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Biomedical subjects

F E Johnson

Publications and source records attributed to F E Johnson.

At least 73 records · Page 4Linked to original sources

Buprenorphine differentially alters opioid receptor adaptation in rat brain regions.

Previous in vivo studies revealed that the mixed agonist-antagonist buprenorphine can down-regulate mu and up-regulate delta 2 and kappa 1 opioid receptors in rat brain. In this report brain regional differences in opioid receptor adaptation were addressed. Rats received i.p. injections with buprenorphine (0.5-2.5 mg/kg) and were killed 20 h later. Membranes from 7 brain regions were analyzed for mu (3H-[D-Ala2,N-mephe4,Gly-ol5] enkephalin), kappa 1 (3H-U-69593), delta 1 (3H-[D-Pen2, D-Pen5] enkephalin) and delta 2 (3H-deltorphin II) receptor binding parameters. Buprenorphine induced down-regulation of mu receptors in frontal cortex, occipital cortex, thalamus, hippocampus, striatum and brain stem. Kd values for 3H-[D-Ala2,N-mephe4,Gly-ol5] enkephalin were unchanged from controls. Up-regulation of kappa 1 receptors was observed in frontal, parietal, occipital cortexes and striatum. Binding to delta 2 sites was elevated in frontal and parietal cortexes. Buprenorphine did not alter delta 1 binding in any of the regions examined. Changes in opioid receptor adaptation induced by buprenorphine were further supported by data from cross-linking of 125I-beta-endorphin to cortical membrane preparations. A reduction in a 60- to 65-kDa band was detected in frontal and occipital cortices in which binding assays revealed down-regulation of mu receptors. In parietal cortex neither the 60- to 65-kDa product nor Bmax changes were observed. These results indicate that buprenorphine is a useful tool to study brain opioid receptor adaptation in vivo and the information accrued may be relevant to the mode of action of this drug in the treatment of heroin and cocaine abuse.

Adaptation, Physiological↗

How tumor stage affects surgeons' surveillance strategies after colon cancer surgery.

BACKGROUND: The factors that influence decision making among surgeons are not well understood. This study sought to evaluate how the tumor stage of patients subjected to potentially curative surgery for colon cancer affects the follow-up strategies used by practicing surgeons. METHODS: Hypothetical patient profiles and a detailed questionnaire based on these profiles were mailed to 2733 members of two major surgical societies. The effect of TNM Stage on the surveillance strategies chosen by the respondents was analyzed. RESULTS: Seven of the nine most commonly used surveillance modalities all were performed significantly more frequently with increasing TNM Stage. This effect persisted through 5 years of follow-up. The other two modalities (computed tomography and bone scan) were performed too infrequently for meaningful analysis. CONCLUSIONS: Surgeons performing surveillance after potentially curative surgery for otherwise healthy patients with colon cancer modify their strategies according to the patient's TNM Stage. These data should help in the design of prospective trials related to this topic.

Colonic Neoplasms↗

Cost of patient follow-up after potentially curative colorectal cancer treatment.

OBJECTIVE: To estimate the cost of follow-up among colorectal cancer patients treated with curative intent based on the broad spectrum of surveillance strategies suggested in the literature. DESIGN: Economic analysis of the costs associated with 11 separate surveillance strategies. Charge data were obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file. SETTING: Ambulatory care. MAIN OUTCOME MEASURES: Medicare-allowed charges and an actual-charge proxy for 5 years of follow-up after treatment for colorectal cancer patients on a nationwide basis. RESULTS: Medicare-allowed charges varied widely for the 5 years of posttreatment follow-up from a low of $561 to a high of $16,492. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $910 to $26,717, a 28-fold difference in charges. CONCLUSIONS: Charges vary extensively across follow-up strategies, with no indication that higher-cost strategies increase survival or quality of life.

Colorectal Neoplasms↗

Pancreatic cancer treatment in the U.S. veteran from 1987 to 1991: effect of tumor stage on survival.

To assess the outcomes after pancreatic cancer treatment in a nationwide hospital system, patients treated in Department of Veterans Affairs (DVA) hospitals from 1987 to 1991 were studied by tumor stage, the most significant reported influence on survival. Tumor registrars from DVA hospitals provided information that allowed TNM staging in 598 patients, and duration of survival from treatment to death was known in 96+% of cases. Survival was 9 months longer after 64 resections for stage I-II (localized) pancreatic cancer than after 149 other treatments (P < 0.05, ANOVA), but resection did not increase mean survival in 49 patients with stage III (lymph node metastases) disease. Twenty-one patients with ampullary, duodenal, bile duct, or cystic cancers had a significantly increased survival at any stage, but this may be due to the selection of sicker patients for nonoperative therapies.

Cholestasis↗

Surveillance after curative colon cancer resection: practice patterns of surgical subspecialists.

BACKGROUND: In the literature, suggested strategies for the follow-up of colon cancer patients after potentially curative resections vary widely. The optimal regimen to monitor for recurrences and new primary tumors remains unknown. The nationwide cost impact of wide practice variation is also unknown. METHODS: The 1,070 members of The Society of Surgical Oncology (SSO) were surveyed using a detailed questionnaire to measure the practice patterns of surgical experts nationwide. Respondents were asked how often they use nine separate methodologies in follow-up during years 1-5 postsurgery for TNM stage I, II, and III patients. Costs were estimated for representative less and more intensive strategies. RESULTS: Evaluable responses were received from 349 members (33%). Office visit and carcinoembryonic antigen analysis were performed most frequently. SSO members generally see patients every 3 months in years 1-2, every 6 months in years 3-4, and annually thereafter. There was wide variability in test ordering patterns and moderate variation between SSO and previously surveyed American Society of Colon and Rectal Surgeons members. The charge differential between representative less and more intensive follow-up strategies for each annual U.S. patient cohort is approximately $800 million. CONCLUSIONS: Actual practice patterns vary widely, indicating lack of consensus regarding optimal follow-up. The enormous cost differential associated with such variation is difficult to justify because there is no proven benefit of more intensive follow-up.

Colonic Neoplasms↗

Clinical surveillance testing after lung cancer operations.

BACKGROUND: Although routine clinical surveillance testing after lung cancer operation has important clinical implications for patients and financial implications for society, the ideal surveillance strategy is unknown. METHODS: We surveyed The Society of Thoracic Surgeons membership by questionnaire to characterize the current practice of follow-up among experts in lung cancer treatment. There were 2,009 responses (54% return) from the 3,700 members; 768 of those responding both operate on and provide long-term follow-up for lung cancer patients. These responses form the basis of this study. RESULTS: The follow-up methods most frequently used during a 5-year follow-up include clinic visit, chest roentgenography, complete blood cell count, liver function testing, and chest computed tomography. Sputum cytology, head computed tomography, bone scanning, chest magnetic resonance imaging, and bronchoscopy are used infrequently. Although there is wide variation in the frequency of use of these ten methods, there is significant (p < 0.05) decrease in the frequency of testing over time for all tests except sputum cytology and chest magnetic resonance imaging. The survey also requested information regarding motivation behind routine clinical surveillance testing. Although the presumed rationale for such follow-up includes probable clinical benefit for the patient, fewer than half of respondents believe that such surveillance testing would yield a survival benefit for either stage I (44% of respondents) or advanced-stage patients (17% of respondents) after lung cancer resection. Only 1 of 4 respondents believe that the current literature documents any survival benefit. Other reasons for follow-up include maintenance of rapport with colleagues or patients and medicolegal liability concerns. CONCLUSIONS: This survey provides direct evidence regarding current surveillance practice among thoracic surgeons. There appears to be marked variation among members of The Society of Thoracic Surgeons in frequency of and rationale for routine clinical surveillance testing.

Adult↗

Small bowel melanoma: extended survival with surgical management.

Small intestinal melanoma is rare, and primary vs metastatic origin is often unclear. A patient with the longest reported survival (21 years) after resection of a melanoma in the small intestine is presented, and the debate regarding primary small bowel melanoma is reviewed. Multiple resections of neck recurrence (or second primaries) in this patient with prolonged survival validates the aggressive pursuit and excision of localized melanoma when possible.

Adult↗

Evaluation of alternate messages on an electronic message strip to recruit subjects to a smoking-cessation program.

The authors previously published details of a method to evaluate the effectiveness of electronic message strips in recruiting subjects to a smoking-cessation program. They now report data suggesting that a shorter, more negative message yields better results than a longer, more positive message. The data also show that this approach increases the number of subjects who enroll in a smoking-cessation program and the number of subjects who actually quit smoking.

Adult↗

Cisapride for constipation in spinal cord injured patients: a preliminary report.

Chronic constipation in patients with spinal cord injury (SCI) has significant impact on quality of life. To measure baseline clinical functioning, colonic transit time and anorectal manometry and the effect of cisapride on these clinical and physiological parameters, we studied 12 SCI patients. Patients initially received baseline clinical scoring, measurement of colonic transit time and anorectal manometry. Patients then received cisapride 20 mg orally three times each day. After one and three months of cisapride therapy, all measurements were repeated. The mean duration cisapride treatment was 5.2 months. Six of 12 (50 percent) reported that symptoms of constipation improved. No patient had worsening of symptoms. Prior to cisapride treatment, 23 percent of patients passed colonic transit markers by day five and 57 percent by day seven; baseline anal manometry revealed variable resting and squeeze pressures. After treatment, 33 percent of patients passed their colonic transit markers by day five and 71 percent by day seven. Six of 12 (50 percent) demonstrated a 10 percent or more increase in resting anal canal pressures. We conclude that about 50 percent of SCI patients have subjective improvement in constipation after cisapride therapy. Cisapride appears to improve both colonic and anorectal function.

Cisapride↗

The Whipple resection for cancer in U.S. Department of Veterans Affairs Hospitals.

OBJECTIVE: The authors compiled the results after Whipple resection for cancer from a large U.S. national hospital system. METHODS: Computerized hospital and death benefits records for patients treated with Whipple resection for cancer from 1987 to 1991 in U.S. Department of Veterans Affairs hospitals were analyzed, excluding lymphomas and neuroendocrine tumors. Institutional tumor registrar reports allowed TNM staging in 45% of these cancers. RESULTS: Whipple resections were performed in 252 patients with pancreatic cancer and 117 with other periampullary cancers. Complications occurred in 37%, and 30-day operative mortality was 8%. Postoperative sepsis was associated with a higher operative mortality rate. In patients with staged tumors, 5-year survivors were found only in those without lymph node involvement. CONCLUSIONS: Whipple resection can cure cancer in or near the head of the pancreas when lymph nodes are not invaded by tumor. Complications occur in nearly 40% of patients, whereas operative mortality rate is related to the average age of the patient population.

Adenocarcinoma↗

Post-treatment management options for patients with lung cancer.

OBJECTIVES: The first objective was to identify variations in patient management practice patterns after potentially curative lung cancer surgery. Patient management practice patterns were expected to range from intensive follow-up to no active surveillance. The second objective was to measure whether intensity of follow-up was related to patient outcomes. METHODS: An 18-month retrospective analysis was conducted of 182 patients with low TNM stage (< or = IIIA) lung cancer who were surgically treated with curative intent over the 11-year period from 1982 through 1992 at the St. Louis Department of Veterans Affairs Medical Center. RESULTS: Patients were followed for a mean of 3.3 years, until death or the end of the study. Analyses of diagnostic test and outpatient visit frequency distributions and cluster analyses facilitated the identification of 62 nonintensively followed patients and 120 intensively followed patients. Both groups were comparable at baseline, and there were no significant differences in patient outcomes attributable to intensity of follow-up. Intensively followed patients did, however, live an average of 192 days longer than nonintensively followed patients. CONCLUSIONS: Significant variations in follow-up practice patterns can exist within a single health care facility. In this analysis, variations in test and visit frequency did not result in statistically significant differences in patient outcomes, though the survival difference between groups suggests that some benefit might exist. Only well-designed prospective trials are likely to answer the question of what constitutes optimal follow-up after potentially curative lung cancer treatment.

Case-Control Studies↗

Rare anal canal cancers in the U.S. veteran: patterns of disease and results of treatment.

Nationwide treatment results among U.S. veterans with rare anal cancers (AC) have not been previously reported. We sought to evaluate the demographics and treatment outcome of patients with rare AC in Veterans Affairs Medical Centers (VAMCs). Using national VA computer data sets, we identified all patients with the ICD-9 diagnostic code (154.2) for anal cancer from 1987-1991. Patient demographics, histopathology, tumor size, results of treatment, and survival data were sought from local tumor registrars. A total of 405 patients with AC were identified by computer search; 204 (51%) were evaluable. 164 (80%) had squamous cell carcinomas, 25 (13%) had basaloid carcinomas, 8 (4%) had melanomas and 7 (3%) had anal gland adenocarcinomas. Patients were treated either by local excision, abdominoperineal resection (APR), or primary chemoradiation. Mean follow-up was 5.1 years. Among 25 patients with basaloid tumors, 19/25 were treated with chemoradiation; 13/19 (68%) are alive, and 3/5 treated with radical surgery are living. Among the seven patients with adenocarcinoma, those treated with CR fared better than those who underwent APR. Among the 8 patients with melanoma, 3/7 (38%) underwent primary APR, and 5 (62%) were treated by local excision; 7/8 died. Rare anal tumors account for 20 per cent of all anal canal cancers in the VA population. Patients with basaloid tumors respond well to chemoradiation. Patients with anal melanoma continue to have a poor prognosis.

Adenocarcinoma↗

Recent experience with cancer of the ampulla of Vater in a national hospital group.

A total of 64 resections, 24 operative bypasses and 35 nonoperative biliary intubations, were performed for ampullary carcinoma in U.S. Dept. of Veterans Affairs hospitals from 1987 to 1991. Mean survival after resection was 702 days, significantly higher (ANOVA, P < or = 0.005) than that after bypass (345 days) or intubation (385 days). Operative mortality rates were similar: resection or intubation = 14%, bypass = 12%. Operative (30-day) mortality was zero in four local resections, 10% in 51 Whipples and 44% in nine total pancreatectomies. TNM staging was available for 74 patients, and mean survival after resection exceeded 2 years in 34 patients with Stage I-II (localized) cancers, was 532 days in 10 patients with Stage III (regional nodes +) and 77 days in two patients with Stage IV (metastatic) disease. However, mean survival without resection was 498 days in 14 patients with localized cancer, 634 days in two patients with regional and 215 days in 11 patients with distant metastases. Resection clearly increased survival only for Stage I cancers (P < or = 0.02). Predicted 5-year survival rates by stage after resection were: I-II = 21%, III < 10%, IV = 0%. Complications were recorded in 29 per cent of resected patients, with sepsis the most common (21% of resections). Both sepsis and GI bleeding significantly decreased mean survival (P < or = 0.05, ANOVA), but pneumonia, pancreatic fistula, or wound problems did not. Ampullary cancer is a favorable subtype of peri-ampullary cancers, but prolonged survival is also seen without resection and may be largely limited to tumors that do not involve regional nodes.

Adenocarcinoma↗

Distal pancreatectomy for cancer: results in U.S. Department of Veterans Affairs hospitals, 1987-1991.

Although cancers of the pancreatic body and tail are often advanced at the time of diagnosis, resection of localized tumors can result in long-term survival. A search of the computerized records of the U.S. Department of Veterans Affairs (DVA) revealed 29 distal pancreatectomies performed for pancreatic cancer from 1987 to 1991. Operative complications and survival data were available on all patients, and pathologic and staging information were retrieved on 21 patients, seven of whom had cancers other than pancreatic adenocarcinoma. Although 30-day mortality was high after distal pancreatectomy (21%), mean survival exceeded 1 year for patients with localized pancreatic adenocarcinoma and for those with histologies other than pancreatic cancer. Surgical resection should be offered to patients with lesions of the pancreatic body and tail when metastases are not demonstrated; survival will likely be prolonged when nodal or systemic metastases are absent. These recent DVA results from a wide variety of surgeons, hospital sizes, and university affiliations may more closely reflect the national experience with this operation in patients with cancer than do single institutional reports.

Humans↗

A monoclonal anti-idiotypic antibody to opioid receptors labels desipramine-induced opioid binding sites on rat C6 glioma cells and attenuates thymidine incorporation into DNA.

Treatment of rat C6 glioma cells with the tricyclic antidepressant desipramine induces opioid binding. Here the distribution of these opioid-binding sites on C6 cell membranes and a functional property were investigated. Immunohistochemical examination of C6 cells was performed using a monoclonal anti-idiotypic antibody to opioid receptors (Ab2AOR). Ab2AOR uniformly labeled > 97% of the cells exposed to desipramine over their entire surface. The opioid-receptor antagonist naltrexone completely blocked Ab2AOR binding. Ab2AOR, which has opioid agonist properties, also inhibited DNA synthesis in desipramine-treated but not in naive C6 cells. Similarly, morphine blocked C6 cell proliferation only after desipramine treatment. The antineurotrophic action of Ab2AOR was reversed by naltrexone and was insensitive to pertussis toxin. These findings demonstrate that Ab2AOR suppresses the proliferation of C6 glioma cells by binding to desipramine-induced opioid receptors.

Animals↗

Testicular cytotoxicity of intravenous methotrexate in rats.

Although the testicular cytotoxicity of methotrexate has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of methotrexate (0-700 mg/kg body weight [BW]), with necropsy 56 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, modified Johnsen score, repopulation index, and epididymal index. Effects of methotrexate on heart, lung, liver, and kidney histology were evaluated qualitatively. Oligospermia occurred at low and intermediate dosages of methotrexate, but testicular atrophy was not observed. LD50 at day five for methotrexate appears to be approximately 300 mg/kg BW using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.

Animals↗

Current follow-up strategies after resection of colon cancer. Results of a survey of members of the American Society of Colon and Rectal Surgeons.

UNLABELLED: The follow-up of patients after potentially curative resection of colon cancer has important clinical and financial implications for patients and society, yet the ideal surveillance strategy is unknown. PURPOSE: The aim of this study was to determine the current follow-up practice pattern of a large, diverse group of experts. METHODS: The 1,663 members of The American Society of Colon and Rectal Surgeons were asked, via a detailed questionnaire, how often they request nine discrete follow-up evaluations in their patients treated for cure with TNM Stage I, II, or III colon cancer over the first five posttreatment years. These evaluations were clinic visit, complete blood count, liver function tests, serum carcinoembryonic antigen (CEA) level, chest x-ray, bone scan, computerized tomographic scan, colonoscopy, and sigmoidoscopy. RESULTS: Forty-six percent (757/1663) completed the survey and 39 percent (646/1663) provided evaluable data. The results indicate that members of The American Society of Colon and Rectal Surgeons generally conduct follow-up on their patients personally after performing colon cancer surgery (rather than sending them back to their referral source). Routine clinic visits and CEA levels are the most frequently performed items for each of the five years. The large majority (> 75 percent) of surgeons see their patients every 3 to 6 months for years 1 and 2, then every 6 to 12 months for years 3, 4, and 5. Approximately 80 percent of respondents obtain CEA levels every 3 to 6 months for years 1, 2, and 3, and every 6 to 12 months for years 4 and 5. Colonoscopy is performed annually by 46 to 70 percent of respondents, depending on year. A chest x-ray is obtained yearly by 46 to 56 percent, depending on year. The majority of the members of The American Society of Colon and Rectal Surgeons do not routinely request computerized tomographic scan or bone scan at any time. There is great variation in the pattern of use of complete blood count and liver function tests. Members of The American Society of Colon and Rectal Surgeons from the United States tend to follow their patients more closely than do those living in other countries. The intensity of follow-up does not markedly vary across TNM Stages I to III. CONCLUSION: The surveillance strategies reported here rely most heavily on clinic visits and CEA level determinations, generally reflecting guidelines previously proposed in the current literature.

Appointments and Schedules↗