Discovery of a novel class of orally active, non-peptide angiotensin II antagonists.
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Biomedical subjects
Publications and source records attributed to R Warner.
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Dopamine (DA) in the medial preoptic area (MPOA) has been shown to facilitate male rat sexual behavior. However, injections of the catecholamine (CA) neurotoxin 6-OHDA into the MPOA did not impair copulation in tests 3 days after injection. In the present study, three weekly (serial) injections produced no copulatory deficits compared to animals that received a single injection or to preinjection copulatory behavior scores. However, blocking CA synthesis, which did not impair control rats, produced deficits in both single and serial lesion animals, with significantly fewer serial than single lesion animals initiating copulation. Biochemical analysis of tissue punches showed no difference in MPOA concentrations of dopamine, norepinephrine, epinephrine, or the dopamine metabolite DOPAC between the two groups. Additional animals were tested at earlier intervals after 6-OHDA injections into the MPOA. Tests conducted 30 min after an MPOA injection of 6-OHDA revealed that all measures of copulation were impaired, relative to scores 24 h later. However, these scores were not significantly different from animals tested 30 min after a vehicle injection. A final group, tested 4 h after injection, showed impairment of all measures of copulation compared to vehicle injections and to tests 24 h later. Furthermore, in the tests 24 h later, 6-OHDA animals were not different from vehicle animals. Results from all experiments show that 6-OHDA injections into the MPOA impair copulation for at least 4 h, but that behavioral recovery is complete 24 h later. However, deficits can be reinstated by inhibiting DA synthesis, suggesting that increased synthesis in undamaged terminals contributed to behavioral recovery.
Two scales developed in Great Britain, the QOL Profile and the General Satisfaction Questionnaire, were used to examine the relationship between type of case management services and quality of life and satisfaction with treatment of 68 long-term psychiatric patients in Colorado. Factor analysis identified three types of case management activities that tended to occur together: assertive outreach (direct help, out-of-office visits, and monitoring), brokerage (referral to other agencies), and counseling and assessment. Monitoring was the only variable positively associated with quality of life for all patients; brokerage was the only variable negatively associated with acceptability of services. The number of case management contacts was negatively associated with treatment satisfaction.
We installed a ventilation system that minimizes airborne bacteria, dust, humidity, and ammonia levels; conserves animal heat during the winter months by precise control of the amount of fresh air admitted to the calf nursery; and prevents cross transfer of airborne pathogens between neighboring calves by providing uniform air distribution throughout the calf nursery. Because of the effectiveness of air filtration and uniform air distribution within the nurseries, respiratory problems of calves were reduced greatly. Airborne dust and bacteria as small as .5 mu were filtered from the air.
The purpose of this study was to determine whether reperfusion of acute myocardial infarction (AMI) by recombinant tissue-type plasminogen activator (rt-PA) or percutaneous transluminal coronary angioplasty, or both, would improve left ventricular (LV) function when it is measured several months later at rest or maximal bicycle exercise, or both. Radionuclide angiography was performed in 44 patients 5 months (range 6 weeks to 9 months) after AMI to assess function, and tomographic myocardial thallium-201 imaging was performed at maximal exercise and delayed rest to determine whether there was any evidence of myocardial ischemia. As expected, no patient had chest pain or redistribution of a thallium defect during the exercise test, because patients had undergone angioplasty (n = 28) or coronary bypass graft surgery (n = 5) where clinically indicated for revascularization. The LV ejection fraction was plotted as a function of the time elapsed between the onset of chest pain and the time when coronary angiography confirmed patency of the infarct-related artery (achieved in 91% of 44 patients by rt-PA [n = 31] or percutaneous transluminal coronary angioplasty [n = 9] ). Functional responses differed markedly between patients with anterior (n = 20) versus inferior (n = 24) wall AMI. LV ejection fraction during exercise correlated with time to reperfusion in patients with an anterior wall AMI (r = -0.58; standard error of the estimate = 11.9%; p less than 0.02) but not in patients with an inferior AMI (r = 0.10; standard error of the estimate = 13.1%; difference not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Local vascular reconstructions frequently require the use of vein grafts to bridge arterial or venous defects. Most previous studies on the use of cryopreserved veins have used relatively large caliber vessels. There have been few studies on the effectiveness of cryopreserved micro- or small-venous allografts. Here, we tested two types of cryopreserved venous allografts: (1) 1.5- to 1.9-mm diameter microvenous grafts (MVG); and (2) 4- to 5-mm diameter small venous grafts (SVG). Cryopreserved MVG allografts were placed into saphenous arteries of six experimental dogs and SVG cryopreserved allografts were placed into femoral arteries of six experimental dogs for 3 to 6 weeks. Two fresh MVG autografts were also transplanted into experimental dogs as controls and autografts were transferred to the contralateral side in SVG dogs as controls. None of the six cryopreserved MVG grafts retained patency but three/six cryopreserved SVG allografts were patent at harvest. Histological examination of grfts revealed control autografts were undergoing arterialization with an intact intima. Experimental cryopreserved allografts showed extensive medial fibrosis, significant lymphocytic infiltrates, and sporadic areas of intact intima for both patent and nonpatent grafts.
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The experiments described here were intended to investigate whether serotonin (5HT) may be involved in analgesia induced by low current transcranial electrostimulation (TE). The TE stimulus is a 10 mu-ampere, 10 Hz, pulsed current transmitted via electrodes in the pinnae. Combinations of the following were given as intraperitoneal injections: 300 mg/kg p-chlorophenylalanine (pCPA) 48 hours before testing, 100 mg/kg 5-hydroxytryptophan (5HTP) 30 min before testing and the saline vehicle for these drugs. Rats were tested prior to and 30 minutes after TE or sham TE. Testing for analgesia consisted of putting progressively increasing pressure on the rat tail 1/4 inch from the tip with a pneumatically driven, right angle wedge. The amount of pressure at which the rat moved its tail was measured both before and after TE, or sham TE, and recorded as the difference in tolerated peak pressure (DTPP). TE produced analgesia as manifested by a 613 percent increase in DTPP compared with sham TE treatment values. Among TE treated rats, pretreatment with pCPA decreased DTPP 91.5 percent compared with saline control values, indicating 5HT involvement. 5HTP restored TE induced analgesia in pCPA treated rats to the level of saline treated control animals, confirming 5HT involvement.
Chest wall invasion by bronchogenic carcinoma is found in 5% of all cases of pulmonary carcinoma. During the last 3 years, 11 cases of lung cancer with chest wall involvement have been encountered at the Jackson Veterans Administration Medical Center. We reviewed these cases to reassess the role of concomitant resection of the lung and chest wall. From this experience, we have concluded that (1) chest wall involvement is potentially curable; (2) chest wall resection adds little if any morbidity to the procedure; (3) resections of fewer than four ribs usually require only soft tissue coverage, without a prosthesis; (4) patients with squamous cell cancer have longer survival; (5) chest wall resection is highly effective in the relief of pain due to invasion of the chest wall; and (6) survival is greater than in other stage III lung carcinomas and is more closely related to nodal involvement than to chest wall invasion.
A group of 40 select men were studied to assess the value of transrectal ultrasound in the early detection of prostate cancer. All had a benign digital rectal examination and had either irritative lower tract symptoms, hematospermia, microhematuria, or an elevated acid phosphatase. Of the men, 28 had an abnormal ultrasound and underwent a directed prostate needle biopsy to assess the ability to detect clinical Stager A cancer. Eleven men (40%) were found to have cancer, all having hypoechoic lesions. The remainder were found to have benign prostatic hypertrophy (BPH) with hyperechoic lesions predominating (88%). Our results suggest that transrectal ultrasound is a useful and sensitive method for the detection of prostate tumors not clinically evident on digital rectal examination in select patients.
Labeling theory predicts that psychotic patients who accept the label of mental illness will function less well than those who reject their diagnosis. Accepted psychotherapeutic theory suggests the reverse. Two predictive models were tested. Results supported the central hypothesis of the psychotherapeutic model but not that of the labeling model, although some elements of the latter model were affirmed. Besides acceptance of diagnosis, an internal locus of control appears important for good outcome in psychosis.
Over a thirty-month period, a wide variety of common urethral problems were treated on an ambulatory basis, with the neodymium:yttrium-aluminum garnet (Nd:YAG) laser. When used discriminately, laser treatment appears to be an effective modality for the management of selected urethral strictures. Thus far, excellent results have been obtained in 30 of 31 cases of short strictures where laser urethrotomy was performed as the first stricture procedure (average follow-up 10 months). Furthermore, in a series of 36 cases of secondary bladder neck contractures, all of the evaluated patients responded well (average follow-up 7 months). Good results were obtained in only 11 of 48 complicated strictures (average follow-up 14 months). However, while most of these extensive strictures were not eradicated, laser therapy generally produced a documented clinical improvement, comparable to urethrotomy or dilatation, in 15 of these cases. A series of 24 condylomata involving the urethra were treated satisfactorily, with no recurrences (average follow-up 13 months). Laser treatment also has been used successfully for the management of several urethral caruncles, urethral polyps, two meatal hemangiomas, one urethral carcinoma, and a distal duplicated urethra. Recently, the Nd:YAG laser has been applied to the prostatic urethra with vaporization of obstructing median bar hyperplasia. Favorable results have been achieved in 5 of 6 cases treated with a newly developed technique that utilizes direct laser contact. Retrograde ejaculation has not been encountered in these patients (average follow-up 6 months). All of these procedures have been accomplished in the office, largely without urethral catheterization. Lidocaine jelly occasionally supplemented with intravenous sedation provided satisfactory anesthesia.
After 20 mg sublingual nifedipine in 12 men with clinical stable chronic cor pulmonale the mean arterial pressure and systemic vascular resistance fell, cardiac index rose, and mean pulmonary arterial (Ppa) and wedge (Ppaw) pressures, right atrial pressure, and PaO2 remained unchanged. After 20 mg orally every 6 hours for 24 hours in 11 patients, the mean arterial pressure fell further, systemic vascular resistance remained low, and the cardiac index returned to baseline, whereas the Ppa and Ppaw decreased, but the pulmonary vascular driving pressure (Ppa-Ppaw), right atrial pressure, PaO2, and spirometry and ejection fractions remained unchanged. Of eight patients receiving maintenance therapy four developed untoward side effects in 1 to 3 weeks and one was noncompliant. The remaining three patients evaluated at 6 weeks failed to improve and had unchanged resting hemodynamics. Thus in the absence of a potentially reversible hypoxic pulmonary hypertension, nifedipine may not improve pulmonary arterial pressure and cardiac function in clinically stable patients with cor pulmonale.
Sixty-two schizophrenic patients completed the Parental Bonding Instrument (PBI), a measure of perceived parental characteristics, rating their parents on care and protection. PBI ratings were related to a one-year course of illness. Patients who perceived their parents positively tended to experience a milder course of illness if they were in frequent contact with them, and a more severe course if they were not; the reverse was true for patients who perceived their parents negatively. PBI ratings were unrelated to the age at onset of illness. This suggests that patients' perceptions of parental attitudes influence the course of schizophrenia by a current stress effect. The PBI, used alone or in conjunction with other predictors, distinguished good- and poor-outcome cases and appears to be a potentially clinically valuable tool.
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