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Biomedical subjects

P Narayan

Publications and source records attributed to P Narayan.

At least 19 recordsLinked to original sources
PubMed1998

Effects of moderate intensity exercise on serum lipids in African-American men with severe systemic hypertension.

The prevalence of systemic hypertension and its cardiovascular consequences is higher in African-Americans than in whites. Low to moderate intensity aerobic exercise lowers blood pressure (BP) in African-American patients with severe hypertension. It is not known whether such exercise can improve lipid metabolism in these patients. Thirty-six African-American men with established essential hypertension, aged 35 to 76 years, were randomly assigned to an exercise (n = 17) or no exercise (n = 19) group. The exercise group exercised for 16 weeks, 3 times/week, at 60% to 80% of maximum heart rate. After 16 weeks, peak oxygen uptake in the exercise group improved (21+/-4 vs 23+/-3 ml/kg/min; p <0.001). Body weight did not change. Exercise intensity correlated with high-density lipoprotein (HDL) cholesterol changes from baseline to 16 weeks (r = 0.65; p <0.01) and was the strongest predictor of these changes (R2 = 0.4; p = 0.009). Lipoprotein-lipid changes in the 2 randomized groups did not differ significantly. A 10% increase in HDL cholesterol--42+/-19 versus 46+/-19 mg/dl; p = 0.003--noted in 10 patients who exercised > or = 75% of maximal heart rate suggested the existence of an exercise intensity threshold. Thus low to moderate intensity aerobic exercise may not be adequate to modify lipid profiles favorably in patients with severe hypertension. However, substantial changes in HDL cholesterol were noted in patients exercising at intensities > or = 75% of age-predicted maximum heart rate, suggesting an exercise-intensity threshold.

Adult↗
PubMed1998

31P-NMR analysis of congestive heart failure in the SHHF/Mcc-facp rat heart.

31P-NMR was used to monitor myocardial bioenergetics in compensated and failing SHHF/MCC-fa(cp) (SHF) rat hearts. The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is a relatively new genetic model in which all individuals spontaneously develop congestive heart failure, most during the second year of life. Failing SHF rat hearts displayed a pronounced decrease in resting PCr:ATP ratios (P<0.001), which was explained by a significant (P<0. 0001) drop in total creatine (47.2+/-3.1 nmol/mg protein) v age matched controls (106+/-3 nmol/mg protein). In end stage failure, NMR determined PCr was 2.9+/-0.1 micro mol/g wet weight under basal conditions. In contrast, 6- and 20-month-old controls and compensated SHFs had PCr values of 5.3+/-0.1, and 5.1+/-0.5 and 5. 1+/-0.2 micro mol/g wet weight. Both compensated and failing SHF hearts were metabolically compromised when the rate pressure product (RPP) was increased, as evidenced by an increase in Pi and a drop in PCr. Compensated SHF hearts, however, were able to increase rate pressure products (RRP, mmHg X beats/min) from 44.5+/-1.4 to 66.6+/-3. 4 K with dobutamine infusion, whereas hearts in end-stage failure were able to increase their RPP from baseline values of 27+/-4 K to only 37+/-7 K. The data indicate that a pronounced decline in PCr and total creatine signals the transition from compensatory hypertrophy to decompensation and failure in the SHF rat model of hypertensive cardiomyopathy.

Adenine Nucleotides↗
PubMed1998

Adenosine A1 receptor stimulation antagonizes the negative inotropic effects of the PKC activator dioctanoylglycerol.

It has been suggested that adenosine cardioprotection occurs via adenosine A1 receptor-mediated activation of protein kinase C (PKC). However, adenosine has well-known vasodilatory effects in the myocardium, whereas PKC is a vasoconstrictor. This study examined whether adenosine A1 receptor activation alters the effects of the PKC activator. 1,2-dioctanoyl-s,n-glycerol (DOG) in isolated perfused rat hearts (left-ventricular developed pressure) and rat ventricular myocytes ([Ca2+]i and cell shortening). Exposure to DOG decreased left-ventricular developed pressure by 30%, an effect that was completely reversible. Pretreatment of isolated hearts with either the PKC inhibitor chelerythrine or the adenosine A1 agonist 2-chloro-N6-cyclo-cyclo-isolated pentlyadenosine (CCPA) attenuated the negative inotropic effects of DOG. In the isolated myocytes, DOG decreased [Ca2+]i and cell shortening by 25 and 28%, respectively, effects that were attenuated by both chelerythrine and CCPA. The CCPA attenuation of the DOG-induced decrease in [Ca2+]i and cell shortening was blocked by pretreating the myocytes with the adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results indicate that in rat ventricular myocardium, adenosine A1 receptor activation attenuates the apparent PKC-dependent negative inotropic effects of DOG via preservation of [Ca2+]i levels.

Adenosine↗
PubMed1998

Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels. HIT Investigators. Department of Veterans Affairs HDL Intervention Trial.

BACKGROUND: The Veterans Administration-HDL Intervention Trial is an ongoing, 20-center, randomized, double-blind, placebo-controlled study aiming to assess the effect of gemfibrozil-improved low high-density lipoprotein cholesterol levels on cardiovascular morbidity and mortality rates. METHODS AND RESULTS: Eligible patients were men with low high-density lipoprotein cholesterol levels and demonstrable coronary heart disease. A total of 2531 patients (average age 63.5 years) were randomly assigned in this study, with a mean high-density lipoprotein cholesterol level of 0.83 mmol/L (32 mg/dL) and low-density lipoprotein cholesterol level of 2.87 mmol/L (111 mg/dL). Baseline data provided the opportunity to assess the interaction of several coronary heart disease risk factors and comorbid vascular diseases. Of these patients, 206 had diabetes mellitus (DM) alone, 1021 had hypertension (HTN) alone, 421 had both DM and HTN, and 883 had neither ("others"). Considering the influence of these risk factors on comorbidities independent of smoking status, patients with DM alone had a 2-fold increase in the prevalence of peripheral vascular disease and a 1.5-fold increase in congestive heart failure. Patients with HTN had a significant increase in the prevalence of cerebrovascular disease, stroke, and congestive heart failure. Patients with HTN and DM had a significant increase in all comorbidities. Smoking resulted in substantial increase of both peripheral vascular disease and cerebrovascular disease. Compared with nonsmoking patients with no DM or HTN, patients with DM and HTN and smoking had a 3-fold increase in the prevalence of peripheral vascular disease and a 3.5-fold increase in cerebrovascular disease (P < .001). CONCLUSIONS: We conclude that DM is a strong correlate of peripheral vascular disease, hypertension of cerebrovascular disease, and that there is a strong additive effect between DM, HTN, and smoking on both.

Aged↗
PubMed1998

Novel staging tool for localized prostate cancer: a pilot study using genetic adaptive neural networks.

PURPOSE: An estimated $1.5 billion is spent annually for direct medical expenses and an additional $2.5 billion for indirect costs for the management of prostate cancer. Today there are several procedures for staging prostate cancer, including lymph node dissection. Despite these procedures, the accuracy of predicting extracapsular disease remains low (range 37 to 63, mean 45%). Use of multiple staging procedures adds significantly to the costs of managing prostate cancer. Recently artificial intelligence based neural networks have become available for medical applications. Unlike traditional statistical methods, these networks do not assume linearity or homogeneity of variance and, thus, they are more accurate for clinical data. We applied this concept to staging localized prostate cancer and devised an algorithm that can be used for prostate cancer staging. MATERIALS AND METHODS: Our study comprised 1,200 men with clinically organ confined prostate cancer who underwent preoperative staging using serum prostate specific antigen, systematic biopsy and Gleason scoring before radical prostatectomy and lymphadenectomy. The performance of the neural network was validated for a subset of patients and network predictions were compared with actual pathological stage. Mean patient age was 62.9 years, mean serum prostate specific antigen 8.1 ng./ml. and mean biopsy Gleason 6. Of the patients 55% had organ confined disease, 27% positive margins, 8% seminal vesicle involvement and 7% lymph node disease. Of margin positive patients 30% also had seminal vesicle involvement, while of seminal vesicle positive patients 50% also had positive margins. RESULTS: The sensitivity of the network was 81 to 100%, and specificity was 72 to 75% for various predictions of margin, seminal vesicle and lymph node involvement. The negative predictive values tended to be relatively high for all 3 features (range 92 to 100%). The neural network missed only 8% of patients with margin positive disease, and 2% with lymph node and 0% with seminal vesicle involvement. CONCLUSIONS: Our study suggests that neural networks may be useful as an initial staging tool for detection of extracapsular extension in patients with clinically organ confined prostate cancer. These networks preclude unnecessary staging tests for 63% of patients with clinically organ confined prostate cancer.

Algorithms↗
PubMed1998

Transurethral needle ablation for benign prostatic hyperplasia: 12-month results of a prospective, multicenter U.S. study.

OBJECTIVES: To report the safety and efficacy of the transurethral needle ablation (TUNA) procedure for the treatment of clinical benign prostatic hyperplasia (BPH). METHODS: One hundred thirty patients with BPH were enrolled in two identical protocols and treated by the TUNA procedure. Entry criteria included an American Urological Association symptom index (AUA SI) of 13 points or higher and a peak flow rate of 12 mL/s or less. Patients were followed up for 12 months. Efficacy parameters included the AUA SI, AUA problem index, BPH impact index (BPH II), quality of life (QOL) score, and peak flow rate. At each visit, side effects were elicited. Follow-up data are available for 93 patients at 12 months. All patients were given intraurethral lidocaine augmented by oral and/or parenteral sedation. No patient received spinal or general anesthesia. RESULTS: All patients tolerated the procedure well, and there were no deaths. Forty-one percent of patients (n = 53) had a catheter placed immediately after the procedure. At 12 months, the AUA SI had decreased from 23.7 to 11.9 (P < 0.0001) and the BPH II from 7.5 to 2.5 (P < 0.0001), whereas the peak flow rate had increased from 8.7 to 14.6 mL/s (P < 0.0001). Irritative voiding symptoms were noted in 20 patients (16%) at some point during follow-up. Two patients reported erectile dysfunction, and 1 reported retrograde ejaculation. CONCLUSIONS: In this prospective study of 130 patients with clinical BPH and lower urinary tract symptoms, TUNA provided substantive and lasting improvement according to AUA SI, BPH II, and QOL scores as well as peak flow rate over 1 year. The TUNA procedure was well tolerated, with few major side effects and complications noted. Longer follow-up is needed to document the maintenance of clinical benefit beyond 12 months.

Aged↗
PubMed1998

Overview of alpha-blocker therapy for benign prostatic hyperplasia.

Management of benign prostatic hyperplasia (BPH) is rapidly changing. Established surgical procedures are being replaced by minimally invasive modalities such as electrovaporization and transurethral needle ablation. Improved understanding of pathophysiology and developments in molecular biology has provided drugs for alleviating the symptoms of prostatic enlargement. Currently, medical therapy is the first-line treatment modality in the management of BPH. There are two types of medical treatment available: alpha-adrenoceptor-blockers and 5-alpha-reductase inhibitors. Alpha-blockers relieve the dynamic component of obstruction whereas 5-alpha-reductase inhibitors relieve the mechanical component of obstruction. At present, alpha-blockers are used most frequently. However, they do have significant cardiovascular side effects. More uroselective alpha-blockers have recently become available and may reduce the risk of cardiovascular side effects. This review summarizes relevant literature on the use of alpha-blockers in the treatment of BPH.

Adrenergic alpha-Antagonists↗
PubMed1998

Surface retention of an inactivating lutropin receptor mutant in exoloop 3.

The heptahelical lutropin receptor (LHR) signals primarily via the Gs-adenylyl cyclase pathway and undergoes ligand-mediated receptor desensitization and internalization. A loss-of-function rat LHR mutant was recently described in which a single amino acid residue replacement in exoloop 3, K583E, had no effect on human choriogonadotropin (hCG) binding but essentially abolished signaling. This LHR mutant is a prime candidate for which to study hCG-mediated receptor internalization since it is highly unlikely that an amino acid residue in exoloop 3 , i.e. an extracellular portion of LHR connecting transmembrane helices 6 and 7, could have any direct interaction with Galpha(s), which is located on the cytoplasmic face of the plasma membrane. A method to study endocytosis was adapted that involves concanavalin A binding to the glycoproteins on the cell surface, thus facilitating separation of the plasma membrane fraction from other cellular membrane fractions by sucrose gradient centrifugation. Conditions were used such that a single round of endocytosis could be determined with [125I]hCG. Endocytic rate constants of 0.03 and O min(-1) were obtained for LHR and the mutant, respectively, in transfected human embryonic kidney 293 cells; moreover, internalization of the mutant could not be restored by the addition of 8-Br-cAMP. Thus, the presence of the second messenger cAMP is not sufficient for internalization of ligand-occupied LHR. Rather, it appears that ligand-mediated activation and subsequent internalization of LHR results from an altered conformational state or a conformation-dependent post-ligand binding modification such as phosphorylation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Minimally invasive therapies for the treatment of symptomatic benign prostatic hyperplasia: the University of Florida experience.

OBJECTIVE: To describe the University of Florida experience with minimally invasive therapies in the surgical treatment of benign prostatic hyperplasia (BPH). BACKGROUND DATA: Typically, the standard surgical treatment for symptomatic benign prostatic hyperplasia (BPH) has been transurethral resection of the prostate (TURP). Due to the morbidity associated with TURP, several minimally invasive therapies, such as laser, microwaves, high intensity focused ultrasound, and radiofrequency needle ablation, have been utilized to treat BPH. METHODS: The authors review their experience, along with that of others, with various forms of heat therapy in the treatment of BPH. RESULTS AND CONCLUSIONS: Although high intensity focused ultrasound (HIFU), interstitial laser, and microwaves procedures have been shown to be effective in the treatment of BPH, our experience has been with laser, VaporTrode, and TUNA. We found that VaporTrode and TUNA currently offer several advantages over many of the other modalities.

Electrosurgery↗
PubMed1998

Prostatectomy tissue for research: balancing patient care and discovery.

The application of modern technology in basic research often requires fresh tissue from human organs. The acquisition of this tissue challenges the anatomic pathologist to balance the needs of the basic scientist with the requirements of quality patient care. Our experience indicates that fresh tissue adequate for research can be obtained from neoplastic prostate glands without compromising patient care. The process requires dedicated, knowledgeable individuals and extensive documentation. Potential problems include low yield for research studies, loss of all residual carcinoma, compromise of the specimen margin, and unforeseen costs. Best collaborations occur in situations in which basic scientists and anatomic pathologists establish a working relationship and develop a mutually supportive means of funding.

Antineoplastic Agents, Hormonal↗
PubMed1998

The endothelin subtype A receptor undergoes agonist- and antagonist-mediated internalization in the absence of signaling.

The potent vasoconstrictor and mitogen to smooth muscle cells, endothelin-1 (ET-1), acts via two distinct G protein-coupled receptors, subtype A (ETAR) and subtype B, that are coupled primarily to the Gq-phospholipase C signaling pathway. It is known that ET-1 binding to ETAR promotes internalization, with subsequent degradation of at least a portion of the bound ligand. To investigate whether signaling is required for endocytosis, we developed stably transfected lines of human embryonic kidney 293 cells expressing wild-type ETAR and a receptor chimera (ETARC) in which the C-terminal cytoplasmic tail to ETAR was replaced with that of the lutropin receptor, another G protein-coupled receptor, but one which signals through the Gs-adenylyl cyclase pathway. ETARC binds ET-1 like ETAR, but is deficient in signaling. Using a combined concanavalin A/sucrose gradient centrifugation technique to separate plasma membranes from other cellular membranes, we found that [125I]ET-1 is rapidly internalized into ETAR-expressing cells at 37 C (t1/2 for internalization = 5 min; endocytic rate constant = 0.1 min(-1); ETARC-expressing cells also internalize [125I]ET-1, albeit at a somewhat slower rate than wild-type receptor (t1/2 for internalization = 15 min; endocytic rate constant = 0.03 min(-1). Using immunofluorescence confocal microscopy and an antibody developed to the N-terminal region of ETAR, qualitatively similar results were obtained. In addition, it was found using confocal microscopy that the ETAR-selective antagonist, BQ123, also promoted rapid internalization in cells expressing ETAR. These results establish that inositol 1,4,5-trisphosphate signaling is not required for ligand-mediated internalization of ETAR and suggest that a receptor conformational change is necessary. Moreover, the finding that BQ123 promotes ETAR internalization is novel and has potentially important implications in its clinical use.

Biological Transport↗
PubMed1998

Systematic biopsy-based staging of prostate cancer: scientific background, individual variables, combination of parameters, and current integrative models.

Staging of the prostate cancer remains the mainstay of treatment decisions and prognostication. Multiple staging tests, which are currently available, fail to provide optimal staging accuracy in the management of prostate cancer. Systemic biopsy can provide useful data regarding bilaterality, Gleason grade, cancer map, perineural infiltration, tumor volume, percentage cancer and microvessel density. We have reviewed existing literature on systematic biopsy in this review. We have further discussed the role of neural network technology in integrating this information.

Biopsy↗
PubMed1998

An open study on the efficacy and safety of transurethral needle ablation of the prostate in treating symptomatic benign prostatic hyperplasia: the University of Florida experience.

PURPOSE: We determine the safety and efficacy of transurethral needle ablation of the prostate in patients with moderate to severe symptoms of benign prostatic hyperplasia. MATERIALS AND METHODS: Transurethral needle ablation of the prostate was performed on 45 consecutive patients. For an average prostate of 2.5 to 3 cm. long treatments were performed in 2 separate planes at 4 quadrants (2, 4, 8 and 10 o'clock positions) each. The 2 planes were 1 cm. below the bladder neck and 1 cm. proximal to the verumontanum. For prostatic urethral lengths longer than 3 cm. a treatment plane was added for each additional centimeter of prostatic urethra. The procedure was performed in 26 patients under local anesthesia using 20 cc 2% intraurethral lidocaine gel (11) or supplemented with intravenous 1.25 to 5 mg. midozolam (15). Of these patients 2 had a supplemental perineal block using a mixture of equal amounts of 15 cc 2% lidocaine without epinephrine and 0.25% bripivacaine, 10 underwent the procedure under general anesthesia, 2 had epidural and 4 had spinal anesthesia, and 3 had managed anesthesia care. Mean length of each procedure was 79 minutes (range 50 to 240). All procedures were done on an outpatient basis and patients were released on the same operative day. RESULTS: Mean prostatic volume on transrectal ultrasound was estimated at 48.1 cc (range 20 to 185). Following treatment the International Prostate Symptom Score decreased from a mean of 20.9 at baseline to 15.4 at 1 month, 16.1 at 3 months, 10.7 at 6 months and 9.9 at 1 year. The peak flow rate improved from a baseline mean of 8.3 to 13.4 at 3 months, 13.1 at 6 months and 14.9 at 1 year. The quality of life score improved from a baseline of 4.8 to 3.5, 2.2, 2.5 and 1.03 at 1, 3, 6 and 12 months, respectively. Of the 2 patients in whom the procedure failed; 1 required a bladder neck incision at 3 months and the other transurethral resection of the prostate. Foley catheters were left in place in all patients for an average of 4.85 days. CONCLUSIONS: After a followup of up to 12 months we conclude that transurethral needle ablation of the prostate is an effective treatment for symptomatic benign prostatic hyperplasia. This procedure has minimal morbidity, is less costly than conventional transurethral resection of the prostate and can be performed as an outpatient office procedure under local anesthesia in a significant number of patients.

Aged↗
PubMed1998

A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group.

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.

Adrenergic alpha-Antagonists↗
PubMed1998

Tamsulosin: the United States trials.

Overall, tamsulosin has several advantages. Its long-acting action allows for once-daily dosing. The therapeutic effect, as indicated by > 30% increase in peak urinary flow rate, is realized in more than 50% of the patients receiving the therapy. The beneficial effect from treatment is seen as early as 2 to 3 weeks after the maximum dose is reached. In addition, the dose may be adjusted from 0.4 mg daily to 0.8 mg daily to obtain the desired decrease in urinary tract obstructive symptoms, although the vast majority of patients are effectively treated with 0.4 mg daily. Also, there is no known effect of alpha 1-adrenergic antagonists on the serum PSA concentration. The incidence of untoward cardiovascular system effects is less important because of tamsulosin's uroselective action. As with any other medical therapy for BPH, tamsulosin must be taken indefinitely to maintain the therapeutic effect.

Adrenergic alpha-Antagonists↗