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Biomedical subjects

R Wesley

Publications and source records attributed to R Wesley.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cardiovascular effects of a non-xanthine-selective antagonist of the A1 adenosine receptor in the anaesthetised pig: pharmacological and therapeutic implications.

OBJECTIVE: To study antagonism of A1 adenosine receptors in an anaesthetised open chest swine model, the selective A1 receptor antagonist, N6-endonorbornan-2-yl-9-methyladenine (N-0861), was examined to see if it attenuates bradycardia, augments reflex tachycardia associated with adenosine infusion, or both. Its effects were compared with those of the non-selective antagonist of adenosine A1 and A2 receptors, 8-(p-sulphophenyl)-theophylline (8-pST). METHODS: Twenty nine pigs were studied. The prolongation of P-R interval mediated by A1 receptors, the increase in left anterior descending coronary artery blood flow mediated by A2 receptors, and decreases in systemic and left ventricular pressures and first derivative of left ventricular pressure (dP/dt) were monitored in each animal assigned to one of three protocols. (1) Adenosine, 40 to 180 micrograms.kg-1.min-1, was infused for more than 6 min before and immediately after rapid infusion of 8-pST, 5 mg.kg-1 intravenously, or a solvent that did or did not contain N-0861, 0.2 mg.kg-1 intravenously (n = 14). (2) In the same animal, we compared N-0861 and 8-pST in reversing responses mediated by A1 and A2 receptors during two 10 min infusions of adenosine separated by a 1 h washout period (n = 7). (3) N-0861 with adenosine (mean dose, 0.4 mg.kg-1) was infused with or without complete autonomic blockade with atropine (2.5 mg.kg-1) and propranolol (2 mg.kg-1) (n = 8). RESULTS: Adenosine prolonged P-R interval (and cycle length in non-paced hearts), increased coronary flow, and decreased calculated coronary resistance. N-0861 alone did not affect any variable, but N-0861 with adenosine prevented or reversed A1 receptor mediated prolongation of P-R interval in paced hearts and cycle length in non-paced hearts and enhanced A2 receptor mediated coronary vasodilatation. Left ventricular dP/dt and rate-pressure product were maintained with N-0861 and adenosine, and N-0861 unmasked a postadenosine reflex tachycardia. Prolonged PR interval, decreased heart rate, and increased coronary flow were prevented or reversed by the non-selective antagonist 8-pST. CONCLUSIONS: Selectivity of N-0861 for the adenosine A1 receptor may, without reducing coronary blood flow, ameliorate bradyarrhythmia and maintain the positive inotropic response when exogenous adenosine is given or when interstitial myocardial adenosine is increased.

Adenine↗
PubMed1993

Evaluation of natural family planning programmes in Liberia and Zambia.

Studies to evaluate use-effectiveness and cost-effectiveness of natural family planning (NFP) were conducted in Liberia and Zambia. The Liberian programme provided uni-purpose NFP services to 1055 clients mainly in rural areas; the Zambian programme provided NFP services integrated with MCH to 2709 clients predominantly in urban areas. The one-year life table continuation and unplanned pregnancy rates were 78.9 and 4.3 per 100 woman-years in Liberia, compared to 71.2 and 8.9 in Zambia. However, high rates of loss to follow-up mandate caution in interpretation of these results, especially in Zambia. More women progressed to autonomous NFP use in Liberia (58%) than in Zambia (35.3%). However, programme costs per couple-year protection were lower in Zambia (US$25.7) than in Liberia (US$47.1). Costs per couple-year protection were higher during learning than autonomy, and declined over time. These studies suggest that NFP programmes can achieve acceptable use- and cost-effectiveness in Africa.

Adult↗
PubMed1993

A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome.

The objective of this study was to develop criteria for the interpretation of a morning ovine CRH stimulation test for the differential diagnosis of ACTH-dependent Cushing's syndrome. Its design was retrospective review, and its setting was the in-patient unit of a tertiary care center. One hundred and eighteen patients with proven Cushing's disease or ectopic ACTH secretion were studied. The percent change in plasma ACTH and cortisol levels after CRH administration (1 microgram/kg BW) was calculated for each patient using 3 combinations of pre-CRH values (-15, -10, -5, and -1 min) and 6 combinations of post-CRH values (15, 30, 45, and 60 min). The diagnostic performance of these 36 sets of response measures was compared. The mean ACTH concentrations 15 and 30 min after CRH increased by at least 35% above the mean basal value at -5 and -1 min in 93 of 100 patients with Cushing's disease, but in none of the 16 patients with ectopic ACTH secretion. This measure gave the best sensitivity (93%) and specificity (100%). The best cortisol criterion was a mean increase at 30 and 45 min of 20% or more above mean basal values at -5 and -1 min, which gave a sensitivity of 91% and a specificity of 88%. We developed a simplified diagnostic test with 100% specificity using ACTH measurements 5 and 1 min before and 15 and 30 min after CRH administration. Although all patients with ectopic ACTH secretion had less than a 35% increase in ACTH, the probability of Cushing's disease was high at all levels of response, indicating that other tests should be performed to confirm the diagnosis.

ACTH Syndrome, Ectopic↗
PubMed1992

Controlled trial of plasma exchange and leukapheresis in polymyositis and dermatomyositis.

BACKGROUND: The therapeutic options for patients with polymyositis or dermatomyositis that is resistant to corticosteroids are limited, unproved, and often toxic. Uncontrolled trials concluded that both plasma exchange and leukapheresis are beneficial, but despite the considerable use of these approaches, proof of their efficacy is lacking. METHODS: Thirty-nine patients with definite polymyositis or dermatomyositis were randomly assigned to receive plasma exchange (replacement of one volume of plasma with 5 percent albumin in saline), leukapheresis (removal of 5 x 10(9) to 10 x 10(9) lymphocytes), or sham apheresis in a double-blind manner, with 12 treatments given over a one-month period. Muscle strength, functional capacity, and serum levels of muscle-associated enzymes were measured before and after the 12 procedures. RESULTS: In each group 3 of 13 patients had improvements in strength and functional capacity. The condition of 3 patients treated with leukapheresis and 1 treated with plasma exchange deteriorated, and it was unchanged in the other 26 patients. Adverse effects of apheresis included the need for a central venous catheter (9 patients), major vasovagal episodes (3 patients), and severe citrate reactions (2 patients). Despite the occurrence of significant reductions in the serum levels of muscle enzymes with plasma exchange (P less than 0.001) and significant decreases in lymphocyte counts with leukapheresis (P = 0.002), there were no significant differences among the three treatment groups in the final muscle strength or functional capacity of the patients. CONCLUSIONS: As treatments for corticosteroid-resistant polymyositis or dermatomyositis, leukapheresis and plasma exchange are no more effective than sham apheresis.

Activities of Daily Living↗
PubMed1992

Cancer control programme in India: opportunities for implementation and evaluation.

Cancer is now being appreciated in India as an emerging public health problem. Approximately 600,000 new cancer cases occur in India every year, and the absolute number of new cancer patients will increase considerably, due to growth in the size of the population and an increase in the proportion of elderly persons due to improved life expectancy following control of communicable diseases. This emerging problem has received the attention of the Government of India, and some state governments within the Indian Federation have formulated National and State Cancer Control Programmes to deal with the situation. In the event of these programmes being implemented, consideration should be given now to measures of evaluation of the activities, as many of the indices, used to monitor programmes in developed countries, such as 15% reduction from peak cancer mortality, or in peak mortality from specific cancers, are not applicable in developing countries like India. Factors such as the pattern of tobacco habits in the community, knowledge, attitude and practice (KAP) patterns regarding cancer in the general population, referral practices, and the national pattern of extent of disease at presentation, gain considerable importance from the evaluation point of view. Our article mainly deals with the sources and the quality of baseline data for such factors and the realistic quantitative goals which could be set for the above factors.

Humans↗
PubMed1992

Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs.

1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.

Animals↗
PubMed1991

Comparison of changes in transit time ultrasound, esophageal Doppler, and thermodilution cardiac output after changes in preload, afterload, and contractility in pigs.

The purpose of this study was to compare how well changes in cardiac output (CO) measured by esophageal Doppler (Doppler) and thermodilution (TD) followed changes in CO measured by transit time ultrasound (TTU). Simultaneous Doppler, TD, and TTU measurements of CO were made before and after changes in preload, afterload, or contractility in seven piglets. Mean changes in each CO method for each type of change in CO were compared by analysis of variance. Changes in TTU CO, TD CO, and Doppler CO were compared by correlation, linear regression, and bias and precision statistics. Of 86 TTU changes in CO greater than 10%, Doppler changed the same direction as TTU 59 times, changed in an opposite direction 6 times, and changes less than 10% 21 times. Thermodilution changed in the same direction as TTU 72 times, in the opposite direction 4 times, and changed less than 10% 10 times. Changes (% delta) in TTU and TD measurements of CO were not significantly different in any group. Changes in Doppler CO and TTU CO were different for two afterload and contractility groups. Percent changes in Doppler CO had a correlation coefficient (r) = 0.74, m = 0.72, and bias (mean % delta Doppler CO - mean % delta TTU CO) = 6.3 +/- 29.7 with % delta TTU CO. Percent changes in TD CO had an r = 0.90, m = 0.92, and bias = 5.7 +/- 19.1 with % delta TTU CO. Cardiac output measured by Doppler underestimated changes in CO due to changes in preload and contractility and exaggerated changes in CO due to changes in afterload.

Analysis of Variance↗
PubMed1988

The amino-terminal signal peptide on the porcine transmissible gastroenteritis coronavirus matrix protein is not an absolute requirement for membrane translocation and glycosylation.

cDNA clones mapping within the first 2601 bases of the 3' end of the porcine transmissible gastroenteritis corona-virus (TGEV) genome were sequenced by the method of Maxam and Gilbert and an open reading frame yielding a protein having properties of the matrix (M or E1) protein was identified. It is positioned at the 5' side of the nucleocapsid (N) gene from which it is separated by an intergenic stretch of 12 bases. The deduced M protein comprises 262 amino acids, has a molecular weight of 29,544, is moderately hydrophobic, and has a net charge of +7 at neutral pH. Thirty-four percent of its amino acid sequence is homologous with the M protein of the bovine coronavirus (BCV), 32% with that of the mouse hepatitis coronavirus (MHV), and 19% with that of the avian infectious bronchitis coronavirus (IBV). Judging from alignment with the BCV, MHV, and IBV M proteins, the amino terminus of the TGEV M protein extends 54 amino acids from the virion envelope which compares with only 28 for BCV, 26 for MHV, and 21 for IBV. Eleven of the sixteen amino-terminal amino acids are hydrophobic and the positions of charged amino acids around this sequence suggest that the first 16 amino acids comprise a potentially cleavable signal peptide for membrane insertion. A similar sequence is not found in the M proteins of BCV, MHV, or IBV. When mRNA from infected cells, or RNA prepared by in vitro transcription of the reconstructed M gene, was translated in vitro in the presence of microsomes, the M protein became translocated and glycosylated. When a protein without the amino-terminal signal peptide was made by translating a truncated version of the M gene transcript, some translocation and glycosylation also occurred suggesting that the amino-terminal signal peptide on the TGEV M protein is not an absolute requirement for membrane translocation. Interestingly, the amino-terminal peptide did not appear to be cleaved during in vitro translation in the presence of microsomes suggesting that a step in virion assembly may be required for proper exposure of the cleavage site to the signal peptidase.

Amino Acid Sequence↗
PubMed1988

Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance.

Thirty-one previously untreated patients with Ewing's sarcoma were treated with an intensive chemotherapy program of vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cyclosphosphamide (VADRIAC) in combination with radiation therapy to the primary site (greater than 50 Gy) and bone metastases (45 to 50 Gy). An intensified regimen with one further cycle of chemotherapy (VADRIAC), total body irradiation (TBI), and autologous bone marrow transplantation was given to patients with primary tumors of the pelvis, humerus, femur, and chest wall without metastases and to all patients with metastases at diagnosis. Patients with primary tumors of the distal extremity and other sites without metastases at diagnosis were treated on a less intensive chemotherapy regimen of VADRIAC without the intensification. Therapy was completed within 6 to 7 months in all patients. Thirteen patients had metastatic disease at diagnosis; only two of these had the lung as the sole site of metastatic disease. Eighteen patients had no evidence of metastatic disease at diagnosis: ten of these patients had tumors that arose in central axis and proximal extremity sites, and eight had tumors that arose in distal extremity and other sites. Thirty of the 31 patients achieved a complete remission, although two patients underwent amputation: one before chemotherapy and radiation and one after chemotherapy and radiation because of persistent local disease. Seventeen remain in their first complete remission at a median time on study of 30 months and a median time after completion of therapy of 24 months. Fourteen patients have relapsed (13) or progressed (1): ten in metastatic sites and four in the primary site. One patient had persistent local disease after radiation requiring amputation. Nine of the 13 patients with metastatic disease at diagnosis have relapsed compared with five of the 18 patients without metastatic disease. For the entire group, the actuarial survival is 78% (65% to 87%) at 30 months, and the actuarial disease-free survival is 58% (46% to 69%) at 30 months.

Adolescent↗
PubMed1987

Nucleotide sequence of the porcine transmissible gastroenteritis coronavirus matrix protein gene.

cDNA clones mapping within the first 2601 bases of the 3' end of the TGEV genome were sequenced completely or in part by the method of Maxam and Gilbert and open reading frames were examined. One reading frame yielding a protein having properties of the matrix (M) protein was identified. It is positioned at the immediate 5' side of the nucleocapsid (N) gene but is separated by an intergenic region of 12 bases. The deduced M protein is comprised of 262 amino acids, has a molecular weight of 29,544, is moderately hydrophobic, and has an amino acid sequence homology of approximately 36% with the mouse hepatitis coronavirus, 37% with the bovine enteric coronavirus, and 28% with the avian infectious bronchitis virus. Judging from an alignment with MHV and IBV proteins, the amino terminus of the TGEV M protein extends 54 amino acids from the virion envelope which compares with 26 for MHV and 21 for IBV.

Amino Acid Sequence↗
PubMed1987

High-dose oral and intravenous metoclopramide in doxorubicin/cyclophosphamide-induced emesis. A randomized double-blind study.

Emesis remains a major side effect of cancer chemotherapy. High-dose intravenous metoclopramide has proved to be effective antiemetic therapy for cisplatinum induced emesis. It has not been rigorously tested in nonplatinum chemotherapy. This double-blind, noncrossover, randomized trial compared high-dose oral and intravenous metoclopramide to standard oral prochlorperazine in emesis caused by doxorubicin [70 mg/m2 body surface area (BSA)] and cyclophosphamide (700 mg/m2 BSA). Prochlorperazine (10 mg/dose), oral metoclopramide, and intravenous metoclopramide (2 mg/kg/dose each) were given 30 min before chemotherapy and then every 4 h for 24 h. Ten patients were randomized to prochlorperazine therapy, 10 to oral metoclopramide, and 9 to i.v. metoclopramide. Median number of emeses for the first chemotherapy cycle was 3, 3, and 7 for prochlorperazine, oral, and i.v. metoclopramide, respectively. Statistical analysis showed no significant advantage of any regimen (p greater than 0.4). For patients who continued the antiemetic study, frequency of emesis increased with each successive cycle of chemotherapy. Six of 19 patients treated with metoclopramide developed dystonic reactions compared with zero of 10 on prochlorperazine. High plasma metoclopramide levels were achieved with both metoclopramide regimens and did not correlate with frequency of emesis. High-dose oral and i.v. metoclopramide in an every 4 h regimen did not show any advantage over standard antiemetic therapy for doxorubicin/cyclophosphamide-induced emesis and were associated with significant toxicity.

Administration, Oral↗
PubMed1987

Treatment of peripheral neuroepithelioma in children and young adults.

Seventeen patients with peripheral neuroepithelioma were treated with an intensive chemotherapy regimen of vincristine, Adriamycin (Adria Laboratories, Columbus, OH), and cyclophosphamide (VADRIAC) in combination with radiation therapy. Fifteen patients with stage III (seven) or stage IV (eight) at presentation were treated on a more intensive regimen including total body irradiation (TBI) (8 Gy). Two patients with stage I (one) or II (one) disease received a less intensive chemotherapy regimen of VADRIAC. Therapy was completed within 6 to 7 months in all patients. The disease arose in the chest wall in 12 patients, pelvis in three patients, and extremity in two patients. Sixteen of the 17 (94%) patients achieved a complete remission. With a median follow-up of 18 months, ten patients remain in complete remission with an actuarial survival of 68% and an actuarial relapse-free survival of 56% at 12 months. On the basis of our initial experience with this tumor, we believe that peripheral neuroepithelioma is a chemoresponsive and radioresponsive tumor.

Adolescent↗
PubMed1987

Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults.

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.

Adolescent↗
PubMed1987

Resident test ordering patterns.

Utilization of a selected set of laboratory tests in the ambulatory setting was determined for four classes of family practice residents over their entire three year training program. A total of nineteen residents were included in the study. Residents' test utilization in their third year of training was significantly lower than in their Post Graduate Year I (PGY I) and PGY II years. Though there was a substantial drop in residents' utilization between their first and second year, the drop was not significant. While most residents reduced their test utilization as they progressed through residency, several who were extremely low utilization in there first year of training actually increase test utilization in the second year. There was substantial variation in residents' test utilization, most marked in the first year but persisting for all three years. Although test utilization progressively fell through the three years of training, the residents who were high utilizers during their first year of training remained high utilizers for the remainder of their training. Though the variation in resident test utilization apparent in PGYI was maintained throughout residency, the degree of variation was reduced and greater uniformity was achieved as training progressed.

Clinical Laboratory Techniques↗