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Biomedical subjects

F E Johnson

Publications and source records attributed to F E Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Pancreatic cancer palliation: using tumor stage to select appropriate operation.

To assess the effect of tumor stage on the surgical palliation of pancreatic cancer, 350 cancers from 74 U.S. Department of Veterans Affairs (DVA) hospitals from 1987 to 1991 were staged from pathologic and operative data, then grouped by initial surgery: biliary bypass only (BO), gastric bypass only (GO), or combined biliary and gastric bypass (BG). Re-operations were recorded as later gastric and/or biliary bypass: Stages I-II (local disease): BO (n = 52)--6 later gastric (12%), 3 later biliary (6%); BG (n = 60)--3 later gastric (5%); 3 later biliary (5%). Stage III (positive nodes): BO (n = 26)--1 later gastric (4%); BG (n = 35)--1 later gastrobiliary bypass (3%). Stage IV (metastases): BO (n = 71)--3 later gastric (4%), 3 later biliary (4%); BG (n = 70)--2 later gastrobiliary bypass (3%). GO (all stages): (n = 41)--1 later gastric (2%), 4 later biliary (10%). Using a two-factor ANOVA comparing survival by stage and original surgery, we found that stage had a significant effect on survival (p = 0.0001), but the type of initial bypass operation had no effect. Re-operation after palliative pancreatic cancer surgery was necessary in less than 5% of patients with BG. Initial BG reduced the incidence of re-operation for patients with jaundice and without metastatic disease, and may also benefit patients with gastric obstruction alone. Patients with jaundice who have peritoneal or liver metastases can be treated effectively with BO if they have no symptoms of gastric outlet obstruction.

Adenocarcinoma↗
PubMed1994

A reappraisal of total pancreatectomy for pancreatic cancer: results from U.S. Veterans Affairs hospitals, 1987-1991.

BACKGROUND: After enthusiasm for total pancreatectomy for pancreatic adenocarcinoma peaked in the 1970s, a failure to improve outcomes in the 1980s led to fewer reports of this procedure. METHODS: We retrieved records from 252 Whipple and 47 total pancreatectomies for pancreatic cancer performed at U.S. Department of Veterans Affairs hospitals from 1987 to 1991. RESULTS: Thirty-day mortality was 8% with both procedures. There was no significant difference in morbidity at 30 days (Whipple 36%, total pancreatectomy 39%). The mean survival after total pancreatectomy was 526 days compared to 376 days following Whipple (P = 0.03). Staging information was retrieved from tumor registrars for 117 patients with pancreatic adenocarcinoma, 21 of whom underwent total pancreatectomy and 96 the Whipple procedure. In patients with stage I and stage II localized pancreatic adenocarcinoma, mean survival was 772 days in 11 patients after total pancreatectomy, and 446 days in 55 patients after Whipple resection (P = 0.057). CONCLUSION: The type of resection did not affect the mean survival of patients with stage III (nodal metastases) or stage IV (distant metastases) cancer.

Adenocarcinoma↗
PubMed1994

In vitro and in vivo expression of opioid and sigma receptors in rat C6 glioma and mouse N18TG2 neuroblastoma cells.

Mouse N18TG2 neuroblastoma and rat C6 glioma cell lines were injected into male nude mice, and the tumors were passaged serially. At each generation, tumors were analyzed for delta opioid binding using [3H][D-Ala2,D-Leu5]enkephalin and for sigma 1 and sigma 2 binding with 1,3-[3H]di-o-tolylguanidine in the presence and absence of 1 microM pentazocine. Receptor density (Bmax) and affinity (KD) were estimated by homologous competition binding assays. Opioid and sigma Bmax values in the solid tumors were significantly lower than their original levels in vitro. KD values for opioid/sigma ligands were similar in vitro and in vivo. With successive passages in the murine host, delta opioid and sigma 1 binding of the neuroblastoma-derived solid tumors became undetectable. In contrast, sigma 2 receptor Bmax values were unchanged with successive passages of the neuroblastoma-derived tumors and doubled in the nude mouse-borne gliomas. When neuroblastoma-derived solid tumors that were devoid of delta opioid binding were returned to culture, opioid receptors appeared to be up-regulated as compared with their original in vitro levels. Serial passaging of these recultured cells in vivo again resulted in a rapid decline in opioid receptor content. The opioid data are consistent with our prior findings on opioid binding diminution in human brain tumors. The pattern of change for sigma binding was more complex, with the sigma 2 response in late passages of the glioma being reminiscent of the formerly observed increase in number of sigma sites in transformed human meninges, kidney, and colon tissue.

Animals↗
PubMed1994

Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy.

OBJECTIVE: The outcomes of patients with squamous cell carcinoma of the anal canal treated by either sphincter-preserving procedures or radical surgery were evaluated, with the goals of identifying factors predicting treatment failure and quantifying results of salvage therapy in patients with recurrent disease. BASIC PROCEDURES: A population-based study on all patients in all 159 hospitals of the Department of Veterans Affairs (VA) from 1987 to 1991 was carried out. Data were compiled from several national computerized VA data sets. Supplementary information from local tumor registrars also was obtained, including demographic information, discharge summaries, operative reports, pathology reports, and medical oncology and radiation oncology summaries. From these sources, information on tumor histology, tumor stage, tumor grade, presence of regional or distant metastases, surgical procedures, use of chemotherapy and radiation therapy (RT), toxicity of chemotherapy and RT, development of recurrent disease, treatment of recurrence, survival, and cause of death were obtained. MAIN FINDINGS: Four hundred five patients with anal cancer were identified by computer search, and 204 (51%) were evaluable; 164 of 204 (80%) had squamous cell carcinoma, 137 of whom (84%) were treated with sphincter-preserving procedures, and 27 of whom (16%) were treated by by radical surgery. One hundred fourteen of 138 (83%) were treated by multimodality therapy, which we defined as local excision followed by chemotherapy and RT. The mean dose of RT among patients treated by multimodality therapy was 4200 +/- 540 cGy and 82% of those treated with multimodality therapy received 5-FU/mitomycin C. Recurrent disease was diagnosed in 43 of all 149 patients (29%) with potentially curable disease. (stages I-III) Multivariate analysis revealed that stage at diagnosis (p = 0.04) and method of treatment (p = 0.03) were the sole predictors of recurrence. Fifty-three percent of patients who underwent salvage abdominoperineal resection (APR) are alive, whereas only 19% who underwent salvage chemotherapy with or without RT are alive. PRINCIPAL CONCLUSIONS: These data indicate that multimodality therapy currently is being employed in the majority of patients with squamous cell carcinoma of the anal canal in the VA system. Tumor stage and method of treatment appear to affect the likelihood of development of recurrent disease. Salvage APR has curative potential. Results with salvage chemotherapy and RT are disappointing.

Aged↗
PubMed1994

Connecting the health sciences community to the Internet: the NLM/NSF grant program.

In 1992, as part of its high-performance computing and communications initiative, the National Library of Medicine decided to provide health sciences institutions with Internet connection grants similar to those offered to universities by the National Science Foundation. Although library involvement is not required, librarian and library uses have been the most common category in the applications received.

Computer Communication Networks↗
PubMed1994

Opioids inhibit endothelin-mediated DNA synthesis, phosphoinositide turnover, and Ca2+ mobilization in rat C6 glioma cells.

Opioid agonists inhibit DNA synthesis in C6 rat glioma cells that express opioid receptors, induced by desipramine (DMI). This inhibition was not observed in cells that were not treated with DMI, and thus did not express opioid-binding sites. Endothelin, a known mitogen, increased thymidine incorporation dose dependently (up to 1.7-fold) in DMI-treated C6 cells. This increase was reversed by an anti-idiotypic antibody to opioid receptors, Ab2AOR, which has opioid agonist properties. The opioid antagonist naltrexone blocked the inhibition caused by Ab2AOR. Endothelin also stimulated phosphoinositide (PI) turnover and this effect was inhibited by morphine (50%) or by Ab2AOR (72%) in DMI-treated but not in DMI-untreated C6 cells. These actions of morphine and Ab2AOR were reversed by naltrexone. The inhibition of PI turnover and of thymidine incorporation by Ab2AOR or morphine was insensitive to pertussis toxin (PTX). Since PI turnover is known to induce Ca2+ mobilization, it was of interest to examine the effects of the applied opioids on intracellular Ca2+ concentrations. Endothelin increased the concentration of cytosolic free Ca2+ in the cells while Ab2AOR, morphine, and beta-endorphin reversed the endothelin-induced Ca2+ mobilization in DMI-treated but not in DMI-untreated C6 cells. The effect of these agonists was also blocked by naltrexone. The results indicate that glial cells can be a target of an opioid receptor-mediated antimitogenic action and that an abatement in PI turnover and Ca2+ mobilization may be associated with this mechanism.

Animals↗
PubMed1994

Periampullary cancer treatment in U.S. Department of Veterans Affairs hospitals: 1987-1991.

BACKGROUND: Reported treatment outcomes for painless jaundice caused by ampullary, distal biliary, or duodenal (ABD) cancer are better than those caused by pancreatic cancer. METHODS: Outcomes after resection, bypass, or biliary intubation were compared in 432 patients with ABD cancer and 1753 with periampullary pancreatic cancer from U.S. Veterans Affairs hospitals. Computer and tumor registrar records from 1987 to 1991 were compiled; follow-up to death was complete in more than 93%. RESULTS: Operative mortality and complication rates were similar for each diagnosis. Adenocarcinomas staged from registrar reports (179 ABD, 571 pancreatic) exhibited significantly longer mean survival time (analysis of variance; p < or = 0.03) in patients with ABD for all stage groupings (localized, node involvement, metastatic) when stratified by treatment. After localized cancer resection, projected 5-year survival rate was 30% in 58 patients with ABD and 6% in 64 with pancreatic cancer. However, mean survival rates were similar with or without resection when nodes were involved. No 5-year survivors were projected after resection with nodal or distant metastases. CONCLUSIONS: Patients with ABD had a longer mean survival time than those with pancreatic adenocarcinoma, and this difference persisted when studied by TNM stage. The curative potential of resection was confined to patients without nodal involvement.

Adenocarcinoma↗
PubMed1994

Complications and outcomes in the treatment of pancreatic adenocarcinoma in the United States veteran.

BACKGROUND: Treatments for carcinomma of the pancreas have wide variations in reported complications and results. STUDY DESIGN: A population-based retrospective analysis of invasive treatments for carcinoma of the pancreas in all United States Department of Veterans Affairs hospitals was conducted using computerized patients files from 1987 to 1991. RESULTS: One thousand nine hundred sixty-four patients (99 percent male) were classified by the most aggressive treatment: 327 patients had pancreatic resections, while 1,180 had operative biliary or gastric bypasses, and 457 had percutaneous or endoscopic biliary intubations. Resection was associated with the lowest 30-day mortality rate (12 percent) and the longest mean survival period (449 days), but also the highest complication rate (37 percent) and mean period of hospitalization (53 days), with a projected five-year survival rate of 12 percent. After operative bypass, the 30-day mortality rate was 19 percent and the mean survival period was 234 days. Corresponding values after nonoperative biliary intubation were 32 percent and 223 days. Results were independent of hospital size and university affiliation, but were poorer in patients more than 60 years of age. CONCLUSIONS: This national series of therapy for carcinoma of the pancreas demonstrates that resection yielded a significantly longer survival period, with a lower mortality rate than other treatments. The results were consistent across categories of hospital size or university affiliation.

Adenocarcinoma↗
PubMed1993

Testicular circulatory isolation in man: comparison of radionuclide angiography with Doppler evaluation.

Testicular circulatory isolation (TCI) holds promise as a method to avoid drug-induced infertility in male patients about to receive cancer chemotherapy. Complete exclusion of blood flow to the testicle is essential to the success of this technique. We have compared the hand-held Doppler probe and radionuclide angiography (technetium-99m pertechnetate) as monitors of testicular blood flow in 10 patients subjected to unilateral TCI. When Doppler evaluation indicated that testicular circulation had been interrupted, the radionuclide angiogram uniformly confirmed and quantified this conclusion. These results validate the hand-held Doppler as an appropriate tool for assessing testicular blood flow in patients undergoing TCI.

Aged↗
PubMed1993

Testicular cytotoxicity of intravenous procarbazine in rats.

Although the testicular cytotoxicity of procarbazine 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 procarbazine (0-700 mg kg body weight), with necropsy 59 +/- 2 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. Effects of procarbazine on heart, lung, liver and kidney histology were evaluated qualitatively. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of procarbazine. Marked testicular atrophy, oligospermia and germinal hypoplasia were observed at high dosages (500 and 700 mg kg-1 body weight). LD50 at day 59 for procarbazine appears to be approximately 600 mg kg-1 body weight using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.

Animals↗
PubMed1993

Regional procarbazine delivery reduces testicular toxicity.

Procarbazine has been implicated as a cause of infertility. Regionalization of drug delivery is a potential method to avoid this problem. We investigated the protective effect of testicular circulatory isolation (TCI) on gonadal toxicity during procarbazine administration in the Sprague-Dawley rat. Four groups (n = 10/group) were used. Animals in group 1 received no treatment. Rats in groups 2 and 3 were anaesthetized and received TCI of the left testis by clamping of the spermatic cord and gubernaculum immediately before a bolus of intravenous procarbazine (400 mg kg-1). The clamping was maintained for 15 min after procarbazine administration in group 2 and for 45 min in group 3. Rats in group 4 received sham surgery immediately before procarbazine administration. On day 70, all rats were killed and necropsied. Testicular toxicity was evaluated qualitatively by histology and quantitatively by measurements of testicular weight, sperm head count, repopulation index, and epididymal index. The results indicated that 15 min of TCI did not mitigate testicular toxicity; 45 min of TCI provided moderate protection against procarbazine-induced testicular toxicity.

Animals↗
PubMed1993

Palliative operations for pancreatic cancer in the hospitals of the U.S. Department of Veterans Affairs from 1987 to 1991.

A total of 1,180 patients underwent palliative surgery for pancreatic cancer in the 158 hospitals of the U.S. Department of Veterans Affairs from 1987 to 1991. Using computerized data files, we analyzed these procedures according to type of procedure (gastric bypass only [GO], biliary bypass only [BO], or combined biliary and gastric bypass [BG]), survival, reoperation and complication rates, patient age, and operative (30-day) mortality. Survival after GO (208 days) was significantly shorter than after BO or BG (279 days and 259 days, respectively; p < or = 0.05 by analysis of variance). The reoperation rate after BO (12%) was higher than after BG (5%; p < or = 0.001 by chi 2 analysis) and was due to the higher incidence of reoperative gastric bypass in the BO group. Complication rates were similar after all bypass types. Reoperations had a 25% 30-day mortality. The 32 gastric bypasses performed after an initial BO were done at a mean of 193 days after the original BO bypass, whereas other reoperations were undertaken at a mean of 73 days after the first operation. This first national study of palliative operations for pancreatic cancer supports combined biliary/gastric bypass as the initial procedure, thus minimizing reoperations and their attendant morbidity.

Aged↗
PubMed1993

Evaluation of an electronic message strip to recruit smokers to a smoking cessation program.

Knowledge of outcome is essential when analyzing effectiveness of educational programs. Although quantitative data can be analyzed more rigorously than other forms of data, quantitation of behavioral processes is often difficult. To promote our smoking-cessation program we designed a method that relies on electronic message strips and a dedicated telephone line capable of providing quantitative outcome information. This approach appears quite versatile and shows that the electronic message strip is a surprisingly ineffective method of enlisting subjects into a smoking-cessation program in our hospital.

Equipment Design↗
PubMed1993

Distribution and metabolism of pentoxifylline in non-tumor-bearing mice.

Pentoxifylline increases tissue oxygen delivery in patients with atherosclerotic arterial disease by several mechanisms, including lowering blood viscosity and increasing erythrocyte flexibility. Since tumor neo-vessels are also abnormal and associated with intra-tumoral hypoxia and, thus, with radiation failure, pentoxifylline might also be useful as a radiation sensitizer. The mouse is frequently used to study such drugs, but the pharmacokinetics of pentoxifylline in the mouse have not been determined. We investigated this in three separate experiments by administering pentoxifylline intraperitoneally, subcutaneously, or orally. Plasma was assayed for the parent drug and its metabolites by capillary gas chromatography. High plasma levels of pentoxifylline and both major derivatives occurred within several minutes after intraperitoneal or subcutaneous injection, but plasma levels were low after oral administration.

Administration, Oral↗
PubMed1993

Serum levels of pentoxifylline and its metabolites in non-tumor-bearing mice after chronic oral pentoxifylline administration.

Pentoxifylline lowers blood viscosity and increases erythrocyte flexibility in patients with atherosclerosis, thus increasing tissue oxygen delivery. Since tumor neo-vessels are associated with tissue hypoxia, which contributes to failure of radiation therapy, pentoxifylline might also be useful as a radiation sensitizer. Such drugs are often evaluated in the murine model, but serum levels of pentoxifylline and its metabolites have not been determined in the mouse after chronic oral dosing. We investigated this by administering pentoxifylline via liquid diet or solid diet to young adult male CF1 mice for one to six weeks and assaying plasma for the parent drug and its metabolites. At one, three, and six weeks, plasma levels of pentoxifylline and major derivatives were consistently detectable. Mice remained healthy during this period, indicating that ingestion of large amounts of this drug is well tolerated.

Administration, Oral↗
PubMed1992

Small cell undifferentiated carcinoma of the pancreas. Report of a patient with tumor marker studies.

BACKGROUND: Small cell undifferentiated carcinoma of the pancreas is a rare type of pancreatic neoplasm. METHODS: The authors report the clinical and pathologic aspects of a patient with this malignant lesion and an extensive serologic and immunohistochemical survey of potential ectopically produced hormones or tumor markers. RESULTS: Neuron-specific enolase (NSE) emerged as a tumor marker. CONCLUSIONS: NSE could be valuable in the diagnosis and management of other patients with this rare disease.

Biomarkers, Tumor↗
PubMed1992

Posthemipelvectomy hernia.

We present four patients who developed posthemipelvectomy hernias. Identified etiologic factors include infection at the time of hemipelvectomy, radiation therapy, and excessive weight gain. Two patients were reconstructed using local tissues, and two required prosthetic materials. There were no hernia recurrences, although two patients died of recurrent cancer.

Adult↗