While symptoms clusters are practical groupings helpful to elucidate disease causes and suggesting treatment options, clinical phenotyping is supposed to be a more precise indication of underlying genetical differences. An attempt to phenotype CPPS sufferers have been made by Shoskes et al (2009) (1-2). In my opinion their approach is more like a mix of symptom clusters, select clinical findings and co-morbidities. They suggest six groups: urologic (essentialy the micturition & genito-urinary symptom clusters), psychosocial (more or less sickness behavior), organ specific (clinical findings about the prostate and ejaculate), infection (clinical findings about bacteria), neurological/systemic (essentially the remaining symptom clusters in my previous posts) and muscle tenderness. Although useful I am of the opinion that their categories are a bit too rough and disparate to be useful for research, but they may be helpful in improving the treatment of patients.
And an evaluation just agreed with me. The author concluded that "a weak or lacking correlation with the studied clinical parameters suggest that further development is required".(3)
Other researchers (Anderson et al, and Dimitrakov et al) have focused on profiling of HPA function and hormonal testing, both of which will be discussed under the findings chapters.
Updated 2009-09-04
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, klinisk fenotypning
_____________
(1) Shoskes DA, Nickel JC, Rackley RR, Pontari MA. Clinical phenotyping in CP/CPPS and IC: a management strategy for urologic chronic pelvic pain syndromes. Prostate Cancer Prostatic Dis 2008, 7pp.
(2) Shoskes DA, Nickel JC, Dolinga R, Prots D. Clinical phenotyping in CP/CPPS and correlation with symptom severity. Urology 73(3):538-542, 2009.
(3) Hedelin HH. Evaluation of a modification of the UPOINT clinical phenotype system for the CPPS. Scand J Urol Nephrol 9:1-4, aug 2009 (epub ahead of print).
Thursday, April 30, 2009
Wednesday, April 29, 2009
Socio-economic differences and education
No or small differences in incidence due to economic or education level differences have been found, although lower socio-economic status (SES) predict that symptoms will be experienced as worse / more painful (1). Why this difference in experience? Two causes are probable: a) worse nutrition and more stress caused by the lower SES causing an objectively more severe disease, or b) subjectively experiencing being more ill.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
__________________
(1) McNaughton Collins M, Pontari MA, O'Leary MP, Calhoun EA, Santanna J, Landis JR, Kusek JW, Litwin MS,.Quality of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network.J Gen Intern Med 16(10):656-662, 2001.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
__________________
(1) McNaughton Collins M, Pontari MA, O'Leary MP, Calhoun EA, Santanna J, Landis JR, Kusek JW, Litwin MS,.Quality of life is impaired in men with chronic prostatitis: the Chronic Prostatitis Collaborative Research Network.J Gen Intern Med 16(10):656-662, 2001.
Saturday, April 25, 2009
Leukocytes, urates and citrates
Leukocyte (white blood cells) counts and common inflammatory markers have little or no correlation with CP/CPPS. Whether this be in urine (VB3), semen and or prostatic secretions. Cytokines show better correlation. See further discussion below in the sections on micro-organisms and inflammation.
Urates and other compounds typical for urine have been found in the prostate and prostatic calculi indicating reflux.
Added 2009-04-26
Various small studies have found a correlation between expressed prostatic secretion and semen contents of uric acid (urates) and CPPS symptoms. The assumption is that uric acid (urates) cause an inflammatory reaction and that the presence of uric acid is caused by reflux. (1-3)
Reflux, or retrograde flow, is the "backflow" of urine towards the prostate or kidney instead of out of the body. Causes of reflux are either "uncoordinated muscules" (dyssynergia) or physical abnormalities or urinary tract infections.
Citrate levels may be decreased in CPPS sufferers. (4)
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, urater, urinreflux
______________
(1) Persson BE, Ronquist G. Evidence for a mechanistic association between nonbacterial prostatitis and levels of urate and creatinine in expressed prostatic secretion. J Urol. 155(3):958-60, 1996.
(2) Hou BS, Xia XY, Pan LJ, Yang B, Shao Y, Shang XJ, Yao B, Cui YX, Huang YF. [Determination of uric acid in the expressed prostatic secretion of chronic prostatitis patients and its clinical significance]. Zhonghua Nan Ke Xue 14(3):245-7, 2008. Summary only, article in Chinese.
(3) Motrich RD, Olmedo JJ, Molina R, Tissera A, Minuzzi G, Rivero VE. Uric acid crystals in the semen of a patient with symptoms of chronic prostatitis. Fertil Steril. 85(3):751.e1-751.e4. 2006.
(4) Chen J, Xu Z, Zhao H, Jiang X. Citrate in expressed prostatic secretions has the feasibility to be used as a useful indicator for the diagnosis of category IIIB prostatitis. Urol Int. 78(3):230-4, 2007.
and
Chen J, Zhao HF, Xu ZS. The prostate has secretory dysfunction for category IIIA and IIIB prostatitis. J Urol. 177(6):2166-9, 2007.
Urates and other compounds typical for urine have been found in the prostate and prostatic calculi indicating reflux.
Added 2009-04-26
Various small studies have found a correlation between expressed prostatic secretion and semen contents of uric acid (urates) and CPPS symptoms. The assumption is that uric acid (urates) cause an inflammatory reaction and that the presence of uric acid is caused by reflux. (1-3)
Reflux, or retrograde flow, is the "backflow" of urine towards the prostate or kidney instead of out of the body. Causes of reflux are either "uncoordinated muscules" (dyssynergia) or physical abnormalities or urinary tract infections.
Citrate levels may be decreased in CPPS sufferers. (4)
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, urater, urinreflux
______________
(1) Persson BE, Ronquist G. Evidence for a mechanistic association between nonbacterial prostatitis and levels of urate and creatinine in expressed prostatic secretion. J Urol. 155(3):958-60, 1996.
(2) Hou BS, Xia XY, Pan LJ, Yang B, Shao Y, Shang XJ, Yao B, Cui YX, Huang YF. [Determination of uric acid in the expressed prostatic secretion of chronic prostatitis patients and its clinical significance]. Zhonghua Nan Ke Xue 14(3):245-7, 2008. Summary only, article in Chinese.
(3) Motrich RD, Olmedo JJ, Molina R, Tissera A, Minuzzi G, Rivero VE. Uric acid crystals in the semen of a patient with symptoms of chronic prostatitis. Fertil Steril. 85(3):751.e1-751.e4. 2006.
(4) Chen J, Xu Z, Zhao H, Jiang X. Citrate in expressed prostatic secretions has the feasibility to be used as a useful indicator for the diagnosis of category IIIB prostatitis. Urol Int. 78(3):230-4, 2007.
and
Chen J, Zhao HF, Xu ZS. The prostate has secretory dysfunction for category IIIA and IIIB prostatitis. J Urol. 177(6):2166-9, 2007.
General findings
In addition to patient self-reported symptoms various standard tests are performed to check for patient health (e.g. PSA test), bacteria and hyperplasia. All these are usually negative or within the normal range. The CPPS patient is 'healthy and well' despite pain, tiredness, frequency etc. And that quality of life is affected by conditions affecting micturition has been concluded repeatedly(1). It may be noted that older men with LUTS (lower urinary tract symptoms)(2) seem more prone to injuries from falls.(3)
________________________
(1) E.g. Coyne KS, Sexton CC, Irwin DE, Kopp ZS, Kelleher CJ, Milsom I. The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study. BJU Int. 2008 Jun;101(11):1388-95. And Bernardes J, Cameron E, Dunn P."A summary report on the impact of Prostatitis and Benign Prostatic Hyperplasia on men's lives and those of their families", discussions on self-help group message boards etc.
(2) This is a borderline wastebasket term. For a fuller discussion see:
Chapple CR, Wein AJ, Abrams P, Dmochowski RR, Giuliano F, Kaplan SA, McVary KT, Roehrborn CG. Lower urinary tract symptoms revisited: a broader clinical perspective. Eur Urol 54(3):563-569, 2008.
(3) Kellogg Parsons J, Mougey J, Lambert L, Wilt TJ, Fink HA, Garzotto M, Barrett-Connor E, Marshall LM. Lower urinary tract symptoms increase the risk of falls in older men. BJU Int. 2009 Jan 9. [Epub ahead of print]
________________________
(1) E.g. Coyne KS, Sexton CC, Irwin DE, Kopp ZS, Kelleher CJ, Milsom I. The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study. BJU Int. 2008 Jun;101(11):1388-95. And Bernardes J, Cameron E, Dunn P."A summary report on the impact of Prostatitis and Benign Prostatic Hyperplasia on men's lives and those of their families", discussions on self-help group message boards etc.
(2) This is a borderline wastebasket term. For a fuller discussion see:
Chapple CR, Wein AJ, Abrams P, Dmochowski RR, Giuliano F, Kaplan SA, McVary KT, Roehrborn CG. Lower urinary tract symptoms revisited: a broader clinical perspective. Eur Urol 54(3):563-569, 2008.
(3) Kellogg Parsons J, Mougey J, Lambert L, Wilt TJ, Fink HA, Garzotto M, Barrett-Connor E, Marshall LM. Lower urinary tract symptoms increase the risk of falls in older men. BJU Int. 2009 Jan 9. [Epub ahead of print]
Saturday, March 28, 2009
Seasonality etc part 2
Why these cycles? It is not uncommon in disease.
Many disorders show seasonality, but it is seldom explained. In an article in Medical hypotheses the authors (1) suggest that “temporal variations of autonomic balance” affect disease. What they essentially suggest is an expansion of the Th1/Th2 balance hypothesis of disease (which is a convenient simplification). If the immune system is over-balanced towards Th1 response (aka parasympathetic activity, Th1 bias, innate or [intra-]cellular immunity) it supposedly responds well to cancer cells, viruses, yeasts and intracellular pathogens but less well to extracellular pathogens. On the other hand auto-immune disease is more common.
If on the other hand immune response is prevalently Th2 (aka sympathetic activity, Th2 bias, adaptive or humoral immunity) it combats bacteria and extracellular organisms. But allergy and asthma is more common.
Th1/Th2 response shows a circadian rhythm with Th1 prevalence during sleep and Th2 prevalence during daytime. Diseases more common / worse during daytime (thus worsening because of increased Th2 and decreased Th1 response) are e.g. stroke, arrhythmias, seizures, sepsis and asthma. A seasonal pattern of increased Th2 bias during winter and Th1 bias during summer is also postulated.
Disease disrupting sleep will dampen Th1 response and thus worsen disorders affected by this.
They also suggest that Th1 bias is stronger in childhood and senescence (old age).
Their ideas are interesting as CPPS causes sleep disruption, remits during summer and is more common in mid-life. All of which suggest that Th2 bias worsens CPPS.
I’ll get back to this topic when discussing vitamin D, sleep and the HPA axis.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, biologiska rytmer, Th1/Th2-balans
_________________
(1) Medical Hypotheses 63(1):155-177, 2004. Articles by AJ Yun, PY Lee and KA Bazar.
Many disorders show seasonality, but it is seldom explained. In an article in Medical hypotheses the authors (1) suggest that “temporal variations of autonomic balance” affect disease. What they essentially suggest is an expansion of the Th1/Th2 balance hypothesis of disease (which is a convenient simplification). If the immune system is over-balanced towards Th1 response (aka parasympathetic activity, Th1 bias, innate or [intra-]cellular immunity) it supposedly responds well to cancer cells, viruses, yeasts and intracellular pathogens but less well to extracellular pathogens. On the other hand auto-immune disease is more common.
If on the other hand immune response is prevalently Th2 (aka sympathetic activity, Th2 bias, adaptive or humoral immunity) it combats bacteria and extracellular organisms. But allergy and asthma is more common.
Th1/Th2 response shows a circadian rhythm with Th1 prevalence during sleep and Th2 prevalence during daytime. Diseases more common / worse during daytime (thus worsening because of increased Th2 and decreased Th1 response) are e.g. stroke, arrhythmias, seizures, sepsis and asthma. A seasonal pattern of increased Th2 bias during winter and Th1 bias during summer is also postulated.
Disease disrupting sleep will dampen Th1 response and thus worsen disorders affected by this.
They also suggest that Th1 bias is stronger in childhood and senescence (old age).
Their ideas are interesting as CPPS causes sleep disruption, remits during summer and is more common in mid-life. All of which suggest that Th2 bias worsens CPPS.
I’ll get back to this topic when discussing vitamin D, sleep and the HPA axis.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb, biologiska rytmer, Th1/Th2-balans
_________________
(1) Medical Hypotheses 63(1):155-177, 2004. Articles by AJ Yun, PY Lee and KA Bazar.
Counter indications part 2 -- why alcohol, caffeine and citrus?
I cannot but speculate, but all of these have in common that they affect vasopressin levels and the CNS.
Alcohol (ethanol)
“Humans have practiced the art of fermentation for millennia, observing the many actions of ethanol on physiology and behavior in the process. Despite our familiarity with ethanol, we have remarkably little insight into the mechanisms by which it reduces inhibitions and anxiety, nor do we know much about how it produces signs of more severe intoxication.” (1)
What is known is that ethanol affects plasma AVP concentrations thus affecting water balance. Ethanol does also affect the HPA axis in other ways modulating the release of e.g. adrenocorticotropic hormone (ACTH) and corticosterone (CORT)(2) and human growth hormone (hGH). The latter is interesting as acute application of GH results in a reduced urinary electrolyte and water excretion(3), while alcohol suppresses hGH secretion and LH, FSH, testosterone, estradiol etc.
Coffee, tea and chocolate (caffeine)
Caffeine has been shown to induce relaxation and increased alertness and cognition in lower doses, as well as anxiety and nervousness as dosage increases. Even panic attacks in individuals with high anxiety (Bourin et al. 1998). Caffeine also increases corticosterone, cortisol and ACTH levels.
Citrus fruits
It is intriguing that citrus fruit would affect CPPS. Current hypothesis suggest that citrus fruit act as irritants in the bladder. New research suggest that apigenin (a bioflavonoid found in citrus fruits, but also e.g. celery and parsley) may affect the CNS (HPA-axis). Murine tests has e.g. shown it to affect dopamine and serotonin, and to decrease serum corticosterone levels.(4) Other research indicate that it "inhibits the proliferation of prostatic stromal cells"(5), i.e. may inhibit the development of benign prostatic hyperplasia. Is there enough apigenin in eaten citrus etc to have any effects? Further research is needed.
Added nov 18 2009:
As vitamin C deficiency causes diminished thrombosis and fibrinolysis (blood clotting) a speculative cause for citrus exacerbations may be improved blood clotting ability. Especially as most successful CPPS treatments seem to decrease the propensity for blood clotting.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
________________
(1) Harris RA, Trudell JR, Mihic SJ. Ethanol's molecular targets. Sci Signal. 1(28):re7, 2008. (I liked the introduction to their report.)
(2) Haddad JJ. Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. Biochem Biophys Res Commun. 323(2):361-71, 2004.
(3) Dimke H, Flyvbjerg A, Frische S. Acute and chronic effects of growth hormone on renal regulation of electrolyte and water homeostasis. Growth Horm IGF Res. 17(5):353-68, 2007
(4) Yi LT, Li JM, Li YC, Pan Y, Xu Q, Kong LD. Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin. Life Sci 82(13-14):741-751, 2008.
(5) Bektic J, Guggenberger R, Spengler B, Christoffel V, Pelzer A, berger AP, Ramoner R, Bartsch G, Klocker H. The flavonoid apigenin inhibits the proliferation of stromal cells via the MAPK pathway and cell-cycle arrest in G1/S. Maturitas 55(S1):S37-46, 2006.
Alcohol (ethanol)
“Humans have practiced the art of fermentation for millennia, observing the many actions of ethanol on physiology and behavior in the process. Despite our familiarity with ethanol, we have remarkably little insight into the mechanisms by which it reduces inhibitions and anxiety, nor do we know much about how it produces signs of more severe intoxication.” (1)
What is known is that ethanol affects plasma AVP concentrations thus affecting water balance. Ethanol does also affect the HPA axis in other ways modulating the release of e.g. adrenocorticotropic hormone (ACTH) and corticosterone (CORT)(2) and human growth hormone (hGH). The latter is interesting as acute application of GH results in a reduced urinary electrolyte and water excretion(3), while alcohol suppresses hGH secretion and LH, FSH, testosterone, estradiol etc.
Coffee, tea and chocolate (caffeine)
Caffeine has been shown to induce relaxation and increased alertness and cognition in lower doses, as well as anxiety and nervousness as dosage increases. Even panic attacks in individuals with high anxiety (Bourin et al. 1998). Caffeine also increases corticosterone, cortisol and ACTH levels.
Citrus fruits
It is intriguing that citrus fruit would affect CPPS. Current hypothesis suggest that citrus fruit act as irritants in the bladder. New research suggest that apigenin (a bioflavonoid found in citrus fruits, but also e.g. celery and parsley) may affect the CNS (HPA-axis). Murine tests has e.g. shown it to affect dopamine and serotonin, and to decrease serum corticosterone levels.(4) Other research indicate that it "inhibits the proliferation of prostatic stromal cells"(5), i.e. may inhibit the development of benign prostatic hyperplasia. Is there enough apigenin in eaten citrus etc to have any effects? Further research is needed.
Added nov 18 2009:
As vitamin C deficiency causes diminished thrombosis and fibrinolysis (blood clotting) a speculative cause for citrus exacerbations may be improved blood clotting ability. Especially as most successful CPPS treatments seem to decrease the propensity for blood clotting.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
________________
(1) Harris RA, Trudell JR, Mihic SJ. Ethanol's molecular targets. Sci Signal. 1(28):re7, 2008. (I liked the introduction to their report.)
(2) Haddad JJ. Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. Biochem Biophys Res Commun. 323(2):361-71, 2004.
(3) Dimke H, Flyvbjerg A, Frische S. Acute and chronic effects of growth hormone on renal regulation of electrolyte and water homeostasis. Growth Horm IGF Res. 17(5):353-68, 2007
(4) Yi LT, Li JM, Li YC, Pan Y, Xu Q, Kong LD. Antidepressant-like behavioral and neurochemical effects of the citrus-associated chemical apigenin. Life Sci 82(13-14):741-751, 2008.
(5) Bektic J, Guggenberger R, Spengler B, Christoffel V, Pelzer A, berger AP, Ramoner R, Bartsch G, Klocker H. The flavonoid apigenin inhibits the proliferation of stromal cells via the MAPK pathway and cell-cycle arrest in G1/S. Maturitas 55(S1):S37-46, 2006.
Tuesday, March 17, 2009
Managment, evaluation and differential diagnosis
Below follows an overview of the current management recomendations (1-3) [and personal experience]. The obvious goal of the procedure is to exclude other possible conditions with similar presentation to CPPS.
The standard procedure is to:
Some optional procedures are also recommended. These are semen analysis (especially if the patient is young and can be expected to want children), urethral swab (to search for micro-organisms), flow-EMG, cystoscopy (e.g. if IC is suspected) and MRI / CAT-scan / X-rays (especially on suspiscion of cancer). If CPPS is assumed an in-depth evaluation of pain, sexual discomfort, dysuric discomfort, abdominal-pelvic status and muscular tone (“pelvic floor assessment”) should also be made (by palpation).
Conditions to differentiate from (the list is not to be regarded as a complete listing):
Do also see discussion on co-morbidities that will follow later.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
___________________
(1) Potts J, Payne RE. Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient classification is key. Cleveland Clinic Journal of Medicine, vol. 74, suppl 3, May 2007.
(2) Nickel JC. Recommendations for the evaluation of patients with prostatitis. World J Urol 21:75-81, 2003.
(3) Nickel JC, Baranowski AP, Pontari M, Berger RE, Tripp DA. Managment of men diagnosed with CP/CPPS who have failed traditional management. Reviews in Urology 9(2):63-72, 2007.
The standard procedure is to:
- take an anamnesis (ambition varies, but used medications, previous surgery and treatment directed at the lower abdomen and pelvis should be checked for),
- do some tests (PSA, standard blood, urinalysis and presence of STD),
- palpate the prostate and testicles and
- give anti-biotics (e.g. ciprofloxacin), anti-inflammatories and alpha-blockers.
Some optional procedures are also recommended. These are semen analysis (especially if the patient is young and can be expected to want children), urethral swab (to search for micro-organisms), flow-EMG, cystoscopy (e.g. if IC is suspected) and MRI / CAT-scan / X-rays (especially on suspiscion of cancer). If CPPS is assumed an in-depth evaluation of pain, sexual discomfort, dysuric discomfort, abdominal-pelvic status and muscular tone (“pelvic floor assessment”) should also be made (by palpation).
Conditions to differentiate from (the list is not to be regarded as a complete listing):
- Abdominal wall defects: inguinal or ventral wall hernias, myofascial trigger points.
- Gastrointestinal causes: appendicitis, diverticulitis, constipation, anal fissures, hemorrhoids. [Do notice that constipation may occur in CPPS!]
- Infection: sexually transmitted diseases, chronic bacterial prostatitis, fungal infection.
- Musculoskeletal causes: neoplasm (primary or metastatic), degenerative joint disease of the hips, sacroileitis.
- Neurologic causes: low thoracic or lumbar herniated nucleus pulposis, lumbar stenosis, Parkinson disease, diabetic cystopathy, demyelinating disease.
- Urologic causes: urinary retention, prostatic abcess, renal calculi, varicocele, epididymitis, testicular neoplasm, interstitial cystitis, bladder outlet obstruction, bladder neck hypertrophy, vesical sphincter dyssynergia, prostatic cysts, kidney disease.
- And of course prostate cancer and BPH.
Do also see discussion on co-morbidities that will follow later.
Andra bloggar om CPPS, kroniskt bäckenbottensmärtsyndrom, kronisk abakteriell prostatit, NIHIIIb
___________________
(1) Potts J, Payne RE. Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient classification is key. Cleveland Clinic Journal of Medicine, vol. 74, suppl 3, May 2007.
(2) Nickel JC. Recommendations for the evaluation of patients with prostatitis. World J Urol 21:75-81, 2003.
(3) Nickel JC, Baranowski AP, Pontari M, Berger RE, Tripp DA. Managment of men diagnosed with CP/CPPS who have failed traditional management. Reviews in Urology 9(2):63-72, 2007.
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