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A Agarwal

Publications and source records attributed to A Agarwal.

At least 199 records · Page 11Linked to original sources
PubMed1999

Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy.

Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines) identified in our laboratory as potential pharmacophore for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilarical activity was initially evaluated in vivo against Acanthoeilonema viteae. Amongst all the synthesized compounds, only twelve compounds namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i and 7h have exhibited either > 90% micro- or macrofilaricidal activity or sterilization of female worms. These compounds have also been screened against Litomosoides carinii and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure activity relationship (SAR) associated with position-1 and 3 substituents in beta-carbolines have been discussed. It has been observed that the presence of carbomethoxy at position-3 and an aryl substituent at position- in beta-carbolines effectively enhance antifilarial activity particularly against A. viteae. Amongst the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxyla te (3a) has shown highest microfilaricidal action against A. viteae at 50 mg/ kg x 5 days (i.p.). Another derivative of this compound namely 1-(4-chlorophenyl)-3-hydroxymethyl-9H-pyrido[3,4-b]indole (5a) exhibited highest activity against L. carinii at 30 mg/kg x 5 days (i.p.) and against B. malayi at 50 mg/kg x 5 days (i.p.) or at 200 mg/kg x 5 days (p.o.).

Animals↗
PubMed1999

Relationship of total motile sperm count and percentage motile sperm to successful pregnancy rates following intrauterine insemination.

PURPOSE: This study sought (i) to investigate the relationship between postwash total motile sperm count and postwash percentage motile sperm in predicting successful intrauterine insemination and (ii) to determine the minimal postwash total motile sperm count required to achieve pregnancy with intrauterine insemination. METHODS: Five hundred four women, who underwent 1636 intrauterine insemination cycles with their partner's sperm for infertility treatment from 1993 through 1995, were included in this retrospective study. All patient charts were reviewed for age, infertility etiology, ovarian stimulation regimens, semen characteristics, and treatment outcome. To determine the relationship between total motile sperm count and intrauterine insemination outcome, patients were grouped as (1) less than 0.5 million, (2) 0.5 to 1 million, (3) 1 to 5 million, (4) greater than 5 million, and (5) greater than 20 million. RESULTS: Similar live birth rates (per cycle) were seen among the postwash total motile sperm count groups: group 1, 3.5%; group 2, 2.4%; group 3, 7.0%; group 4, 6.9%; and group 5, 7.0% (P = 0.37). However, regardless of the postwash total motile sperm count, the postwash motility predicted intrauterine insemination success at a cutoff value of 40%. CONCLUSIONS: The percentage of postwash sperm motility, and not the postwash total motile sperm count, can predict successful intrauterine insemination outcome. Such information can be useful in counseling patients regarding their chance of success with intrauterine insemination and in determining when alternate methods of assisted reproduction may be a better approach.

Female↗
PubMed1999

Mechanisms of G2 arrest in response to overexpression of p53.

Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was suppressed in response to the induction of p53. Suppression requires the regions -287 to -123 of the cyclin B1 promoter and -104 to -74 of the cdc2 promoter. p53 did not affect the inhibitory phosphorylations of CDC2 at threonine 14 or tyrosine 15 or the activity of the cyclin-dependent kinase that activates CDC2 by phosphorylating it at threonine 161. Overexpression of p53 may also interfere with the accumulation of CDC2/cyclin B1 in the nucleus, required for cells to enter mitosis. Constitutive expression of cyclin B1, alone or in combination with the constitutively active CDC2 protein T14A Y15F, did not reverse p53-dependent G2 arrest. However, targeting cyclin B1 to the nucleus in cells also expressing CDC2 T14A Y15F did overcome this arrest. It is likely that several distinct pathways contribute to p53-dependent G2 arrest.

Apoptosis↗
PubMed1999

The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility.

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 discriminating 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.

Antioxidants↗
PubMed1999

Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat.

PURPOSE: The limitation of current urinary tumor markers is the low specificity and positive predictive value, which clinically manifests as a high false-positive rate. We analyzed the false-positive data of 2 urinary tumor markers, NMP22 and the BTA stat tests. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value after using the exclusion criteria. MATERIALS AND METHODS: A total of 278 symptomatic patients who presented to a urology clinic were asked to submit a single voided urine sample. Each sample was divided into 3 aliquots of which 1 was stabilized with the NMP22 test kit stabilizer and assayed for NMP22, 1 was tested for BTA stat and 1 was sent for cytological examination. All patients subsequently underwent office cystoscopy and bladder biopsy if indicated. RESULTS: Of the 278 symptomatic patients 112 presented with microscopic hematuria, 77 gross hematuria and 89 chronic symptoms of urinary frequency or dysuria. Of 34 cases (12%) of histologically confirmed bladder cancer NMP22 detected 28 (82.4%), BTA stat 23 (67.7%) and cytology only 10 (29.4%). When atypical cytologies were considered positive, cytology then detected 19 cases (55.9%). Elevated NMP22 values were positive in 28 cases and false-positive in 44 for a specificity of 82% and a positive predictive value of 38.9%. Similarly, BTA stat test was positive in 23 cases and false-positive in 43 for a specificity of 82.4% and a positive predictive value of 34.9%. When atypical cytologies were considered positive, the specificity and positive predictive value were 93% and 55.9%. Greater than 80% of the false-positive results were clinically categorized as benign inflammatory or infectious conditions, renal or bladder calculi, recent history of a foreign body in the urinary tract, bowel interposition segment, another genitourinary cancer or an instrumented urinary sample. A category of "no known pathology" was included in analysis as a control. History of ureteral stents or any bowel interposition segment had a 100% false-positive rate. Exclusion of all 6 clinical categories improved the specificity and positive predictive value of NMP22 (95.6%, 87.5%) and BTA stat (91.5%, 69.7%), and was similar to urinary cytology. CONCLUSIONS: Awareness and exclusion of the categories of false-positive results can increase the specificity and enhance the clinical usefulness of NMP22 and BTA stat tests. Similarly, treating an atypical cytology as positive can enhance the sensitivity and usefulness of urinary cytology.

Antigens, Neoplasm↗
PubMed1999

Effect of angiotensin-converting enzyme therapy on QT interval dispersion.

Patients with chronic heart failure (CHF) have an increased risk for sudden death. This increased risk has been associated with increased QT dispersion (QTd), a reflection of the heterogeneity in ventricular repolarization. Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease heart size as well as decreasing morbidity and mortality in moderate-to-severe CHF. The aim of this study was to determine if ACE therapy is associated with a decrease in QTd, a marker for increased electrical instability. Ninety-seven patients were evaluated. The normalized QTd after 2 months of ACE therapy decreased from 16 +/- 4 to 12 +/- 3, a 25% reduction in dispersions. QTd also decreased from 61 +/- 14 to 47 +/- 12 (P < .001) and QTc dispersions decreased from 71 +/- 18 to 52 +/- 14 (P < .001). After 2 months of ACE inhibitor therapy, heart rate slowed significantly (RR intervals 765 +/- 198 before and 838 +/- 186 after ACE). There was a negative correlation between ejection fraction and QTd (r = -0.8; P < .001). The study also found no correlation between ACE level, percent converting enzyme inhibition, and QTd. The effects of ACE therapy appear early on in terms of repolarization changes. The reduction in QTd may explain the reduced sudden death mortality in patients with heart failure who are treated with ACE inhibitor therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells.

The endothelium of the lung is sensitive to the toxic effects of oxygen, and early evidence of toxicity is characterized by protein leak and extravasation of red blood cells. The overproduction of oxygen free radicals plays a critical role in the pathophysiology of a hyperoxic lung injury. Recently, heme oxygenase 1 (HO-1), the rate-limiting enzyme in the metabolism of heme, has been found to have a protective role in oxidant injury. Our laboratory and others have identified HO-1 as a hyperoxia-inducible protein. In this study, we characterized HO-1 expression and evaluated its regulation in human pulmonary endothelial cells. Hyperoxia results in a relatively small increase in HO-1 expression; however, this induction is potentiated by heme and dramatically potentiated in the presence of free iron. This is probably more reflective of the in vivo situation in which there is extravasation of heme and iron products. We also found that HO-1 expression depended on chelatable iron. The iron chelator desferrioxamine not only inhibited the iron- dependent potentiation of HO-1 in response to hyperoxia but also inhibited both hyperoxia and basal expression. On the basis of inhibitor studies and nuclear run-on assays, we demonstrated that this induction is transcriptionally dependent. We also evaluated 4.5 kb of the human HO-1 promoter region and demonstrated that this region has promoter activity to the stimulus heme; however, there was no evidence of promoter activity to either iron or hyperoxia. This diversity of promoter activity to heme, heavy metals, and hyperoxia is unique to the human HO-1 gene.

Cathepsins↗
PubMed1999

NMP22 is a sensitive, cost-effective test in patients at risk for bladder cancer.

PURPOSE: The early diagnosis of bladder cancer is central to its effective treatment. This study was designed to determine the clinical use of NMP22 as a urinary marker for the early detection of transitional cell carcinoma of the bladder in patients with hematuria or other indications at risk for malignancy. The sensitivity and specificity of the NMP22 test were compared with urinary cytology, and the results of both tests were then compared to cystoscopic findings. We also determined if NMP22 provided a cost advantage over our current modalities in our patient population. MATERIALS AND METHODS: Each patient submitted a single voided urine which was divided in 2 parts, of which 1 was stabilized with the NMP22 urine collection kit and 1 was preserved in the appropriate cytology medium for cytopathological testing. All patients provided the urine samples before cystoscopic examination. Of the 330 patients 114 (34.5%) presented with microscopic hematuria and 66 (20.4%) with gross hematuria. Other indications for cystoscopy included atypical cytology or unexplained voiding symptoms refractory to medical therapy. RESULTS: There were 18 patients with biopsy confirmed bladder cancer and 312 with benign conditions of the bladder. Median NMP22 value for the malignant bladder tumors was 31.6 units per ml. (95% confidence interval 13.4 to 90.9) and 4.3 units per ml. (3.8 to 4.8) for benign conditions of the bladder. The urinary NMP22 values in the bladder cancer group were significantly higher than those in the benign condition group (p <0.001). The sensitivity of NMP22 was 100% with a specificity of 85% at a reference value of 10.0 units per ml., while cytology had a sensitivity of only 33% and specificity of 100%. Given a negative predictive value of 100% for NMP22, a cost savings of $28,302 to $111,072 (depending on the type of insurance carrier) would have been achieved if it was used alone as the indication for cystoscopy. CONCLUSIONS: This study indicates that urinary NMP22 is a simple, noninvasive, cost-effective marker for the detection of bladder cancer.

Aged↗
PubMed1999

Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity.

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 1 x 10(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.

Adult↗
PubMed1999

Patient characteristics associated with vasectomy reversal.

PURPOSE: More than 30 million couples throughout the world are using vasectomy as a method of birth control. It is estimated that up to 6% of men who undergo voluntary sterilization will eventually request reversal, despite the high cost and relatively low success rate of the procedure. We identified characteristics that predict which vasectomy patients may request reversal. We also examined the cost and effectiveness of pre-vasectomy sperm cryopreservation followed by intrauterine insemination as an alternative method of achieving pregnancy. MATERIALS AND METHODS: We reviewed medical charts of 365 patients who underwent vasectomy and 290 who underwent vasectomy reversal between 1990 and 1997. Data were collected on patient age at the time of vasectomy, religion, occupation, wife employment status, number of marriages, number of children, reason for reversal, and number of years between vasectomy and reversal. Based on previously reported values, pregnancy rates and cost per successful pregnancy were estimated for vasectomy reversal surgery, and compared with a calculated cost per pregnancy for sperm cryopreservation and intrauterine insemination. RESULTS: Patient factors significantly associated with increased vasectomy reversal included younger age at time of vasectomy (p < 0.001) and a wife who worked outside the home (p < 0.001). Vasectomy reversal occurred 12.5 times more often (95% confidence interval [CI] 7.6 to 20.7) in men who underwent vasectomy in their 20s than in men who were older. Men whose wives were not employed requested reversal 0.48 times as often (95% CI 0.33 to 0.71) as those whose wives worked. Men who were younger at vasectomy tended to wait longer before reversal (median 10 years) than other patients (p < 0.001). At 10 years our calculated pregnancy rates and cost per pregnancy were 44% and $12,727 for vasectomy reversal, and 41% and $9,512 for intrauterine insemination with banked sperm (3 attempts). CONCLUSIONS: Patients who requested vasectomy reversal most often chose voluntary sterilization at a younger age. We believe that younger men should be given better pre-vasectomy counseling. However, the success rate and cost-effectiveness of sperm cryopreservation before vasectomy, with subsequent intrauterine insemination, may make this nonsurgical alternative desirable for younger couples who choose vasectomy even when properly informed about reversal rates.

Adult↗
PubMed1999

Fertility outcome after repeat vasoepididymostomy.

PURPOSE: Historically, epididymal obstruction has been treated with surgical reconstruction. We determine whether it is worthwhile for patients to undergo repeat surgical reconstruction after failed vasoepididymostomy or whether they should be advised only to undergo sperm acquisition for assisted reproductive technique. MATERIALS AND METHODS: A total of 18 patients underwent repeat vasoepididymostomy performed by a single urologist (A. J. T.). Cases were divided based on the etiology of obstruction into groups 1--prior vasectomy (4), 2--congenital (7) and 3--inflammatory (7). Data were available regarding time of obstruction between initial and repeat vasoepididymostomy, quality of epididymal fluid, levels of anastomoses, semen analyses at least 12 months after surgery for all 18 men and pregnancy rates based on more than 18 months of followup in 12. RESULTS: Mean patient age at repeat vasoepididymostomy was 40.6 years (50.5, 36 and 39.4 years for groups 1, 2 and 3, respectively). Mean interval between vasectomy and initial vasoepididymostomy was 12.3 years (range 10 to 18). Mean interval between initial and repeat vasoepididymostomy was 19 months (range 12 to 41). Of the patients 10 underwent unilateral and 8 bilateral anastomoses, for a total of 26 repeat anastomoses. Overall patency rate was 66.7% (12 of 18) with sperm in the ejaculate in 75, 85 and 43% of patients in groups 1, 2 and 3, respectively. The patency rates according to the levels of the anastomosis were 66.7, 62.5 and 100% in the caput, corpus and cauda, respectively. Natural conception occurred in 3 of 12 couples (25%, 2 caput and 1 caudal anastomosis) during a mean followup of 23 months (range 13 to 34). All 3 cases had congenital obstruction. Pregnancy was achieved in 2 group 1 cases with cryopreserved sperm extracted at repeat vasoepididymostomy, and in 1 case each in groups 1 and 2 with microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection. CONCLUSIONS: After repeat vasoepididymostomy two-thirds of men have sperm in the semen. Natural conception occurred in 25% of patients (3 of 12) followed for more than 18 months. Inability to establish pregnancy in the remaining 7 of 9 patients with sperm in the semen with a followup longer than 18 months may be due to epididymal dysfunction or partial obstruction and subsequent poor sperm quality. Aspiration of motile sperm and cryopreservation were possible in 11 of 18 cases at repeat vasoepididymostomy and should be recommended in case azoospermia remains or occurs after surgery. It appears worthwhile to offer patients repeat vasoepididymostomy after a failed initial procedure.

Adult↗
PubMed1999

Adjuvant therapy in invasive thymoma: an audit of cases treated over an 8 year period.

Invasive thymomas comprise 0.1%-0.2% of all malignancies in India. This report is an audit of 11 cases (10 males and 1 female) at a mean age of 36.6 years (range 25-52 years) of invasive thymoma accrued over an eight year period treated by combined modality treatment. Nine of these presented with myaesthenia gravis. All patients underwent initial surgery (3 partial and 8 total resections) and postoperative radiotherapy. Two of the three partially resected patients received one course of chemotherapy prior to radiotherapy consisting of cyclophosphamide, vincristine, procarbazine and prednisolone. At a median follow up of 28 months (range 2-87) there have been no local relapses, one distant metastasis and one death due to uncontrolled myaesthenia. The treatment strategies with invasive thymomas would depend upon the extent of resection. Postoperative radiotherapy appears to be indicated in all cases, however the role of chemotherapy may be limited to those with partial resection.

Adult↗
PubMed1999

Visual outcome in optic nerve injury patients without initial light perception.

PURPOSE: To assess the prognosis for recovery of vision in patients with blindness due to head injury, and to analyse the predictive value of visual evoked potential (VEP). METHODS: One hundred consecutive patients with unilateral/bilateral blindness as a result of minor head injury were studied with regard to their visual status, CT scan, MRI scan and serial VEPs. Steroids were given to those presenting within one month of injury, 5 patients among them received methyl prednisolone. Transethmoidal decompression was done in 6 patients. RESULTS: Visual improvement was recorded in 23 patients. Initial VEP failed to reveal any wave in 29 patients and was abnormal in 71. All the 14 patients in whom VEPs were repeatedly normal, irrespective of initial VEP status, showed varying degrees of visual improvement and none of the 15 patients with persistently negative VEPs showed visual improvement. CONCLUSION: Recovery of VEP from no response to abnormal wave or abnormal wave to normal VEP were indicators of relatively good visual prognosis. Overall, 23 patients showed visual improvement, but did not return to normal. Mode of injury, CT findings and timing of surgery did not influence the outcome.

Adolescent↗