline parameters in 52% of the
patients.
Detection of Chlamydia trachomatis in the prostate
by in-situhybridization and by transmission electron
microscopy.
Corradi G; Bucsek M; Panovics J; Verebelyi A; Kardos M; Kadar
A; Frang D
Semmelweis University of Medicine, Budapest, Hungary.
Int J Androl (England) Apr 1996, 19 (2) p109-12
Chlamydia trachomatis infection has been investigated in
the prostate gland using in-situ DNA hybridization and
transmission electron microscopy. Sixty-four samples of tissue
removed by trans-urethral resection or by open surgery from
men with benign prostatic hypertrophy (BPH), were examined
histologically and 20 of the cases were found to be positive
for mononuclear cell infiltration. Some samples were then
investigated using in-situ hybridization and transmission
electron microscopy. Out of 20 tissue samples with mononuclear
cell infiltration, nine were found to be positive for C.
trachomatis infection.
Breast and prostate cancer in the relatives of men
with prostate cancer.
McCahy PJ; Harris CA; Neal DE
Department of Surgery, University of Newcastle upon Tyne,
UK.
Br J Urol (England) Oct 1996, 78 (4) p552-6
OBJECTIVE: To assess the risk of breast, ovarian and
prostate cancer in the families of men with prostate
cancer.
PATIENTS AND METHODS: A case-control study was performed by
interviewing patients with prostate cancer and obtaining
detailed information on family histories of cancer. Controls
were hospital-based patients, of a similar age to the cases,
with bladder cancer or benign prostatic hypertrophy.
RESULTS: A total of 209 cases and 322 controls were
interviewed; of the cases, 22.5% had family members with a
history of one or more of breast, ovarian or prostate cancers,
compared with 15.2% of controls (P < 0.05). The odds ratio
(OR) of having prostate cancer when there was a positive
family history was 8.22 and the OR of a female relative of a
patient with prostate cancer having breast cancer was 1.51.
There was no apparent increased risk of ovarian or any other
cancer.
CONCLUSIONS: We confirm previous reports of an increased
incidence of prostate cancer in the families of men with
prostate cancer and report a similarly increased incidence of
breast cancer in female relatives. We suggest that detailed
family histories be taken routinely and intend to analyse
blood samples provided from this study for genetic
abnormalities.
Effect of finasteride on free and total serum
prostate-specific antigen in men with benign prostatic
hyperplasia.
Matzkin H; Barak M; Braf Z
Department of Urology, Tel-Aviv University, Israel.
Br J Urol (England) Sep 1996, 78 (3) p405-8
OBJECTIVE: To examine changes in the free-to-total (f/t)
serum prostate-specific antigen (PSA) ratio among men treated
with finasteride for benign prostatic hypertrophy.
PATIENTS AND METHODS: Blood samples were taken from 20 men
(mean age 71 years, range 61-87) before and after a minimum of
9 months of treatment with finasteride and the f/tPSA ratio
determined using the Immulite assay system.
RESULTS: Although mean total and free PSA levels decreased
significantly, the mean f/tPSA ratio increased only slightly
and not significantly; the ratios remained unchanged in men
with an initially low or high (< > 10%) ratio.
CONCLUSIONS: Concern has been expressed over the loss of
the discriminatory power of serum PSA in a patient receiving
treatment with finasteride. The f/tPSA ratio, currently used
to help differentiate benign from malignant processes in the
prostate, remains valid during treatment with finasteride; it
does not affect the f/tPSA ratio.
The safety of finasteride used in benign prostatic
hypertrophy: a non-interventional observational cohort study
in 14,772 patients.
Wilton L; Pearce G; Edet E; Freemantle S; Stephens MD; Mann
RD
Drug Safety Research Unit, Southampton, UK.
Br J Urol (England) Sep 1996, 78 (3) p379-84
OBJECTIVE: To examine the safety of finasteride as used in
general medical practice to treat benign prostatic hypertrophy
(BPH).
PATIENTS AND METHODS: Information was collected on 14,772
patients who were included in an observational cohort study
conducted using Prescription-Event Monitoring.
RESULTS: Finasteride was reported to have been effective in
60% of the patients in whom an opinion on efficacy was
recorded. Impotence or ejaculatory failure was reported in
2.1% of the patients, decreased libido in 1% and gynaecomastia
and related conditions in 0.4%. Impotence was the most
frequent reason for stopping treatment with finasteride and
was the most commonly reported adverse reaction to the drug.
Of the patients included in the elderly cohort involved in
this study, 819 (5.5%) died; none of these deaths was
attributed to finasteride.
CONCLUSION: Impotence or ejaculatory failure, decreased
libido and gynaecomastia in a small proportion of patients
were associated with the use of finasteride. The results of
this study strongly suggest that this drug is acceptably safe
when used in accordance with the current prescribing
information.
[Transurethral thermotherapy with microwaves in
patients with benign prostatic hypertrophy and urinary
retention: comparative study between high energy (25) and
standard energy (2.0)]
Mompo Sanchis JA; Paya Navarro JJ; Prosper Rovira F
Centro Medico Urotecno, Clinica Casa de Salud, Valencia,
Espana.
Arch Esp Urol (Spain) May 1996, 49 (4) p337-46
OBJECTIVES: During a 36-month period, 63 patients with
benign prostatic hypertrophy (BPH) who presented urinary
retention, were treated on an outpatient basis by
transurethral microwave thermotherapy (TUMT) with the
Prostatron device using analgosedation.
METHODS: Treatment consisted of a single one hour session
with Prostasoft 2.0 for the first group of 11 patients. The
second group of 19 patients received 2 hours Prostasoft 2.0.
The third group comprised of 33 patients were treated with
higher energy TUMT (Prostasoft 2.5/1 h 30 min). The number of
sessions (144) depended on prostate length: L < 45 mm: one
session (Prostanec catheter); L < 55 mm: two sessions
(additional black catheter session); L < 65 mm: three
sessions (additional white catheter session).
RESULTS: In the first group of patients, 54% were
catheter-free after one year (5 TURP); 84% (3 TURP) in the
second group; 96% (1 TURP) in the third group. The morbidity
was similar for all groups.
CONCLUSIONS: Only high energy TUMT (Prostasoft 2.5/1 h 30
min) appears to be a minimally reasonable alternative to
surgery in elderly patients with urinary retention secondary
to prostatism and concomitant diseases. Longer followup is
warranted to determine if the beneficial effects will
persist.
Detection of alpha 1-adrenoceptor subtypes in human
hypertrophied prostate by insituhybridization.
Moriyama N; Kurimoto S; Horie S; Nasu K; Tanaka T; Yano K;
Hirano H; Tsujimoto G; Kawabe K
Department of Urology, Faculty of Medicine, University of
Tokyo, Japan.
Histochem J (England) Apr 1996, 28 (4) p283-8
Adrenergic stimulation induces contraction of hypertrophied
prostatic tissue via the alpha 1 adrenoceptor, and the results
of pharmacological studies suggested the existence of
adrenoceptor subtypes. Recently three subtypes (alpha 1a,
alpha 1b, and alpha 1d) were cloned. Using probes for these
subtypes, we demonstrated their expression in the tissues of
ten cases of benign prostatic hypertrophy, using in situ
hybridization. To determine the ratio between these subtypes,
an RNase protection assay was also performed in three cases.
Expression of the alpha 1a and alpha 1d adrenoceptors was
diffuse in the smooth muscles of the interstitium, but was
absent in glandular epithelial cells. On the contrary, the
alpha 1b adrenoceptor was hardly detectable. The RNase
protection assay confirmed the absence of the alpha 1b
adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1.
These results supported the idea that the differences in
prostatic contractile response to several adrenergic drugs are
based on the affinities of these drugs for the different
subtypes.
Safety profile of 3 months' therapy with alfuzosin
in 13,389 patients suffering from benign prostatic
hypertrophy.
Lukacs B; Blondin P; MacCarthy C; Du Boys B; Grippon P;
Lassale C
Service Urologie, Hopital Tenon, Paris, France.
Eur Urol (Switzerland) 1996, 29 (1) p29-35
The safety profile of alfuzosin, a selective alpha
1-adrenergic antagonist, was assessed in a total of 13,389
patients (mean age 66.9 +/- 8.5 years) with symptomatic benign
prostatic hypertrophy in two open, noncontrolled, multicentre,
post-marketing surveillance studies, both conducted in France.
Alfuzosin was prescribed at the recommended dose of 2.5 mg
t.i.d., according to the current labelling recommendations,
for a 3-month period. Clinical safety was assessed using
spontaneous reporting of adverse events leading to
discontinuation of treatment. Overall, 89.7% of the patients
completed the treatment period. Drop outs were recorded in
10.3% of patients: 3.7% for intolerance; 1.5% for resolution
of urinary symptoms; 2.1% for lack of efficacy, and 3.0% for
loss to follow-up, noncompliance, and miscellaneous reasons.
Two thirds of the adverse events leading to discontinuation
were vasodilatory and occurred in 2.7% of the patients:
vertigo/dizziness (1.4%); malaise (0.6%); hypotension (0.4%),
and headache (0.4%). Other adverse events (predominantly
gastrointestinal disorders) were recorded in < 1.2% of the
patients. Three quarters of the adverse events occurred during
the first week of therapy. As expected, adverse events were
more frequent in the elderly (aged over 75 years) and in
patients taking cardiovascular drugs or with concomitant
cardiovascular disease. Overall, alfuzosin was very well
tolerated and the adverse event profile was consistent with
the cumulative experience of the drug. No unexpected or
serious adverse events considered to be related to alfuzosin
were recorded. Particular care must be taken when prescribing
for very elderly patients and/or those with concomitant
cardiovascular disease for which they are receiving
therapy.
Estramustine-binding protein in carcinoma and
benign hyperplasia of the human prostate.
Shiina H; Urakami S; Shirakawa H; Igawa M; Ishibe T; Usui
T
Department of Urology, Shimane Medical University, Izumo,
Japan.
Eur Urol (Switzerland) 1996, 29 (1) p106-10
For the purpose of elucidating whether the biological
characteristics of estramustine-binding protein (EMBP) are
different in benign prostatic hypertrophy (BPH) and prostatic
carcinoma (PC) and also to determine the clinical value of
EMBP in the tissue, the EMBP concentration in 19 patients with
BPH and 26 with untreated PC was measured by means of
radioimmunoassay (RIA) using an antibody raised against EMBP
obtained from the rat ventral prostate and compared
simultaneously with the dihydrotestosterone (DHT) level in the
same tissue. The level of serum prostate-specific antigen
(PSA) was also measured in these patients. The EMBP
concentration was significantly correlated with the tissue DHT
level in BPH and well-differentiated PC (r = 0.745, p <
0.0001), whereas it did not correlate in moderately and poorly
differentiated PC (r = -0.159, p = 0.542). By comparing
well-differentiated PC with moderately and poorly
differentiated PC, the EMBP concentration was significantly
lower in the former than in the latter two conditions (p <
0.005) in spite of the highest tissue DHT level in
well-differentiated PC. The ratio of the EMBP concentration to
the DHT level in moderately and poorly differentiated PC was
significantly higher when compared with that observed in
either BPH or well-differentiated PC (p < 0.005,
respectively). However, the level of serum PSA did not reflect
the histological differentiation of PC. These results suggest
that: (i) the correlation of the EMBP concentration to the DHT
level changed with the progression of the histological grade,
and (ii) the ratio of the EMBP concentration to the DHT level
in the tissue is clinically valuable in elucidating the
biological potential of individual tumors.
Surface-epitope masking and expression cloning
identifies the human prostate carcinoma tumor antigen gene
PCTA-1 a member of the galectin gene family.
Su ZZ; Lin J; Shen R; Fisher PE; Goldstein NI; Fisher
PB
Department of Pathology, Columbia University, College of
Physicians and Surgeons, New York, NY 10032, USA.
Proc Natl Acad Sci U S A (United States) Jul 9 1996, 93 (14)
p7252-7
The selective production of monoclonal antibodies (mAbs)
reacting with defined cell surface-expressed molecules is now
readily accomplished with an immunological subtraction
approach, surface-epitope masking (SEM). Using SEM, prostate
carcinoma (Pro 1.5) mAbs have been developed that react with
tumor-associated antigens expressed on human prostate cancer
cell lines and patient-derived carcinomas. Screening a human
LNCaP prostate cancer cDNA expression library with the Pro 1.5
mAb identifies a gene, prostate carcinoma tumor antigen-1
(PCTA-1). PCTA-1 encodes a secreted protein of approximately
35 kDa that shares approximately 40% sequence homology with
the N-amino terminal region of members of the S-type
galactose-binding lectin (galectin) gene family. Specific
galectins are found on the surface of human and marine
neoplastic cells and have been implicated in tumorigenesis and
metastasis. Primer pairs within the 3' untranslated region of
PCTA-1 and reverse transcription-PCR demonstrate selective
expression of PCTA-1 by prostate carcinomas versus normal
prostate and benign prostatic hypertrophy. These findings
document the use of the SEM procedure for generating mAbs
reacting with tumor-associated antigens expressed on human
prostate cancers. The SEM-derived mAbs have been used for
expression cloning the gene encoding this human tumor antigen.
The approaches described in this paper, SEM combined with
expression cloning, should prove of wide utility for
developing immunological reagents specific for and identifying
genes relevant to human cancer.
[The significance of free-type PSA and complex-type
PSA in patients with prostatic carcinoma--the characteristics
of ACS-PSA method compared with that of Delfia- and Eiken-PSA
method]
Arai K; Honda M; Hosoya Y; Sumi S; Umeda H; Yoshida K
Department of Urology, Dokkyo University School of Medicine,
Tochigi, Japan.
Rinsho Byori (Japan) Apr 1996, 44 (4) p345-50
We studied the clinical significance of free-type prostate
specific antigen (PSA) and bound-type PSA in serum of the
patients with prostatic carcinoma and benign prostatic
hypertrophy. The levels of PSA, gamma-seminoprotein and
prostatic acid phosphatase (PAP) in 17 healthy adult males, 20
patients with benign prostatic hypertrophy and 23 patients
with prostatic carcinoma were measured by ACS-PSA, Delfia and
Eiken-PSA method. The levels of PSA in serum from prostatic
carcinoma patients was significantly elevated as compared with
that from benign prostatic hypertrophy. Linear regression
analysis of the data showed that, although overall
correlations were well, different assays gave different PSA
concentrations. We have studied the forms of PSA in serum by
gel filtration technique and measured PSA levels in each
fractions using three methods. Moreover, the characteristics
of ACS-PSA method was compared with that of Delfia and
Eiken-PSA method. Two peaks of PSA were detected on the
elution profiles from three prostatic carcinoma patients sera.
Those were estimated complex-type PSA (90kDa) and free-type
PSA (30kDa). The complex-type PSA fractions detected by
ACS-PSA method were almost identical with that detected by
Delfia-PSA method, while free-type PSA fractions detected by
ACS-PSA method were greater quantity than those by Delfia and
Eiken method. Many factors were contributory to the difference
between the assay kits on serum complex-type PSA and free-type
PSA levels. The present results suggest that there are some
quantitative differences in the immunorecognition of
complex-type PSA and free-type PSA between the assay kits.
The Oxford Laser Prostate Trial: a double-blind
randomized controlled trial of contact vaporization of the
prostate against transurethral resection; preliminary
results.
Keoghane SR; Cranston DW; Lawrence KC; Doll HA; Fellows GJ;
Smith JC
Department of Urology, Churchill Hospital, University of
Oxford, UK.
Br J Urol (England) Mar 1996, 77 (3) p382-5
OBJECTIVE: To compare the results of contact laser
vaporization and transurethral resection of the prostate
(TURP) in a double-blind randomized controlled clinical
trial.
PATIENTS AND METHODS: The study comprised 148 patients with
clinical benign prostatic hypertrophy (BPH) who were recruited
and allocated randomly to undergo either TURP (72 patients) or
laser ablation of the prostate (76 patients). The outcome was
assessed using the American Urological Association (AUA -7)
symptom score after 1 and 3 months as the primary measure and
by urinary flow rates, haematological factors and the duration
of hospital stay and length of catheterization.
RESULTS: With 90% statistical power, the results at 3
months showed no clinical or statistical difference between
the treatments in change in AUA symptom score. A lower blood
loss, hospital stay and duration of catheterization
significantly favoured the laser treatment, although the
failure rate of trial without catheter and the rate of
re-operation were higher after laser treatment.
CONCLUSIONS: These early data are encouraging for this
technique, although the outcome after one year requires
evaluation before advocating the widespread uptake of this
method.
A case-control study of cancer of the prostate in
Somerset and east Devon.
Ewings P; Bowie C
Somerset Health Authority, Taunton, UK.
Br J Cancer (England) Aug 1996, 74 (4) p661-6
A case-control study in Somerset and east Devon was
undertaken to investigate possible risk factors for prostatic
cancer. A total of 159 cases, diagnosed at Taunton. Yeovil and
Exeter hospitals between May 1989 and May 1991, were
identified prospectively and interviewed with a structured
questionnaire. A total of 161 men diagnosed with benign
prostatic hypertrophy and 164 non-urological hospital controls
were given identical questionnaires. The questionnaire covered
a wide range of factors identified from previous studies, but
the central hypotheses for this study related to diet (fat and
green vegetables), sexual activity and farming as an
occupation. This study found no association between farming
and risk of prostatic cancer (odds ratio = 0.74, 95%
confidence interval 0.46-1.18), nor with sexual activity as
measured by number of sexual partners (chi-squared test for
trend P = 0.52). A history of sexually transmitted disease was
not significantly associated with prostatic cancer, but the
numbers involved were very small and the odds ratio of 2.06
(0.38-11.2) is consistent with the hypothesis. A range of
questions aimed at eliciting dietary fat intake produced no
significant associations, although meat consumption showed
increasing risk with increasing consumption (test for trend P
= 0.005). Increased consumption of leafy green vegetables
was associated with lower risk, but not significantly so
(test for trend P = 0.16). As expected with so many factors
investigated, some statistically significant associations were
found, although these can only be viewed as hypothesis
generating in this context. These included apparent protective
effects of circumcision and high fish consumption.
Usefulness of PSA density and PSA excess in the
differential diagnosis between prostate cancer and benign
prostatic hypertrophy.
Diaz F; Morell M; Rojo G
Urology Department, Carlos Haya Regional Hospital, Malaga,
Spain.
Int J Biol Markers (Italy) Jan-Mar 1996, 11 (1)
p12-7
The usefulness of PSA density (PSAD) was evaluated in
relation to the volume of the transitional zone (PSAT) and PSA
excess. With this purpose we conducted a study including 27
patients diagnosed as having prostatic cancer (PC) and 46
patients with benign prostatic hypertrophy (BPH). In all of
them, the PSA concentration in the serum was determined as
well as the total prostatic volume and the transitional zone
volume; digital rectal examination (DRE) was also performed.
The major diagnostic efficacy was obtained with the excess of
PSA (73%, cutoff = -13 ng/ml), followed by DRE (68%), PSAT
(64%, cutoff = 0.5), PSAD (64%, cutoff = 0.2), and lastly PSA
and ultrasonography (60%). Multivariate analysis (logistic
regression) demonstrated PSA excess and DRE to be the best
predictors. The model obtained by regression shows the best
positive predictive value, and PSA excess the best negative
predictive value. Consequently, PSA excess could be relevant
in prostate cancer diagnosis.
[Detection of prostate cancer in urological
practice: clinical establishment of serum PSA reference values
by age]
Yamazaki H; Suzuki Y; Madarame A; Katoh N; Masuda F; Ohishi;
Endo K
Department of Urology, Jikei Daisan Hospital, Tokyo,
Japan.
Nippon Hinyokika Gakkai Zasshi (Japan) Mar 1996, 87 (3)
p702-9
BACKGROUND: Determinations of serum levels of prostate
specific antigen (PSA) are widely used for the detection of
prostate cancer, but have not demonstrated sufficient
sensitivity and specificity to be useful in urological
practice. In order to enhance the diagnostic value of serum
PSA, we studied the distribution of serum PSA levels by age in
urological patients without clinical evidence of prostate
cancer and determined clinical PSA reference values by age
decades.
METHODS: The study included a total of 590 male patients
aged 40 to 89 years who visited our urological clinic
complaining of voiding symptoms from January 1991 to October
1994, but had no clinically evident prostate cancer. We
defined patients to be without clinical evidence of prostate
cancer if they had negative test results in digital rectal
examination, ultrasonography, and serum PSA assay, or had
positive test results in one or more of these tests but had a
nonmalignant prostate biopsy. Serum PSA levels were measured
by E-Test Tosoh II (AIA-PACK PA, normal range; 0 to 5.3
ng/ml). The patients were grouped by age decades and serum PSA
values were given as percentiles.
RESULTS: Analyzed by Pearson's correlation coefficient,
serum PSA levels were correlated significantly with patient
age (r = 0.24, p < 0.001). Prostatic volume was correlated
weakly but significantly with patient age (r = 0.12, p =
0.005), and PSA density was also correlated significantly with
patient age (r = 0.20, p < 0.001). Thus, serum PSA levels
were demonstrated to increase with advancing patient age.
Factors other than benign prostatic hypertrophy were also
suggested to explain the increase in serum PSA levels in older
patients. With the 95th percentile for serum PSA as the upper
limit, the clinical PSA reference values by age decades were
determined to be 2.6 ng/ml for patients aged 40 to 49 years,
5.0 ng/ml for 50 to 59 years, 7.5 ng/ml for 60 to 69 years,
10.1 ng/ml for 70 to 79 years, and 12.4 ng/ml for 80 to 89
years.
CONCLUSION: We found a significant increase in serum PSA
levels with advancing patient age. Thus, it is appropriate to
have serum PSA reference values by age decades. Prospective
clinical trials are necessary to define the usefulness of the
PSA reference values by patient age in urological
practice.
Free-to-total prostate specific antigen ratio as a
single test for detection of significant stage T1c prostate
cancer.
Elgamal AA; Cornillie FJ; Van Poppel HP; Van de Voorde WM;
McCabe R; Baert LV
Department of Urology, University Hospitals of KU Leuven,
Belgium.
J Urol (United States) Sep 1996, 156 (3) p1042-7; discussion
1047-9
PURPOSE: We investigated whether impalpable, invisible
(stage T1c) but significant prostate cancer can be detected
better by determining the free-to-total prostate specific
antigen (PSA) ratio of equivocal PSA serum levels.
MATERIALS AND METHODS: The specificity of free-to-total PSA
ratio using research monoclonal enzyme immunoassays was
compared to that of PSA greater than 4.0 ng./ml. in 117
consecutive patients with PSA 3 to 15 ng./ml. (Hybritech
Tandem-R assay) due to untreated benign prostatic hypertrophy
or prostate cancer. Of the patients 77% underwent adenectomy
or radical prostatectomy with thorough pathological evaluation
of surgical specimens.
RESULTS: Benign prostatic hypertrophy had a greater median
free-to-total PSA ratio than stages T1c and T2 or greater
prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001
and p = 0.0268, respectively). In stage T1c prostate cancer,
areas under receiver operating characteristic curves were 0.58
and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total
PSA ratio correlated with prostate volume (r = 0.49, p =
0.005) and Gleason score (r = -0.37, p = 0.036).
Pathologically, 84% of stage T1c cancers were significant and
comparable to stage T2 or greater cancers.
CONCLUSIONS: Free-to-total PSA ratio enhances the efficacy
of PSA measurement by improving specificity for detecting
impalpable, invisible but significant stage T1c prostate
cancer.
[Transurethral thermotherapy with microwaves in
symptomatic prostatic benign hypertrophy: comparison between
the high-energy (2.5) protocol and the standard protocol
(2.0)]
Mompo Sanchis JA; Paya Navarro JJ; Prosper Rovira F
Centro Medico Urotecno, Clinica Casa de Salud, Valencia,
Espana.
Arch Esp Urol (Spain) Mar 1996, 49 (2) p99-109
OBJECTIVES: The efficacy of three therapeutic protocols of
transurethral microwave thermotherapy (TUMT), was compared in
a study comprised of 355 patients that had been treated for
benign prostatic hypertrophy (BPH) between March, 1992 and
March, 1995.
METHODS: TUMT were performed with the Prostatron device
with intravenous analgosedation and on an outpatient basis. In
the first group (Protocol A), 122 patients received a standard
treatment (Prostasoft 2.0/hour); the second group of 81
patients were included into Protocol B (Prostasoft 2.0/2
hours); 152 patients were treated with higher-energy in
Protocol C (Prostasoft 2.5/1 hour). The number of sessions
(635) performed were based on prostatic length: L < 45 mm -
one session (Prostanec catheter); L < 55 mm - two sessions
(additional black catheter session); L < 65 mm - three
session (additional white catheter session).
RESULTS: All groups improved significantly for subjective
symptoms (symptom score) and objective parameters (peak flow,
residual urine). Comparison of the results between the three
groups at 6 and 12 months showed a significantly better
clinical outcome in protocol C >> B > A: Morbidity
was higher in group C than in group B than in group A.
CONCLUSION: Our results indicate that transurethral
microwave thermotherapy is a safe and effective procedure
which improves objective and subjective parameters. Better
outcomes were obtained with long session times (2H) and
overall higher energy (2.5) input, which may be explained by
the creation by cavities within the prostate, but at the cost
of increased morbidity. However, TUMT can still be delivered
as an anesthesia-free and outpatient non-surgical alternative
treatment for BPH.
Two-dimensional outcome analysis as a guide for
quality assurance of prostatectomy.
Cohen YC; Olmer L; Mozes B
Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer,
Sackler Faculty of Medicine, Tel Aviv University,
Israel.
Int J Qual Health Care (England) Feb 1996, 8 (1)
p67-73
PURPOSE: To find outlier centers in different aspects of
quality of care by comparing two different outcomes and
adjusting to case mix in benign prostatic hypertrophy (BPH)
patients undergoing prostatectomy.
MATERIALS AND METHODS: An observational study including 537
consecutive patients undergoing prostatectomy for BPH in three
medical centers in Israel between 1991 and 1992. Data were
collected from medical charts and by a structured interview.
Outcomes examined included immediate surgical complications
and postoperative symptom effect level. Regression analysis
was employed to adjust for case mix and to determine the
additional contribution of medical centers.
RESULTS: We found significant variability among centers in
crude symptom effect, but not after case mix adjustment. An
outlier was detected in both the crude and case mix-adjusted
urological complications.
CONCLUSIONS: Centers may differ with various outcomes. This
may reflect variability in different levels of performance
within different aspects of the process of care in
prostatectomy procedures.
Alpha blockers: a reassessment of their role in
therapy.
Cauffield JS; Gums JG; Curry RW Jr
University of Florida College of Medicine, Gainesville,
USA.
Am Fam Physician (United States) Jul 1996, 54 (1)
p263-6
Intended for the treatment of hypertension, alpha blockers
offer advantages in treating patients who also have other risk
factors for coronary artery disease. Alpha blockers lower
blood pressure by decreasing vascular resistance and are
effective for the treatment of mild to moderate hypertension.
In addition, alpha blockers have beneficial effects on lipid
levels; they increase high-density lipoprotein levels and
decrease total cholesterol, low-density lipoprotein and
triglyceride levels. Alpha blockers do not induce glucose
intolerance or hyperinsulinemia. Although they appear to
decrease left ventricular mass, the clinical significance of
this action is unknown. Alpha blockers are also effective for
improving the symptoms of benign prostatic hypertrophy,
although surgery is recommended for patients with severe
symptoms. (22 Refs.)
Effect of prostatic growth factor, basic fibroblast
growth factor, epidermal growth factor, and steroids on the
proliferation of human fetal prostatic fibroblasts.
Luo D; Lin Y; Liu X; Qin Z; Zhao C; Zhang Y; Yu Z
Department of Biochemistry, Shandong Medical University,
Jinan, People's Republic of China.
Prostate (United States) Jun 1996, 28 (6) p352-8
To study the relationship between androgen metabolism and
the pathogenesis of benign prostatic hypertrophy, we purified
a growth factor from benign hyperplastic tissue of human
prostates and assayed the proliferative responses of human
fetal prostatic fibroblasts to the purified growth factor
(hPGF), basic fibroblast growth factor (bFGF), epidermal
growth factor (EGF), dihydrotestosterone (DHT), and estradiol
(E2). Prostatic tissue extracts were fractionated using
heparin-Sepharose chromatography. The fraction that eluted
with 1.3-1.7 M NaCl contained the majority of mitogenic
activity. Sodium dodecyl sulfate polyacrylamide gel
electrophoresis (SDS/PAGE) of the lyophilyzed active fraction
showed a band at 17,000 daltons. Human prostatic fibroblasts
were isolated from fetal prostate and tested for their
proliferative responses to hPGF, bFGF, EGF, DHT, and E2. hPGF,
as well as bFGF and EGF, did increase tritiated thymidine
incorporation into the cultured fibroblasts. DHT(10(-7) M) had
a significant stimulatory effect on cell growth in serum-free
media after 6 days of culture. E2(10-7 M) had no effect on
cell proliferation. The combination of DHT and E2 showed no
synergistic effect. We conclude that our purified hPGF, bFGF,
and EGF promote cell growth directly, DHT indirectly, while E2
does not. The effect of DHT appears to be mediated via the
increased production and/or secretion of growth factor(s).
Possibly, the bFGF-like hPGF purified from human benign
hyperplastic prostatic tissue is such a mediator.
The impact of prostate-specific antigen density in
predicting prostate cancer when serum prostate-specific
antigen levels are less than 10 ng/ml.
Akdas A; Tarcan T; Turkeri L; Cevik I; Biren T; Ilker Y
Department of Urology, Marmara University School of Medicine,
Istanbul, Turkey.
Eur Urol (Switzerland) 1996, 29 (2) p189-92
OBJECTIVE: To evaluate the impact of prostate-specific
antigen density (PSAD) when serum levels of prostate-specific
antigen (PSA) are less than 10 ng/ml.
METHODS: We retrospectively analyzed 134 patients who
underwent transrectal ultrasound (TRUS)-guided prostate
biopsies according to Cooner's algorithm.
RESULTS: Histopathological examination revealed prostate
cancer (PCa) in 22 (16%) and benign prostatic hypertrophy
(BPH) in 112 (84%) patients. Five patients (23%) with PCa had
PSAD < 0.15 of whom 3 had PSA < 4 ng/ml and 2 had PSA
between 4 and 10 ng/ml. In the BPH group, 60 patients (54%)
had PSAD below 0.15 whereas 52 patients (46%) had PSAD over
0.15. With 0.15 as the cutoff level of PSAD, the sensitivity
and specificity of PSAD was found as 77 and 54%, respectively.
In this patient population, PSA with the cutoff level of 4
ng/ml has sensitivity and specificity levels of 77 and 33%,
respectively. According to these results, a statistically
significant difference was found between PSA and PSAD only in
terms of diagnostic specificity (chi-square, p < 0.05).
There were 29 patients with negative digital rectal
examination (DRE) and TRUS and PSA 4-10 ng/ml who underwent
biopsy because of PSAD > 0.15. No cancer was detected in
this group of patients, suggesting that biopsy in this
subgroup may be unnecessary.
CONCLUSION: Although PSAD seemed to increase the
specificity without any decrease in sensitivity in the
diagnosis of prostate cancer, it did not bring any practical
advantage in our selected population since all PCa cases had
abnormal DRE and/or TRUS findings.
Usefulness of prostate-specific antigen density as
a diagnostic test of prostate cancer.
Filella X; Alcover J; Molina R; Carrere W; Carretero P;
Ballesta AM
Department of Clinical Biochemistry, (Unit Cancer Research),
Hospital Clinic i Provincial, Barcelona, Spain.
Tumour Biol (Switzerland) 1996, 17 (1) p20-6
To evaluate the diagnostic usefulness of prostate-specific
antigen density (PSAD) in prostate cancer (PC)
prostate-specific antigen (PSA) concentrations were measured
in 175 patients with benign prostatic hypertrophy (BPH) and 50
patients with PC. Patients with BPH were classified according
to the presence of complications of the disease: urinary
infection or the presence of a bladder catheter. PSAD levels
were observed to be greater than 0.15 in 3% of the patients
with uncomplicated BPH and in 40% of the patients with
complicated BPH. PSA levels were higher than 10 micrograms/l
in 3 and 27% of these patients, respectively. High levels of
PSAD were observed in 80% of the patients with cancer.
Sixty-four percent of the patients with cancer presented PSA
levels greater than 10 micrograms/l. These results indicate
that PSAD is a useful parameter in the differential diagnosis
of PC and BPH with the diagnostic efficacy of PSAD being
greater than that of the serum determination of PSA..
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