Randhawa, Jaskirat | Jhaveri, Jay | Ghannam, Suzanne | Donnelly, Christopher | Pinkhasov, Ruben | Lee, Michael | Shabsigh, Ridwan
Journal of Urology, ISSN: 0022-5347, Vol: 185, Issue: 4, Date: 2011-04-01, Start page: e528, # of pages: 1
Friday, June 10, 2011
Friday, April 1, 2011
What is the minimum or obligatory urine output in a day for healthy kidneys?
The minimum urine output necessary / day = the amount of urine required to excrete "the solute load" consumed each day.
In an average individual the minimum Solute load excreted daily by kidney is 600-800 mOsm/day. As we know in healthy person, the Maximum urine-concentrating capacity of kidneys is 1200 mOsm/L.
We can calculate the Obligatory urine output in healthy individuals.
for 1200 mOsm solute excretion, the min. amount of urine output required is 1 Liter.
for 600 mOsm solute excretion, the min. amount of urine output will be 0.5 Liter.
Therefore, we require a minimum 500ml of obligatory urine output to excrete daily solute load from our body.
In an average individual the minimum Solute load excreted daily by kidney is 600-800 mOsm/day. As we know in healthy person, the Maximum urine-concentrating capacity of kidneys is 1200 mOsm/L.
We can calculate the Obligatory urine output in healthy individuals.
for 1200 mOsm solute excretion, the min. amount of urine output required is 1 Liter.
for 600 mOsm solute excretion, the min. amount of urine output will be 0.5 Liter.
Therefore, we require a minimum 500ml of obligatory urine output to excrete daily solute load from our body.
New Treatment Buzz for Hepatitis C patients!
Three drug cocktail: Boceprevir + Peg-interferon + Ribavirin (or) Telaprevir + Peg-interferon + Ribavirin has shown promising results in treatment of Hepatitis C patients.
"66% of previously untreated patients treated with the three-drug regimen of boceprevir, peginterferon, and ribavirin cleared the virus for good, compared to 38% of patients treated with peginterferon and ribavirin alone."
In other study in NEJM, 75% of patients treated for "44 weeks achieved sustained viral clearances, compared to 29% of patients who got a second round of peg-interferon and Ribavirin." The results were "similar to those seen in phase III trials of telaprevir."
"66% of previously untreated patients treated with the three-drug regimen of boceprevir, peginterferon, and ribavirin cleared the virus for good, compared to 38% of patients treated with peginterferon and ribavirin alone."
In other study in NEJM, 75% of patients treated for "44 weeks achieved sustained viral clearances, compared to 29% of patients who got a second round of peg-interferon and Ribavirin." The results were "similar to those seen in phase III trials of telaprevir."
Wednesday, February 9, 2011
Role of Testosterone Replacement Therapy in patients diagnosed with prostate cancer ( A review )
INTRODUCTION: The relationship between serum androgens and prostate cancer has been a topic of debate for almost 70 years. Prostate cancer and serum androgens, specifically testosterone, were thought to be directly related. This idea stems from the seminal work of Huggins and Hodges [1] who in 1941 reported the regression of metastatic cancer in 3 men after a reduction in serum testosterone levels, and the progression of metastatic disease and symptoms in one man to whom
exogenous testosterone was given. Since then many studies have been documented some supporting the Testosterone Replacement Therapy (TRT) while others reporting unfavorable outcomes in this target population. We hereby reviewed several
articles to enhance our understanding and work in the favorable direction for the best interest of our patients.
RESULTS: The theory that higher Testosterone leads to enhanced PCa growth has been widely held and continues to inform current medical behavior and recommendations. Morgentaler and Traish [2] reported that there is a limit to the ability of androgens to stimulate Prostate cancer (PCa) growth. A saturation model is proposed; that changes in serum Testosterone (T) concentrations below the point of maximal androgen-AR (androgen receptor) binding will elicit substantial changes in PCa growth, as seen with castration, or with T administration to previously castrated men. Once the maximal androgen-AR binding is reached the presence of additional androgen produces little further effect. The distinction between prior castration and no prior hormonal treatment is critical. Data from a 1981 review from the Memorial Sloan-Kettering Cancer Center [4] revealed that 44 of 48 men with castrate T concentrations developed a rapid “unfavorable response” to daily T injections, most with in 1 month. In contrast, three of four previously untreated men had no early negative response to T administration, and continued to receive daily T injections for 52d, 55d, and 310 d. This difference in response to T administration among hormonally intact men prompted the authors to propose an early version of the saturation hypothesis [2]. ”Normal endogenous testosterone levels may be sufficient to cause near maximal stimulation of prostatic tumors” [4]. They also explained with saturation model why young men, with peak lifetime T concentrations, do not develop massive benign enlargement of the prostate, and do not regularly develop clinical PCa despite the presence of PCa microfoci. [3] In another case report, Morgantaler evaluated response of an 84 y man with untreated PCa treated with T therapy for 2 years. A decline in PSA was noted supporting his
notion that PCa growth may not be adversely affected by changes in serum T beyond the castrate or near-castrate range. [5]
“Impact of serum testosterone on PSA and prostate volume in the General population” Monath et al investigated the relationship of endogenous T concentration on PSA in 150 men without prostate cancer [8]. Mean age was 60.1 years (range 41 to79) and 96% of the men had T concentrations within the normal range. No correlation was found between T and PSA.
A much larger sample (1576 men) from the Massachusetts Male Aging Study also received no correlation between PSA and T concentrations [9].
Bhasin et al administered 600 mg T or placebo weekly for 10 weeks to men ranging in age from 19 to 40 years [10]. Mean PSA did not change significantly from baseline despite T concentration greater than 2800ng/dl in the T treated group.
“Testosterone therapy in men with prostate cancer” Fowler and Whitmore reported [4] unfavorable response to T administration in patients with history of prostate cancer with bony metastasis. However it should be noted that most of these
men were previously castrated or treated with estrogen. Also given the advanced stage of PCa in these men, and lack of a control group; the unfavorable responses may be attributed entirely to the natural history of their disease. Therefore the
limitations of this study have raised questions and the necessity for more comprehensive longitudinal studies.
Piyush K. Aggarwal and Michael G.Oefelein followed 10 hypogoandal patients previously treated with retropubic prostatectomy for organ confined PCa; and administered T. At median of 19 months no patient had detectable PSA and there was significant improvement in hypogonadal symptoms [11]. Similar results are reported by Kaufman et al [12] with T therapy in hypogonadal men who had undergone curative radical prostatectomy.
Pierorazio PM (june 2009) concluded that higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged > 65 y (HR 2.07, 95% confidence interval, CI 1.01-4.23; P=0.047). The study comprised 781 men in Baltimore longitudinal study of aging (636 men with no cancer, 109 with cancer but not high risk, and 36 with high risk cancer) [6]. High risk cancer was defined as death from prostate cancer, PSA level of >=20ng/ml at diagnosis, or Gleason score of >=8. This study questioned many of the previous studies that are done in men with baseline hormonal dysfunction (i.e. hypogonadal men) that might not be representative of the general population, and prevent the formation of universal guidelines or understanding of the disease process. However, the men who developed high-risk prostate cancer were of 7.7 years older at presentation than the remainder (p<0.001). Leibowitz RL et al reviewed records of 96 patients who received high dose T therapy after initial management for prostate cancer [13]. Mean age at diagnosis was 61 (46-85), 60% having PSA <10 ng/ml, 77% having stage T1c-T2 at diagnosis, 72 patients with Gleason score <=7; and median PSA level before TRT 0.1 ng/ml. The retrospective results from 7 years are: 41 men has PSA progression while on TRT, 7 had radiological progression of disease, 56 men discontinued TRT due to increasing PSA levels and 59% of these men had significant reductions in PSA level with no additional intervention; 31 men remained on TRT with no PSA or radiological progression at a median of 36.7 months. In this study nearly 40% patients had no PSA elevations while on T therapy, 60% had increasing PSA and that triggered discontinuation of TRT. In most of patients TRT was not associated with clinical or symptomatic disease progression. DISCUSSION: There is no dispute that androgens have an important role in the development and growth of prostate tissue. The mechanism of action of androgen on prostate tissue has been recently reviewed [14]. Briefly, T enters the prostate cell where it is largely metabolized in the cytoplasm to DHT (Dihydrotestosterone) by the enzyme 5 alpha-reductase [15]. DHT is the primary intraprostatic androgen, as it binds more avidly than T to the Androgen Receptor (AR), which in turn is responsible for mediating androgenic action on the prostate cell. Once bound, the androgen-AR complex translocates to the cell nucleus where it is able to bind directly to DNA, thus exerting its proliferative and trophic effects.
Whether to use T therapy in men with PCa or not is a dilemma for past decades. There is no standardized protocol that a clinician should follow when faced with a symptomatic hypogonadal man with history of prostate cancer. The growing impetus
for reconsidering T therapy stems from many factors, one of which is the increasing recognition of the health benefits of T Therapy in hypogonadal men; including improvements in energy, vitality, sexual desire, erectile function, body composition and bone mineral density [7]. Prostate growth is exquisitely sensitive to variations in androgen concentrations at or below the near–castrate range, but becomes insensitive to changes in androgen concentrations at higher levels [2]. Pierorazio PM et al [6] noted that high or even normal values of serum testosterone might be related to development of high-risk prostate cancer in older men. The authors explained that for younger men androgens might be protective by promoting typical growth and maturation of the prostate, while for older men in whom malignant transformation has occurred, androgens might be harmful by promoting disease progression.
Therefore we are still struggling to answer these questions: Is it reasonable to offer T therapy when some studies showed substantial risk of PCa growth in particular age group [6]. On the other hand, is it ethical to deny a beneficial therapy to hypogonadal patients with PCa when the risk is theoretical and high dose T therapy has not shown progression of disease [2,5].
The decision to start T replacement therapy is also influenced by age of the patient, PSA and serum testosterone levels at start of therapy, stage of PCa at diagnosis, Gleason score, hormonally intactness status, severity of hypogonadal symptoms and feasibility for rigorous surveillance.
CONCLUSION: Testosterone Replacement therapy is beneficial for patients having clinical symptoms of hypogonadism and treatment needs to be individualized focusing on each patient’s benefits and risk. The patient should be explained all the risks of this therapy at the time of consent and needs to be followed with active surveillance of prostate markers. Anytime patient presents with unfavorable symptoms should be considered seriously and a call for withdrawal of therapy is likely warranted. It is also important to recognize the androgen status of each study population, and that high or low serum androgens might have distinct implications in different subpopulations of men (i.e. the hypogonadal vs the eugonadal) at risk of prostate cancer [6].
Again much research needs to be done in this area to enhance our understanding of disease and treatment strategies.
REFERENCES :
1. Huggins C , Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection
on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Jul;168(1):9-12.
2. Eur Urol. 2009 Jul; 56(1):e4; author reply e5. Epub 2009 Apr 1. Re: Abraham Morgentaler, Abdulmaged M. Traish.
Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgendependent
growth. Eur Urol 2009; 55:310-21. PMID: 19349108
3. Sakr WA , Grignon DJ, Crissman JD,et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic
adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo. 1994 May-Jun; 8(3):439-43.
PMID: 7803731
4. Fowler JE Jr , Whitmore WF Jr. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone.
J Urol. 1981 Sep; 126(3):372-5. PMID: 7277602
5. Morgentaler A . Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with
untreated prostate cancer. J Sex Med. 2009 Feb; 6(2):574-7.
6. Pierorazio PM , Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with
aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU Int. 2010 Mar;
105(6):884-5; author reply 885-6. PMID: 19751256
7. Wang C , Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS.
Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and
fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May; 89(5):2085-98. PMID:
15126525
8. Monath JR , McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum testosterone within the normal range do
not affect serum prostate-specific antigen. Urology. 1995 Jul; 46(1):58-61. PMID: 7541587
9. Mohr BA , Feldman HA, Kalish LA, Longcope C, McKinlay JB. Are serum hormones associated with the risk of prostate
cancer? Prospective results from the Massachusetts Male Aging Study. Urology. 2001 May; 57(5):930-5.
10. Bhasin S , Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The
effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul
4; 335(1):1-7.
11. Agarwal PK , Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol. 2005
Feb; 173(2):533-6.
12. Kaufman JM , Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in
hypogonadal men. J Urol. 2004 Sep; 172(3):920-2.
13. Leibowitz RL , Dorff TB, Tucker S, Symanowski J, Vogelzang NJ Testosterone replacement in prostate cancer survivors
with hypogonadal symptoms. BJU Int. 2010 May; 105(10):1397-401. Epub 2009 Nov 11.
14. Tindall DJ , Rittmaster RS. The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of
prostate cancer. J Urol. 2008 Apr; 179(4):1235-42. Epub 2008 Feb 20. Mayo Clinic, Rochester, Minnesota 55905, USA.
tindall@mayo.edu
15. Morgentaler A . Testosterone therapy in men with prostate cancer: scientific and ethical considerations. J Urol. 2009
Mar; 181(3):972-9. Epub 2009 Jan 16.
exogenous testosterone was given. Since then many studies have been documented some supporting the Testosterone Replacement Therapy (TRT) while others reporting unfavorable outcomes in this target population. We hereby reviewed several
articles to enhance our understanding and work in the favorable direction for the best interest of our patients.
RESULTS: The theory that higher Testosterone leads to enhanced PCa growth has been widely held and continues to inform current medical behavior and recommendations. Morgentaler and Traish [2] reported that there is a limit to the ability of androgens to stimulate Prostate cancer (PCa) growth. A saturation model is proposed; that changes in serum Testosterone (T) concentrations below the point of maximal androgen-AR (androgen receptor) binding will elicit substantial changes in PCa growth, as seen with castration, or with T administration to previously castrated men. Once the maximal androgen-AR binding is reached the presence of additional androgen produces little further effect. The distinction between prior castration and no prior hormonal treatment is critical. Data from a 1981 review from the Memorial Sloan-Kettering Cancer Center [4] revealed that 44 of 48 men with castrate T concentrations developed a rapid “unfavorable response” to daily T injections, most with in 1 month. In contrast, three of four previously untreated men had no early negative response to T administration, and continued to receive daily T injections for 52d, 55d, and 310 d. This difference in response to T administration among hormonally intact men prompted the authors to propose an early version of the saturation hypothesis [2]. ”Normal endogenous testosterone levels may be sufficient to cause near maximal stimulation of prostatic tumors” [4]. They also explained with saturation model why young men, with peak lifetime T concentrations, do not develop massive benign enlargement of the prostate, and do not regularly develop clinical PCa despite the presence of PCa microfoci. [3] In another case report, Morgantaler evaluated response of an 84 y man with untreated PCa treated with T therapy for 2 years. A decline in PSA was noted supporting his
notion that PCa growth may not be adversely affected by changes in serum T beyond the castrate or near-castrate range. [5]
“Impact of serum testosterone on PSA and prostate volume in the General population” Monath et al investigated the relationship of endogenous T concentration on PSA in 150 men without prostate cancer [8]. Mean age was 60.1 years (range 41 to79) and 96% of the men had T concentrations within the normal range. No correlation was found between T and PSA.
A much larger sample (1576 men) from the Massachusetts Male Aging Study also received no correlation between PSA and T concentrations [9].
Bhasin et al administered 600 mg T or placebo weekly for 10 weeks to men ranging in age from 19 to 40 years [10]. Mean PSA did not change significantly from baseline despite T concentration greater than 2800ng/dl in the T treated group.
“Testosterone therapy in men with prostate cancer” Fowler and Whitmore reported [4] unfavorable response to T administration in patients with history of prostate cancer with bony metastasis. However it should be noted that most of these
men were previously castrated or treated with estrogen. Also given the advanced stage of PCa in these men, and lack of a control group; the unfavorable responses may be attributed entirely to the natural history of their disease. Therefore the
limitations of this study have raised questions and the necessity for more comprehensive longitudinal studies.
Piyush K. Aggarwal and Michael G.Oefelein followed 10 hypogoandal patients previously treated with retropubic prostatectomy for organ confined PCa; and administered T. At median of 19 months no patient had detectable PSA and there was significant improvement in hypogonadal symptoms [11]. Similar results are reported by Kaufman et al [12] with T therapy in hypogonadal men who had undergone curative radical prostatectomy.
Pierorazio PM (june 2009) concluded that higher levels of serum free testosterone are associated with an increased risk of aggressive prostate cancer among older men. The likelihood of high-risk prostate cancer doubled per unit (0.1) increase in the free testosterone index (FTI) for patients aged > 65 y (HR 2.07, 95% confidence interval, CI 1.01-4.23; P=0.047). The study comprised 781 men in Baltimore longitudinal study of aging (636 men with no cancer, 109 with cancer but not high risk, and 36 with high risk cancer) [6]. High risk cancer was defined as death from prostate cancer, PSA level of >=20ng/ml at diagnosis, or Gleason score of >=8. This study questioned many of the previous studies that are done in men with baseline hormonal dysfunction (i.e. hypogonadal men) that might not be representative of the general population, and prevent the formation of universal guidelines or understanding of the disease process. However, the men who developed high-risk prostate cancer were of 7.7 years older at presentation than the remainder (p<0.001). Leibowitz RL et al reviewed records of 96 patients who received high dose T therapy after initial management for prostate cancer [13]. Mean age at diagnosis was 61 (46-85), 60% having PSA <10 ng/ml, 77% having stage T1c-T2 at diagnosis, 72 patients with Gleason score <=7; and median PSA level before TRT 0.1 ng/ml. The retrospective results from 7 years are: 41 men has PSA progression while on TRT, 7 had radiological progression of disease, 56 men discontinued TRT due to increasing PSA levels and 59% of these men had significant reductions in PSA level with no additional intervention; 31 men remained on TRT with no PSA or radiological progression at a median of 36.7 months. In this study nearly 40% patients had no PSA elevations while on T therapy, 60% had increasing PSA and that triggered discontinuation of TRT. In most of patients TRT was not associated with clinical or symptomatic disease progression. DISCUSSION: There is no dispute that androgens have an important role in the development and growth of prostate tissue. The mechanism of action of androgen on prostate tissue has been recently reviewed [14]. Briefly, T enters the prostate cell where it is largely metabolized in the cytoplasm to DHT (Dihydrotestosterone) by the enzyme 5 alpha-reductase [15]. DHT is the primary intraprostatic androgen, as it binds more avidly than T to the Androgen Receptor (AR), which in turn is responsible for mediating androgenic action on the prostate cell. Once bound, the androgen-AR complex translocates to the cell nucleus where it is able to bind directly to DNA, thus exerting its proliferative and trophic effects.
Whether to use T therapy in men with PCa or not is a dilemma for past decades. There is no standardized protocol that a clinician should follow when faced with a symptomatic hypogonadal man with history of prostate cancer. The growing impetus
for reconsidering T therapy stems from many factors, one of which is the increasing recognition of the health benefits of T Therapy in hypogonadal men; including improvements in energy, vitality, sexual desire, erectile function, body composition and bone mineral density [7]. Prostate growth is exquisitely sensitive to variations in androgen concentrations at or below the near–castrate range, but becomes insensitive to changes in androgen concentrations at higher levels [2]. Pierorazio PM et al [6] noted that high or even normal values of serum testosterone might be related to development of high-risk prostate cancer in older men. The authors explained that for younger men androgens might be protective by promoting typical growth and maturation of the prostate, while for older men in whom malignant transformation has occurred, androgens might be harmful by promoting disease progression.
Therefore we are still struggling to answer these questions: Is it reasonable to offer T therapy when some studies showed substantial risk of PCa growth in particular age group [6]. On the other hand, is it ethical to deny a beneficial therapy to hypogonadal patients with PCa when the risk is theoretical and high dose T therapy has not shown progression of disease [2,5].
The decision to start T replacement therapy is also influenced by age of the patient, PSA and serum testosterone levels at start of therapy, stage of PCa at diagnosis, Gleason score, hormonally intactness status, severity of hypogonadal symptoms and feasibility for rigorous surveillance.
CONCLUSION: Testosterone Replacement therapy is beneficial for patients having clinical symptoms of hypogonadism and treatment needs to be individualized focusing on each patient’s benefits and risk. The patient should be explained all the risks of this therapy at the time of consent and needs to be followed with active surveillance of prostate markers. Anytime patient presents with unfavorable symptoms should be considered seriously and a call for withdrawal of therapy is likely warranted. It is also important to recognize the androgen status of each study population, and that high or low serum androgens might have distinct implications in different subpopulations of men (i.e. the hypogonadal vs the eugonadal) at risk of prostate cancer [6].
Again much research needs to be done in this area to enhance our understanding of disease and treatment strategies.
REFERENCES :
1. Huggins C , Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection
on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol. 2002 Jul;168(1):9-12.
2. Eur Urol. 2009 Jul; 56(1):e4; author reply e5. Epub 2009 Apr 1. Re: Abraham Morgentaler, Abdulmaged M. Traish.
Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgendependent
growth. Eur Urol 2009; 55:310-21. PMID: 19349108
3. Sakr WA , Grignon DJ, Crissman JD,et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic
adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo. 1994 May-Jun; 8(3):439-43.
PMID: 7803731
4. Fowler JE Jr , Whitmore WF Jr. The response of metastatic adenocarcinoma of the prostate to exogenous testosterone.
J Urol. 1981 Sep; 126(3):372-5. PMID: 7277602
5. Morgentaler A . Two years of testosterone therapy associated with decline in prostate-specific antigen in a man with
untreated prostate cancer. J Sex Med. 2009 Feb; 6(2):574-7.
6. Pierorazio PM , Ferrucci L, Kettermann A, Longo DL, Metter EJ, Carter HB. Serum testosterone is associated with
aggressive prostate cancer in older men: results from the Baltimore Longitudinal Study of Aging. BJU Int. 2010 Mar;
105(6):884-5; author reply 885-6. PMID: 19751256
7. Wang C , Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS.
Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and
fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 2004 May; 89(5):2085-98. PMID:
15126525
8. Monath JR , McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum testosterone within the normal range do
not affect serum prostate-specific antigen. Urology. 1995 Jul; 46(1):58-61. PMID: 7541587
9. Mohr BA , Feldman HA, Kalish LA, Longcope C, McKinlay JB. Are serum hormones associated with the risk of prostate
cancer? Prospective results from the Massachusetts Male Aging Study. Urology. 2001 May; 57(5):930-5.
10. Bhasin S , Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R. The
effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996 Jul
4; 335(1):1-7.
11. Agarwal PK , Oefelein MG. Testosterone replacement therapy after primary treatment for prostate cancer. J Urol. 2005
Feb; 173(2):533-6.
12. Kaufman JM , Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in
hypogonadal men. J Urol. 2004 Sep; 172(3):920-2.
13. Leibowitz RL , Dorff TB, Tucker S, Symanowski J, Vogelzang NJ Testosterone replacement in prostate cancer survivors
with hypogonadal symptoms. BJU Int. 2010 May; 105(10):1397-401. Epub 2009 Nov 11.
14. Tindall DJ , Rittmaster RS. The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of
prostate cancer. J Urol. 2008 Apr; 179(4):1235-42. Epub 2008 Feb 20. Mayo Clinic, Rochester, Minnesota 55905, USA.
tindall@mayo.edu
15. Morgentaler A . Testosterone therapy in men with prostate cancer: scientific and ethical considerations. J Urol. 2009
Mar; 181(3):972-9. Epub 2009 Jan 16.
Thursday, February 3, 2011
Emotional factor is linked to Anorgasmia !
Can anorgasmia be linked to emotional dissatisfaction in relationships?
J. Jhaveri, S. Ghannam, N. Kalantarova, J. Randhawa, J. Kashanian, J. LaJeune, Ridwan Shabsigh
journal of men's health
October 2010 (Vol. 7, Issue 3, Page 337)
Anorgasmia is a type of sexual dysfunction in which a person cannot achieve orgasm, even with adequate stimulation.
J. Jhaveri, S. Ghannam, N. Kalantarova, J. Randhawa, J. Kashanian, J. LaJeune, Ridwan Shabsigh
journal of men's health
October 2010 (Vol. 7, Issue 3, Page 337)
Anorgasmia is a type of sexual dysfunction in which a person cannot achieve orgasm, even with adequate stimulation.
Thursday, January 20, 2011
Specific drug treatment for Amyotropic Lateral Sclerosis ( ALS ) patients!
Riluzole has been found to increase survival in few studies and is now (as of 2010-11) being used for ALS patients.
Anti-retroviral drugs ( Class NNRTI )
Why HIV patients get many drugs combined for their treatment?
Anti retroviral drugs are given in combination therapy to overcome the viral resistance development.
e.g. NRTIs, NNRTIs, Protease Inhibitors etc.
Class NNTRI drugs include:
1. Nevirapine
2. Efavirenz
3. Delavirdine
Nevirapine: - ( the first drug approved by FDA in US ) Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA.
Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs bind allosterically at a distinct site away from the active site termed the NNRTI pocket. Nevirapine also has very good central neverous system (CNS) penetration.
Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.
As all NNRTIs bind within the same pocket, viral strains which are resistant to nevirapine are usually also resistant to the other NNRTIs, efavirenz and delavirdine.
Anti retroviral drugs are given in combination therapy to overcome the viral resistance development.
e.g. NRTIs, NNRTIs, Protease Inhibitors etc.
Class NNTRI drugs include:
1. Nevirapine
2. Efavirenz
3. Delavirdine
Nevirapine: - ( the first drug approved by FDA in US ) Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA.
Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs bind allosterically at a distinct site away from the active site termed the NNRTI pocket. Nevirapine also has very good central neverous system (CNS) penetration.
Nevirapine is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.
As all NNRTIs bind within the same pocket, viral strains which are resistant to nevirapine are usually also resistant to the other NNRTIs, efavirenz and delavirdine.
Subscribe to:
Posts (Atom)