rakesh sharma - Academia.edu (original) (raw)
Papers by rakesh sharma
Now a days as one of the most important renewable source of energy is wind energy that is gaining... more Now a days as one of the most important renewable source of energy is wind energy that is gaining interest due to its ecofriendly nature. This paper is about the study on control of wind driven doubly fed induction generator. A converter setup that is back to back PWM with stator voltage oriented vector control is used to control the DFIG. The back to back PWM converter set up consists of the Rotor Side Converter and the Grid Side Converter with intermediate DC link. Decoupled control of the DC link voltage and the grid reactive power is obtained through Voltage oriented control of GSC. Similarly independent control of power from wind and reactive power of DFIG is carried out by stator voltage oriented vector control of RSC. Coordinated control of the back to back converter setup in both sub synchronous and super synchronous mode is presented.
— The wind power is a pollution free source of energy. In this paper we have focused on analyzing... more — The wind power is a pollution free source of energy. In this paper we have focused on analyzing the performance of wind power in conventional system under various scenarios. Here we have introduced a wind power in a power generation and transmission system alongside the conventional 3-phase sources and have simulated its working and performance. The wind power is made to work in tandem with the regular supply. In case of faults occurring in the system wind power is used to act as backup for the original supply. Also in case of extra power demand in peak time periods, it has been used to complement the power sources there by maintaining the power quality and frequency in the system. To analysis the performance of DFIG wind system during three phase fault there is two cases (i) Performance analysis of DFIG during fault at fixed wind speed (ii) Performance analysis of DFIG during fault at variable wind speed. All these scenarios have been simulated with the help of the simulation program using MATLAB and its inbuilt components provided in SIMULINK library.
The wind energy sources are characterized by irregularity and unpredictability. It is very import... more The wind energy sources are characterized by irregularity and unpredictability. It is very important to make DC-link voltage constant for doubly fed induction generator wind energy conversion system. The DC-link provides an extra spinning reserve facility for the wind system, which can be used for sink or source of active power. This paper presents the DC-link voltage fluctuation for a back to back pulse width modulation converter in doubly fed induction generator for wind turbine systems. The effects of load variation on DC link electrolytic capacitor voltage of DFIG based wind energy conversion system (WECS).As DFIG based WECS utilize low power converter, so there is a need to explore the effects of DC-link voltage. For this there are two cases (i) At fixed speed effect of load variation on dc link voltage V dc (ii) At variable speed effect of load variation on dc link voltage V dc . These cases are compared with healthy fixed and variable DFIG wind energy conversion system. All these scenarios have been simulated with the help of the simulation program using MATLAB and its inbuilt components provided in SIMULINK library. .
Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemo... more Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results-For the derivation study, 112 patients with CHF (age 59Ϯ12 years, peak oxygen consumption [V O 2 ] 17Ϯ7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (nϭ182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (nϭ120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 mol/L (9.50 mg/dL) (independently of age, peak V O 2 , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; PϽ0.0001). In the validation study, UA Ն565 mol/L predicted mortality (hazard ratio, 7.14; PϽ0.0001). In 16 patients (from both studies) with UA Ն565 mol/L, left ventricular ejection fraction Յ25% and peak V O 2 Յ14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, PϽ0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions-High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.
Journal of The American College of Cardiology, 2003
We sought to describe the relationship between cholesterol and survival in patients with chronic ... more We sought to describe the relationship between cholesterol and survival in patients with chronic heart failure (CHF). BACKGROUND Increasing lipoprotein levels are a cardiovascular risk factor. In patients with CHF, the prognostic value of endogenous lipoproteins is not fully clarified.
Background-Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessm... more Background-Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously. Methods and Results-We studied 86 patients with PPH (58 female, age 46Ϯ2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60Ϯ2 mm Hg, average pulmonary vascular resistance was 1664Ϯ81 dyne · s · cm Ϫ5 , average serum uric acid level was 7.5Ϯ0.35 mg/dL, and average peak oxygen uptake during exercise (peak V O 2 ) was 11.2Ϯ0.5 mL · kg Ϫ1 · min Ϫ1 . During follow-up (mean: 567Ϯ48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak V O 2 (PϽ0.0001) and low systolic blood pressure at peak exercise (peak SBP; PϽ0.0001). In a multivariable analysis, serum uric acid levels (all PϽ0.005) and diastolic blood pressure at peak exercise independently predicted survival (PϽ0.05). Patients with peak V O 2 Յ10.4 mL · kg Ϫ1 · min Ϫ1 and peak SBP Յ120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively). Conclusions-Peak V O 2 and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information. (Circulation. 2002;106:319-324.)
Objective: To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of... more Objective: To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of infertile men with a history of cigarette smoking. Design: A prospective clinical study. Setting: Male infertility clinic, Urological Institute, the Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Infertile men who smoked cigarettes (n ϭ 20), infertile men who were nonsmokers (n ϭ 32), and healthy nonsmoking donors (n ϭ 13). Intervention(s): Genital examination, standard semen analysis, sperm DNA damage. Main Outcome Measure(s): Levels of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) measured by a chemiluminescence assay and seminal OS assessed by calculating a ROS-TAC score. Sperm DNA damage was measured by sperm chromatin structure assay.
Fertility and Sterility, 2000
To determine whether particular semen characteristics in various clinical diagnoses of infertilit... more To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. Design: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. Setting: Male infertility clinic of a tertiary care center. Patient(s): One hundred sixty-seven infertile patients and 19 controls. Intervention(s): None. Main Outcome Measure(s): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. Result(s): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P ϭ .02), except in varicocele associated with infection group. Mean (ϮSD) ROS levels in patient groups ranged from 2.2 Ϯ 0.13 to 3.2 Ϯ 0.35, significantly higher than controls (1.3 Ϯ 0.3; PϽ.005). Patient groups had a significantly lower mean (ϮSD) TAC from 1014.75 Ϯ 79.22 to 1173.05 Ϯ 58.07 than controls (1653 Ϯ 115.28, PϽ.001), except in the vasectomy reversal group (1532.02 Ϯ 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (PՅ.007), with the exception of idiopathic infertility. Conclusion(s): Irrespective of the clinical diagnosis and semen characteristics, the presence of seminal oxidative stress in infertile men suggests its role in the pathophysiology of infertility. Medical or surgical treatments for infertility in these men should include strategies to reduce oxidative stress. (Fertil Steril 2000; 73:459 -64.
Fertility and Sterility, 2003
Objective: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with ... more Objective: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with varicocele. Design: Prospective controlled study. Setting: Male infertility clinic, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Thirty-one infertility patients and 16 fertile controls. Intervention(s): Sperm DNA fragmentation index (DFI), levels of seminal reactive oxygen species (ROS), and total antioxidant capacity (TAC) were assessed using the sperm chromatin structure assay, chemiluminescence assay, and enhanced chemiluminescence assay, respectively. ROS-TAC score was calculated as a measure of OS. Main Outcome Measure(s): Median (interquartile range) DFI and ROS-TAC scores. Result(s): Sixteen of the 31 patients had left varicocele [grade I (n ϭ 3), grade II (n ϭ 10), and grade III (n ϭ ], and the remaining 15 had normal genital examination. Patients with varicoceles had significantly higher percent DFI than controls (25%, range: 20%-35%; vs. 15%, range: 10%-22%). Patients with varicoceles had significantly lower ROS-TAC scores (21, range: 9.5-31) than the infertile patients with normal genital examination (34, range: 28 -42) or the controls (40.3, range: 38 -44).
Fertility and Sterility, 1997
BACKGROUND: The aim of this study was to examine the role of apoptosis and reactive oxygen specie... more BACKGROUND: The aim of this study was to examine the role of apoptosis and reactive oxygen species (ROS) in inducing DNA damage in ejaculated spermatozoa. METHODS: We examined ejaculated spermatozoa from 31 patients examined for infertility and 19 healthy donors for apoptosis, production of ROS and DNA damage using annexin V binding, chemiluminescence assay and sperm chromatin structure assay. RESULTS: The percentage of spermatozoa that underwent apoptosis in the whole ejaculate and mature fraction was higher in the patients than in the donors (P < 0.001 and P = 0.009, respectively). Levels of ROS in the whole ejaculate and immature fraction were higher in the patients than in the donors (P = 0.002 and P = 0.009). Apoptosis was signi®cantly correlated with ROS within patients in the whole ejaculate [r (95% con®dence interval) = 0.53 (0.19±0.86)] and in the mature [0.71 (0.39± 1.00)] and immature spermatozoa [0.75 (0.45±1.00)]. Only apoptosis and the DNA fragmentation index (DFI) were signi®cantly correlated within patients in the whole ejaculate [0.57 (0.18±0.97)]. CONCLUSIONS: DNA damage may be induced by oxidative assault. Apoptosis may not contribute signi®cantly to the DNA damage.
Journal of Urology, 1999
Purpose: Because varicocele is seen often in infertile men and oxidative stress has been implicat... more Purpose: Because varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele. Materials and Methods: Levels of reactive oxygen species and total antioxidant capacity were measured in the semen of 21 infertile men with varicocele, 15 men with incidential varicocele and 17 normal donors without varicocele (controls). Men with leukocytospermia (more than 1x10 6 white blood cells per ml.) were excluded from study. Reactive oxygen species were measured in washed spermatozoa with a luminol dependent chemiluminescence assay. Total seminal antioxidant capacity was measured with an enhanced chemiluminescence assay, and the results were expressed as trolox equivalents. Sperm characteristics were assessed with a computer assisted semen analyzer, and sperm morphology was assessed using World Health Organization and Kruger's strict criteria. Results: Patients with varicocele had significantly higher reactive oxygen species levels than controls (p = 0.02). Reactive oxygen species levels did not differ significantly between infertile and men with incidental varicocele. Total antioxidant levels were significantly lower among men with varicocele (p = 0.02) and those with incidental varicocele compared to controls (p = 0.05). Reactive oxygen species and total antioxidant capacity levels did not correlate in any group. Conclusions: Our results suggest that elevated reactive oxygen species and depressed total antioxidant capacity levels are associated with varicocele. These changes may be related to functional sperm abnormalities and infertility seen commonly in these patients. These findings support a possible rationale for controlled clinical trials of antioxidant supplementation in infertile men with varicocele.
The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TA... more The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean ± SE, 3.25 ± 0.89) and vasectomy reversals (2.65 ± 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 ± 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 ± 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminat¬ ing between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.
Fertility and Sterility, 1997
A total of 28 donor semen samples were used to evaluate the characteristics of laboratory variabi... more A total of 28 donor semen samples were used to evaluate the characteristics of laboratory variability in measuring reactive oxygen species (ROS). The objectives of this study were to assess the interassay (same sample observed on different days by the same observers) variability; interdonor, intraobserver (replications of the same sample on the same day) variability; and interobserver (multiple observers on the same day with the same sample) variability of the luminol-dependent chemiluminescence assay and to establish an optimal semen age and sperm concentration. Semen samples were collected from 6 healthy donors for 108 measures of ROS. ROS levels were measured by the assay using luminol as the probe. An additional assessment measured the effect of time (age of the sample) on ROS production in 12 donor samples at 60, 120, 180, and 240 minutes after the specimen was produced. Last, to evaluate the effect of sperm concentration on ROS production, ROS levels were measured in 10 donor sample aliquots with sperm concentrations ranging from 1 to 120 ϫ 10 6 /mL. In the controls, the mean ROS level was 0.218 ϫ 10 6 counted photons per minute; the interassay variability standard deviation (SD) was 0.077. The inter-observer SD was 0.002 for an interobserver reliability of 97.5% (coefficient of variation [CV] ϭ 0.9%). The intraobserver (between replication) SD was 0.001 for an intraobserver reliability of 98.7% (CV ϭ 0.5%). The interassay SD was 0.005 for an interassay reliability of 93.8% (CV ϭ 2.0%). There was no statistically significant interobserver, intraobserver, or interassay variation (P Ͼ .80). ROS levels decreased significantly with time; a dramatic decline in ROS production was seen in the specimens that were more than 60 minutes old (P Ͻ .001). ROS values decreased by 31% at 120 minutes and 62% at 180 minutes compared with the 60-minute-old specimens. A linear relationship was seen between the ROS levels and sperm concentration in 8 of the 10 samples analyzed (R 2 ϭ .99). Our results demonstrate that the luminol-dependent chemiluminescence assay for ROS measurement is both accurate and reliable when the sperm concentration is greater than 1 ϫ 10 6 /mL and the samples are analyzed within the first hour after specimen collection.
Fertility and Sterility, 2002
Objective: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnorm... more Objective: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnormal standard semen parameters. Design: Prospective study. Setting: Male infertility clinic. Patient(s): Ninety-two men seeking infertility treatment and 16 fertile volunteers. Intervention(s): Standard semen analysis was performed according to the World Health Organization guidelines. Main Outcome Measure(s): Sperm DNA damage was assessed by sperm chromatin structure assay and the results expressed as %DFI. Result(s): Of the 92 patients, 21 (23%) had normal standard sperm parameters (concentration, motility, and normal sperm forms), while 71 (77%) had an abnormality in one or more of these parameters. The %DFI [median (25th and 75th percentiles)] in infertile men with normal sperm parameters [23 (15, 32)] was significantly higher than fertile donors [15 (11, 20)] (Pϭ.02), but not significantly different from infertile men with abnormal sperm parameters [28 (18, 41)] (Pϭ.27).
BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in hum... more BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. METHODS: Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. RESULTS: DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. CONCLUSIONS: The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.
Urology, 2000
Objectives. An association between prostatitis and male infertility has been suspected, yet is po... more Objectives. An association between prostatitis and male infertility has been suspected, yet is poorly understood. Prostatitis is often associated with granulocytes in the prostatic fluid that generate reactive oxygen species (ROS), known to impair male fertility. We compared ROS, the total antioxidant capacity (TAC), and a novel index of oxidative stress (ROS-TAC score) in patients with chronic prostatitis and in healthy controls. Methods. Semen specimens from 36 men with chronic prostatitis (National Institutes of Health category IIIa), 8 men with prostatodynia (National Institutes of Health category IIIb), and 19 controls attending our urologic clinic were examined according to the World Health Organization criteria. Leukocytospermia was measured by the Endtz test (myeloperoxidase assay). ROS and TAC production was measured by chemiluminescence assay. A composite ROS-TAC score was also calculated in patients and controls. Results. The sperm concentration, percentage of motility, and morphology among the groups did not differ. The mean ± standard error log-transformed ROS level was significantly higher in patients with leukocytospermia (3.2 ± 0.6) than in patients without leukocytospermia (1.8 ± 0.2; P = 0.04) and controls (1.3 ± 0.3, P = 0.01). TAC was significantly lower in patients with or without leukocytospermia (859.69 ± 193.0 and 914.9 ± 65.2, respectively) than in controls (1653.98 ± 93.6, P = 0.001). The mean ROS-TAC score of controls (50.0 ± 4.1) was significantly higher than those of patients with chronic prostatitis and leukocytospermia (8.2 ± 9.2) and those without leukocytospermia (34.2 ± 2.9; P <0.001). Conclusions. Men with chronic prostatitis or prostatodynia have seminal oxidative stress, irrespective of their leukocytospermia status. These observations may help shed light on the long-standing controversy surrounding prostatitis and infertility. UROLOGY 55: 881-885, 2000. © 2000, Elsevier Science Inc.
Fertility and Sterility, 2003
To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in m... more To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Design: Prospective study. Setting: Infertility clinic at a tertiary care academic institution. Patient(s): Ninety-two infertile men with normal female partners. Sixteen fertile donors served as the control group. Intervention(s): Standard semen analysis and assessment of levels of seminal oxidative stress. Assisted reproductive techniques in 33 of the 92 patients (IUI [n ϭ 19], IVF [n ϭ 10], and intracytoplasmic sperm injection [n ϭ 4]). Main Outcome Measure(s): Sperm DNA damage by sperm chromatin structure assay. Results were expressed as DNA fragmentation index. Result(s): Patients were classified as having either idiopathic (n ϭ 23) or male factor infertility (n ϭ 69).
Now a days as one of the most important renewable source of energy is wind energy that is gaining... more Now a days as one of the most important renewable source of energy is wind energy that is gaining interest due to its ecofriendly nature. This paper is about the study on control of wind driven doubly fed induction generator. A converter setup that is back to back PWM with stator voltage oriented vector control is used to control the DFIG. The back to back PWM converter set up consists of the Rotor Side Converter and the Grid Side Converter with intermediate DC link. Decoupled control of the DC link voltage and the grid reactive power is obtained through Voltage oriented control of GSC. Similarly independent control of power from wind and reactive power of DFIG is carried out by stator voltage oriented vector control of RSC. Coordinated control of the back to back converter setup in both sub synchronous and super synchronous mode is presented.
— The wind power is a pollution free source of energy. In this paper we have focused on analyzing... more — The wind power is a pollution free source of energy. In this paper we have focused on analyzing the performance of wind power in conventional system under various scenarios. Here we have introduced a wind power in a power generation and transmission system alongside the conventional 3-phase sources and have simulated its working and performance. The wind power is made to work in tandem with the regular supply. In case of faults occurring in the system wind power is used to act as backup for the original supply. Also in case of extra power demand in peak time periods, it has been used to complement the power sources there by maintaining the power quality and frequency in the system. To analysis the performance of DFIG wind system during three phase fault there is two cases (i) Performance analysis of DFIG during fault at fixed wind speed (ii) Performance analysis of DFIG during fault at variable wind speed. All these scenarios have been simulated with the help of the simulation program using MATLAB and its inbuilt components provided in SIMULINK library.
The wind energy sources are characterized by irregularity and unpredictability. It is very import... more The wind energy sources are characterized by irregularity and unpredictability. It is very important to make DC-link voltage constant for doubly fed induction generator wind energy conversion system. The DC-link provides an extra spinning reserve facility for the wind system, which can be used for sink or source of active power. This paper presents the DC-link voltage fluctuation for a back to back pulse width modulation converter in doubly fed induction generator for wind turbine systems. The effects of load variation on DC link electrolytic capacitor voltage of DFIG based wind energy conversion system (WECS).As DFIG based WECS utilize low power converter, so there is a need to explore the effects of DC-link voltage. For this there are two cases (i) At fixed speed effect of load variation on dc link voltage V dc (ii) At variable speed effect of load variation on dc link voltage V dc . These cases are compared with healthy fixed and variable DFIG wind energy conversion system. All these scenarios have been simulated with the help of the simulation program using MATLAB and its inbuilt components provided in SIMULINK library. .
Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemo... more Background-Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF). Methods and Results-For the derivation study, 112 patients with CHF (age 59Ϯ12 years, peak oxygen consumption [V O 2 ] 17Ϯ7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (nϭ182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (nϭ120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 mol/L (9.50 mg/dL) (independently of age, peak V O 2 , left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; PϽ0.0001). In the validation study, UA Ն565 mol/L predicted mortality (hazard ratio, 7.14; PϽ0.0001). In 16 patients (from both studies) with UA Ն565 mol/L, left ventricular ejection fraction Յ25% and peak V O 2 Յ14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, PϽ0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%. Conclusions-High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.
Journal of The American College of Cardiology, 2003
We sought to describe the relationship between cholesterol and survival in patients with chronic ... more We sought to describe the relationship between cholesterol and survival in patients with chronic heart failure (CHF). BACKGROUND Increasing lipoprotein levels are a cardiovascular risk factor. In patients with CHF, the prognostic value of endogenous lipoproteins is not fully clarified.
Background-Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessm... more Background-Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously. Methods and Results-We studied 86 patients with PPH (58 female, age 46Ϯ2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60Ϯ2 mm Hg, average pulmonary vascular resistance was 1664Ϯ81 dyne · s · cm Ϫ5 , average serum uric acid level was 7.5Ϯ0.35 mg/dL, and average peak oxygen uptake during exercise (peak V O 2 ) was 11.2Ϯ0.5 mL · kg Ϫ1 · min Ϫ1 . During follow-up (mean: 567Ϯ48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak V O 2 (PϽ0.0001) and low systolic blood pressure at peak exercise (peak SBP; PϽ0.0001). In a multivariable analysis, serum uric acid levels (all PϽ0.005) and diastolic blood pressure at peak exercise independently predicted survival (PϽ0.05). Patients with peak V O 2 Յ10.4 mL · kg Ϫ1 · min Ϫ1 and peak SBP Յ120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively). Conclusions-Peak V O 2 and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information. (Circulation. 2002;106:319-324.)
Objective: To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of... more Objective: To investigate levels of seminal oxidative stress (OS) and sperm quality in a group of infertile men with a history of cigarette smoking. Design: A prospective clinical study. Setting: Male infertility clinic, Urological Institute, the Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Infertile men who smoked cigarettes (n ϭ 20), infertile men who were nonsmokers (n ϭ 32), and healthy nonsmoking donors (n ϭ 13). Intervention(s): Genital examination, standard semen analysis, sperm DNA damage. Main Outcome Measure(s): Levels of seminal reactive oxygen species (ROS) and total antioxidant capacity (TAC) measured by a chemiluminescence assay and seminal OS assessed by calculating a ROS-TAC score. Sperm DNA damage was measured by sperm chromatin structure assay.
Fertility and Sterility, 2000
To determine whether particular semen characteristics in various clinical diagnoses of infertilit... more To determine whether particular semen characteristics in various clinical diagnoses of infertility are associated with high oxidative stress and whether any group of infertile men is more likely to have high seminal oxidative stress. Reactive oxygen species (ROS) play an important role in sperm physiological functions, but elevated levels of ROS or oxidative stress are related to male infertility. Design: Measurement of sperm concentration, motility, morphology, seminal ROS, and total antioxidant capacity (TAC) in patients seeking infertility treatment and controls. Setting: Male infertility clinic of a tertiary care center. Patient(s): One hundred sixty-seven infertile patients and 19 controls. Intervention(s): None. Main Outcome Measure(s): Semen characteristics, seminal ROS, and TAC in samples from patients with various clinical diagnoses and controls. Result(s): Fifteen patients (9.0%) were Endtz positive and 152 (91.0%) Endtz negative. Sperm concentration, motility, and morphology were significantly reduced in all groups compared with the controls (P ϭ .02), except in varicocele associated with infection group. Mean (ϮSD) ROS levels in patient groups ranged from 2.2 Ϯ 0.13 to 3.2 Ϯ 0.35, significantly higher than controls (1.3 Ϯ 0.3; PϽ.005). Patient groups had a significantly lower mean (ϮSD) TAC from 1014.75 Ϯ 79.22 to 1173.05 Ϯ 58.07 than controls (1653 Ϯ 115.28, PϽ.001), except in the vasectomy reversal group (1532.02 Ϯ 74.24). Sperm concentration was negatively correlated with ROS both overall and within all groups (PՅ.007), with the exception of idiopathic infertility. Conclusion(s): Irrespective of the clinical diagnosis and semen characteristics, the presence of seminal oxidative stress in infertile men suggests its role in the pathophysiology of infertility. Medical or surgical treatments for infertility in these men should include strategies to reduce oxidative stress. (Fertil Steril 2000; 73:459 -64.
Fertility and Sterility, 2003
Objective: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with ... more Objective: To examine levels of sperm DNA damage and oxidative stress (OS) in infertile men with varicocele. Design: Prospective controlled study. Setting: Male infertility clinic, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Thirty-one infertility patients and 16 fertile controls. Intervention(s): Sperm DNA fragmentation index (DFI), levels of seminal reactive oxygen species (ROS), and total antioxidant capacity (TAC) were assessed using the sperm chromatin structure assay, chemiluminescence assay, and enhanced chemiluminescence assay, respectively. ROS-TAC score was calculated as a measure of OS. Main Outcome Measure(s): Median (interquartile range) DFI and ROS-TAC scores. Result(s): Sixteen of the 31 patients had left varicocele [grade I (n ϭ 3), grade II (n ϭ 10), and grade III (n ϭ ], and the remaining 15 had normal genital examination. Patients with varicoceles had significantly higher percent DFI than controls (25%, range: 20%-35%; vs. 15%, range: 10%-22%). Patients with varicoceles had significantly lower ROS-TAC scores (21, range: 9.5-31) than the infertile patients with normal genital examination (34, range: 28 -42) or the controls (40.3, range: 38 -44).
Fertility and Sterility, 1997
BACKGROUND: The aim of this study was to examine the role of apoptosis and reactive oxygen specie... more BACKGROUND: The aim of this study was to examine the role of apoptosis and reactive oxygen species (ROS) in inducing DNA damage in ejaculated spermatozoa. METHODS: We examined ejaculated spermatozoa from 31 patients examined for infertility and 19 healthy donors for apoptosis, production of ROS and DNA damage using annexin V binding, chemiluminescence assay and sperm chromatin structure assay. RESULTS: The percentage of spermatozoa that underwent apoptosis in the whole ejaculate and mature fraction was higher in the patients than in the donors (P < 0.001 and P = 0.009, respectively). Levels of ROS in the whole ejaculate and immature fraction were higher in the patients than in the donors (P = 0.002 and P = 0.009). Apoptosis was signi®cantly correlated with ROS within patients in the whole ejaculate [r (95% con®dence interval) = 0.53 (0.19±0.86)] and in the mature [0.71 (0.39± 1.00)] and immature spermatozoa [0.75 (0.45±1.00)]. Only apoptosis and the DNA fragmentation index (DFI) were signi®cantly correlated within patients in the whole ejaculate [0.57 (0.18±0.97)]. CONCLUSIONS: DNA damage may be induced by oxidative assault. Apoptosis may not contribute signi®cantly to the DNA damage.
Journal of Urology, 1999
Purpose: Because varicocele is seen often in infertile men and oxidative stress has been implicat... more Purpose: Because varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele. Materials and Methods: Levels of reactive oxygen species and total antioxidant capacity were measured in the semen of 21 infertile men with varicocele, 15 men with incidential varicocele and 17 normal donors without varicocele (controls). Men with leukocytospermia (more than 1x10 6 white blood cells per ml.) were excluded from study. Reactive oxygen species were measured in washed spermatozoa with a luminol dependent chemiluminescence assay. Total seminal antioxidant capacity was measured with an enhanced chemiluminescence assay, and the results were expressed as trolox equivalents. Sperm characteristics were assessed with a computer assisted semen analyzer, and sperm morphology was assessed using World Health Organization and Kruger's strict criteria. Results: Patients with varicocele had significantly higher reactive oxygen species levels than controls (p = 0.02). Reactive oxygen species levels did not differ significantly between infertile and men with incidental varicocele. Total antioxidant levels were significantly lower among men with varicocele (p = 0.02) and those with incidental varicocele compared to controls (p = 0.05). Reactive oxygen species and total antioxidant capacity levels did not correlate in any group. Conclusions: Our results suggest that elevated reactive oxygen species and depressed total antioxidant capacity levels are associated with varicocele. These changes may be related to functional sperm abnormalities and infertility seen commonly in these patients. These findings support a possible rationale for controlled clinical trials of antioxidant supplementation in infertile men with varicocele.
The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TA... more The imbalance between reactive oxygen species (ROS) production and total antioxidant capacity (TAC) in seminal fluid indicates oxidative stress and is correlated with male infertility. A composite ROS-TAC score may be more strongly correlated with infertility than ROS or TAC alone. We measured ROS, TAC, and ROS-TAC scores in semen from 127 patients and 24 healthy controls. Of the patients, 56 had varicocele, eight had varicocele with prostatitis, 35 had vasectomy reversals, and 28 had idiopathic infertility. ROS levels were higher among infertile men, especially those with varicocele with prostatitis (mean ± SE, 3.25 ± 0.89) and vasectomy reversals (2.65 ± 1.01). All infertile groups had significantly lower ROS-TAC scores than control. ROS-TAC score identified 80% of patients and was significantly better than ROS at identifying varicocele and idiopathic infertility. The 13 patients whose partners later achieved pregnancies had a mean ROS-TAC score of 47.7 ± 13.2, similar to controls but significantly higher than the 39 patients who remained infertile (35.8 ± 15.0; P < 0.01). ROS-TAC score is a novel measure of oxidative stress and is superior to ROS or TAC alone in discriminat¬ ing between fertile and infertile men. Infertile men with male factor or idiopathic diagnoses had significantly lower ROS-TAC scores than controls, and men with male factor diagnoses that eventually were able to initiate a successful pregnancy had significantly higher ROS-TAC scores than those who failed.
Fertility and Sterility, 1997
A total of 28 donor semen samples were used to evaluate the characteristics of laboratory variabi... more A total of 28 donor semen samples were used to evaluate the characteristics of laboratory variability in measuring reactive oxygen species (ROS). The objectives of this study were to assess the interassay (same sample observed on different days by the same observers) variability; interdonor, intraobserver (replications of the same sample on the same day) variability; and interobserver (multiple observers on the same day with the same sample) variability of the luminol-dependent chemiluminescence assay and to establish an optimal semen age and sperm concentration. Semen samples were collected from 6 healthy donors for 108 measures of ROS. ROS levels were measured by the assay using luminol as the probe. An additional assessment measured the effect of time (age of the sample) on ROS production in 12 donor samples at 60, 120, 180, and 240 minutes after the specimen was produced. Last, to evaluate the effect of sperm concentration on ROS production, ROS levels were measured in 10 donor sample aliquots with sperm concentrations ranging from 1 to 120 ϫ 10 6 /mL. In the controls, the mean ROS level was 0.218 ϫ 10 6 counted photons per minute; the interassay variability standard deviation (SD) was 0.077. The inter-observer SD was 0.002 for an interobserver reliability of 97.5% (coefficient of variation [CV] ϭ 0.9%). The intraobserver (between replication) SD was 0.001 for an intraobserver reliability of 98.7% (CV ϭ 0.5%). The interassay SD was 0.005 for an interassay reliability of 93.8% (CV ϭ 2.0%). There was no statistically significant interobserver, intraobserver, or interassay variation (P Ͼ .80). ROS levels decreased significantly with time; a dramatic decline in ROS production was seen in the specimens that were more than 60 minutes old (P Ͻ .001). ROS values decreased by 31% at 120 minutes and 62% at 180 minutes compared with the 60-minute-old specimens. A linear relationship was seen between the ROS levels and sperm concentration in 8 of the 10 samples analyzed (R 2 ϭ .99). Our results demonstrate that the luminol-dependent chemiluminescence assay for ROS measurement is both accurate and reliable when the sperm concentration is greater than 1 ϫ 10 6 /mL and the samples are analyzed within the first hour after specimen collection.
Fertility and Sterility, 2002
Objective: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnorm... more Objective: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnormal standard semen parameters. Design: Prospective study. Setting: Male infertility clinic. Patient(s): Ninety-two men seeking infertility treatment and 16 fertile volunteers. Intervention(s): Standard semen analysis was performed according to the World Health Organization guidelines. Main Outcome Measure(s): Sperm DNA damage was assessed by sperm chromatin structure assay and the results expressed as %DFI. Result(s): Of the 92 patients, 21 (23%) had normal standard sperm parameters (concentration, motility, and normal sperm forms), while 71 (77%) had an abnormality in one or more of these parameters. The %DFI [median (25th and 75th percentiles)] in infertile men with normal sperm parameters [23 (15, 32)] was significantly higher than fertile donors [15 (11, 20)] (Pϭ.02), but not significantly different from infertile men with abnormal sperm parameters [28 (18, 41)] (Pϭ.27).
BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in hum... more BACKGROUND: Reactive oxygen species (ROS)-induced damage of membrane phospholipids and DNA in human spermatozoa has been implicated in the pathogenesis of male infertility. In this study, variations in ROS production, DNA structure (as measured by the sperm chromatin structure assay) and lipid composition, were studied in human spermatozoa at different stages of maturation. METHODS: Sperm subsets were isolated by discontinuous density gradient centrifugation of semen samples obtained from healthy donors and from infertility patients. RESULTS: DNA damage and ROS production were highest in immature spermatozoa with cytoplasmic retention and abnormal head morphology, and lowest in mature spermatozoa. Docosahexaenoic acid and sterol content were highest in immature germ cells and immature spermatozoa, and lowest in mature spermatozoa. The relative proportion of ROS-producing immature spermatozoa in the sample was directly correlated with DNA damage in mature spermatozoa, and inversely correlated with the recovery of motile spermatozoa. There was no correlation between DNA damage and sperm morphology in mature spermatozoa. CONCLUSIONS: The high levels of ROS production and DNA damage observed in immature spermatozoa may be indicative of derangements in the regulation of spermiogenesis. DNA damage in mature spermatozoa may be the result of oxidative damage by ROS-producing immature spermatozoa during sperm migration from the seminiferous tubules to the epididymis.
Urology, 2000
Objectives. An association between prostatitis and male infertility has been suspected, yet is po... more Objectives. An association between prostatitis and male infertility has been suspected, yet is poorly understood. Prostatitis is often associated with granulocytes in the prostatic fluid that generate reactive oxygen species (ROS), known to impair male fertility. We compared ROS, the total antioxidant capacity (TAC), and a novel index of oxidative stress (ROS-TAC score) in patients with chronic prostatitis and in healthy controls. Methods. Semen specimens from 36 men with chronic prostatitis (National Institutes of Health category IIIa), 8 men with prostatodynia (National Institutes of Health category IIIb), and 19 controls attending our urologic clinic were examined according to the World Health Organization criteria. Leukocytospermia was measured by the Endtz test (myeloperoxidase assay). ROS and TAC production was measured by chemiluminescence assay. A composite ROS-TAC score was also calculated in patients and controls. Results. The sperm concentration, percentage of motility, and morphology among the groups did not differ. The mean ± standard error log-transformed ROS level was significantly higher in patients with leukocytospermia (3.2 ± 0.6) than in patients without leukocytospermia (1.8 ± 0.2; P = 0.04) and controls (1.3 ± 0.3, P = 0.01). TAC was significantly lower in patients with or without leukocytospermia (859.69 ± 193.0 and 914.9 ± 65.2, respectively) than in controls (1653.98 ± 93.6, P = 0.001). The mean ROS-TAC score of controls (50.0 ± 4.1) was significantly higher than those of patients with chronic prostatitis and leukocytospermia (8.2 ± 9.2) and those without leukocytospermia (34.2 ± 2.9; P <0.001). Conclusions. Men with chronic prostatitis or prostatodynia have seminal oxidative stress, irrespective of their leukocytospermia status. These observations may help shed light on the long-standing controversy surrounding prostatitis and infertility. UROLOGY 55: 881-885, 2000. © 2000, Elsevier Science Inc.
Fertility and Sterility, 2003
To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in m... more To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Design: Prospective study. Setting: Infertility clinic at a tertiary care academic institution. Patient(s): Ninety-two infertile men with normal female partners. Sixteen fertile donors served as the control group. Intervention(s): Standard semen analysis and assessment of levels of seminal oxidative stress. Assisted reproductive techniques in 33 of the 92 patients (IUI [n ϭ 19], IVF [n ϭ 10], and intracytoplasmic sperm injection [n ϭ 4]). Main Outcome Measure(s): Sperm DNA damage by sperm chromatin structure assay. Results were expressed as DNA fragmentation index. Result(s): Patients were classified as having either idiopathic (n ϭ 23) or male factor infertility (n ϭ 69).