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Biomedical subjects

R Wesley

Publications and source records attributed to R Wesley.

At least 19 recordsLinked to original sources
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↗
PubMed1986

Adverse prognostic influence of hepatitis B virus infection in acute lymphoblastic leukemia.

Liver function test abnormalities were examined in a retrospective survey in a population of 90 children with acute lymphoblastic leukemia (ALL) treated in a similar fashion with therapy, using primarily methotrexate, mercaptopurine, vincristine, and prednisone. A twofold or greater elevation of serum glutamyl pyruvic transaminase (SGPT) was found in 80% of the patients during induction therapy, in 63% of the patients during maintenance therapy, and 31% of the patients who completed therapy. Circulating hepatitis B virus surface antigen (HBsAg) was noted in 26% of patients with liver function test abnormalities during maintenance therapy, and 45% of patients with liver function test abnormalities after the completion of therapy. Hepatitis B virus infection was therefore, the most important single cause of abnormal liver function during remission in our patient population. Though others have asserted that hepatitis B virus infection is relatively benign in immunosuppressed individuals, in our population, this agent often caused severe pathological and clinical sequelae. This may be related to the high frequency (50%) of co-infection with the delta agent in our HBsAg-positive patients. Furthermore, hepatitis B virus surface antigenemia conferred an adverse prognostic influence for these children in terms of their leukemia-free survival.

Acute Disease↗
PubMed1986

5-Fluorouracil chemotherapy and pelvic radiation in the treatment of large bowel cancer. Decreased toxicity in combined treatment with 5-fluorouracil administration through the intraperitoneal route.

Multimodality cancer therapy commonly involves the interactions of surgeon, radiation therapist, and medical oncologist. This prospective study was undertaken to record possible adverse effects of surgery, external beam radiation therapy, and 5-fluorouracil (5-FU) chemotherapy in the treatment of large bowel cancer. The dose of 5-FU by the intraperitoneal (IP) or intravenous (IV) routes was diminished when pelvic radiation therapy was given. The reduction in drug dose that was required was much greater when 5-FU was given IV as compared to IP. The proportion of patients remaining on IV 5-FU chemotherapy was significantly reduced when the patient received pelvic radiation. There was a significant increase in leukopenia and thrombocytopenia when patients received pelvic radiation. Hematologic toxicity was more severe when there was IV compared with IP administration of 5-FU. Pelvic radiation therapy diminished the patient's capacity to receive chemotherapy because of hematologic toxicity. The locoregional administration of 5-FU chemotherapy was better tolerated as part of a multimodality treatment regimen than was systemic administration.

Clinical Trials as Topic↗
PubMed1986

High-grade soft tissue sarcomas of the extremities.

From July 1975 to December 1982, 358 patients were referred to the Surgery Branch of the National Cancer Institute (NCI) with the diagnosis of soft tissue sarcoma of the extremities. Two hundred eleven of these patients presented with resectable, localized high-grade soft-tissue sarcomas and have been included in the present analysis of the management and outcome of patients with high-grade soft tissue sarcomas of the extremity treated at the NCI. One hundred forty-seven of these 211 patients have been included in randomized prospective trials. The remaining 64 patients in this analysis have been followed at the NCI, but were not included in randomized trials because of patient refusal or ineligibility. Tumor size was identified as a highly significant prognostic variable for disease-free and overall survival (P2 = 0.00001 and 0.0081, respectively). Tumor site, histologic type, and microscopic margins of resection were not significant prognostic variables. There was no difference between patients undergoing amputation compared to those undergoing limb-sparing procedures plus postoperative radiotherapy in disease-free or overall survival for all 211 patients in this study (P2 = 0.068 and 0.131, respectively). A significantly greater frequency of local failure among patients treated by local excision was noted compared to patients undergoing amputation (12/128 versus 0/83, P2 = 0.004), but this did not result in decreased overall survival in patients undergoing combined modality limb-sparing procedures. Adjuvant chemotherapy significantly prolonged disease-free survival (P2 = 0.005) for the 124/211 patients treated with adjuvant chemotherapy, although analysis of overall survival did not reveal a significant increase (P2 = 0.10). In a subset of 65 patients included in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy, a significant improvement in both disease-free (P2 = 0.033) and overall (P2 = 0.055) survival was seen in patients receiving chemotherapy. Sixty-five patients developed recurrent disease (65/211, 31%) and 42 of these patients were rendered disease-free surgically. Survival from the time of first recurrence was significantly prolonged among the 42 patients who were rendered disease-free (median survival, 31 months) compared to those who were not (median survival, 9 months, P2 less than 0.001).

Actuarial Analysis↗