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Biomedical subjects

J A Butler

Publications and source records attributed to J A Butler.

At least 73 records · Page 4Linked to original sources

Metabolism of selenite and selenomethionine in the rhesus monkey.

Female rhesus monkeys were fed a commercial monkey diet and given selenium (Se) as either selenite or selenomethionine (SeMet) in the drinking water for 11 mo. Muscle and liver biopsies were taken initially and at the end of the experiment for determination of Se levels and glutathione peroxidase (GPX) activity. Blood was collected at monthly to bimonthly intervals, and the plasma and erythrocytes were subjected to gel filtration to determine the distribution of Se among proteins of various molecular weights. At the end of the experiment, there was significantly more Se in liver, muscle and hair from the monkeys given SeMet than in tissues from those given selenite, but there were no differences in liver or muscle GPX activity between the two treatment groups. The erythrocyte and plasma Se levels were significantly higher in the monkeys given SeMet than in those receiving selenite, but there were no differences in the GPX levels between these groups. About 68% of erythrocyte Se was associated with GPX in monkeys given selenite whereas only 34% was associated with GPX in those administered SeMet. The correlation coefficient for blood Se level and erythrocyte GPX activity was 0.92 in monkeys given selenite but only 0.37 in those given SeMet. Gel filtration of plasma revealed only one Se peak for plasma from the monkeys given selenite but at least two major Se peaks for plasma from monkeys receiving SeMet. The possible implications of these results for humans are discussed, including the reasons for poor correlations of GPX activity and blood Se levels.

Animals↗

Palliation for nonpancreatic malignant obstruction of the biliary tract.

To determine the best palliation for nonpancreatic malignant obstruction of the biliary tract, we analyzed 36 patients with unresectable tumors who were treated from 1970 to 1986. Eleven men and 25 women were treated for 12 cholangiocarcinomas, ten carcinomas of the gallbladder, two advanced ampullary tumors and 12 metastatic tumors. Ten of the patients underwent biliary-enteric bypasses; 18 had stents placed, 11 operatively and nine percutaneously. The remaining eight patients received chemotherapy, radiation therapy or no treatment. Median survival time for patients was 209 days after discharge. Survival was not significantly prolonged for patients with bypass versus those with stents. Achieving and maintaining a bilirubin level of less than or equal to 4 were correlated with survival time (p less than 0.01, p less than 0.001). All ten patients with a bypass versus nine of 18 patients with a stent achieved a bilirubin level of less than or equal to 4 milligrams per deciliter (p less than or equal to 0.01). A multivariate analysis was done using 18 of 27 variables identified by univariate analysis. Albumin was found to be the primary predictor of over-all and hospital-free survival time and was a co-predictor of prolonged maintenance of low bilirubin levels along with biliary-enteric bypass. Placement of a stent was the only predictor of the number of episodes of sepsis and bypass was among the few predictors of length of hospitalization and of over-all morbidity (it was negatively correlated). We concluded that biliary-enteric bypass is the only effective means of palliation in that it improves the quality of life by maintaining low bilirubin levels and minimizing septic complications. Albumin is a strong predictor of survival and maintenance of low bilirubin values and should be a major factor in deciding which patient should undergo a bypass procedure.

Adenoma, Bile Duct↗

Evaluation of children with possible appendicitis using technetium 99m leukocyte scan.

We evaluated the use of technetium 99m albumin colloid white blood cell (TAC-WBC) scan in 33 children with possible appendicitis. Ten children had appendicitis, four of whom had perforated their appendix at the time of surgery. Children with appendicitis differed from children without appendicitis in the incidence of right lower quadrant rebound tenderness (60% vs 17.4%), and white blood cell count (X10(3)/mm3) (14.0 + 1.9 vs 10.7 +/- 1.0). TAC-WBC scans were interpreted as either positive, negative, or indeterminate for appendiceal pathology. Twenty-five children had positive or negative scans for appendiceal pathology. There were 7 true positives, 2 false positives, 16 true negatives, and 0 false negatives. This resulted in a sensitivity of 100%, a specificity of 89%, an accuracy of 92%, a positive predictive value of 78%, and a negative predictive value of 100%. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in eight children (24%), three of whom had appendicitis. The main values of TAC-WBC scan in our study of children with possible appendicitis were that it could be used emergently, it was abnormal in 100% of children with appendicitis, and it had a high negative predictive value (100%). The main limitation of TAC-WBC scan in our study was that it was indeterminate for appendiceal pathology in 24% of children. We recommend that TAC-WBC scan be used in children with possible appendicitis because it may allow outpatient management of up to 48%.

Adolescent↗

Value of measuring hormone receptor levels of regional metastatic carcinoma of the breast.

To assess the value of measuring the estrogen- and progesterone-receptor content of metastatic nodal disease, 38 women with node-positive breast cancer were prospectively evaluated. Receptor content of the primary tumor and a pathologically confirmed positive node were measured simultaneously using a dual-isotope, dextran-coated, charcoal-binding assay. A receptor content of greater than or equal to 10 fmol/mg of cytosol protein was considered positive for both the estrogen-receptor and progesterone-receptor assays. Overall concordance between the primary tumors and the nodal metastases was 82% (31/38 patients) for the estrogen-receptor measurements and 84% (31/37 patients) for the progesterone-receptor measurements. Paired receptor levels were significantly correlated: r = .745 for the estrogen-receptor measurements and r = .805 for the progesterone-receptor measurements. Despite this correlation, 6 (25%) of 24 patients with an estrogen receptor-positive primary tumor had an estrogen receptor-negative nodal metastasis. Four (20%) of 20 patients with a progesterone receptor-positive primary tumor had a progesterone receptor-negative nodal metastasis. Six (24%) of 25 patients with tumors labeled as hormonally sensitive on the basis of the receptor content of the primary tumor had receptor-negative nodal disease. In reflecting the hormonal status of the more aggressive elements of the primary tumor, receptor levels of metastatic nodes may provide more useful information than the levels of the primary tumor as a guideline for further therapy.

Breast Neoplasms↗

Analysis of effect of age on synthesis of specific proteins by hepatocytes.

The effect of age on the synthesis of specific proteins by hepatocytes was studied in Fischer F344 rats using two-dimensional polyacrylamide gel electrophoresis. Almost all proteins synthesized by hepatocytes from young rats were synthesized by hepatocytes isolated from old rats. Of over 500 proteins visually compared by two-dimensional polyacrylamide gel electrophoresis, only 11 proteins were observed to disappear and/or appear consistently with increasing age. The rates of synthesis of 36 randomly chosen proteins were quantified. Interestingly, the synthesis of 35 of the 36 proteins decreased between 5 and 30 months of age. The decrease in protein synthesis varied (15% to 70%) from one protein to another; i.e., a heterogeneity was observed in the age-related decrease in the synthesis of proteins. The age-related decrease in protein synthesis was statistically significant for 53% of the proteins studied. The total decrease in the rate of synthesis of all 36 proteins studied was 40% between 5 and 30 months of age, which is essentially the same as the decrease in total protein synthesis by suspension of hepatocytes isolated from 5- and 30-month-old rats. The results of this study demonstrate that the mechanism underlaying aging is different from development, which is characterized by a major change in the species of proteins synthesized by a cell.

Aging↗

Colorectal cancer in patients younger than 40 years of age.

To assess prognostic factors in patients who develop colorectal cancer before the age of 40 years, a 30-year experience from 1956 through 1985 was reviewed. There were 50 patients ranging in age from 7 to 39 years. Five cases were associated with either ulcerative colitis (2) or familial polyposis (3). The most common presenting symptoms were abdominal pain (66 percent), hematochezia (60 percent), change in bowel habit (41 percent) and weight loss (30 percent). On pathologic staging (N = 44), only 14 of 44 (31 percent) had a Dukes' stage A or B lesion, 20 (45 percent) had Dukes' stage C, and the remaining 10 (23 percent) had distant metastases at the time of surgery. Five-year survival rate was 28 percent with a disease-free survival rate of 18 percent. Median survival was only 28 months. Negative prognostic factors were Dukes' stage C/D (P less than .001), symptom duration of longer than 3 months (P = .01), noncaucasian ancestry (P = .01), and poorly differentiated histology (P = .06). In contrast to older patients with colorectal cancer, only 1 of 30 (3 percent) patients with stage C D disease was disease-free at 5 years. In view of the poor survival rate associated with both delay in diagnosis and the presence of advanced disease, it was concluded that young patients presenting with the symptoms listed above need early, aggressive evaluation for possible colorectal cancer.

Adenocarcinoma↗

Fine-needle aspiration biopsy in the diagnosis of recurrent and metastatic intraabdominal malignancies.

To evaluate the efficacy of directed percutaneous fine-needle aspiration (FNA) biopsy in the diagnosis of recurrent and metastatic intraabdominal malignancies, we reviewed our experience from 1981 to 1988. Seventy-three aspirations were performed in 73 patients. Forty-six patients with a previously treated malignancy had aspiration to diagnose either locally recurrent or metastatic disease. The remaining 27 patients had liver aspiration to rule out metastases from suspected or unknown primary sites. Computed tomography and ultrasonography were equally effective in providing diagnostic material, which was obtained from 68 of 73 aspirates. No serious morbidity occurred. Fifty-seven patients had a metastatic or recurrent malignancy, and 3 had primary hepatocellular carcinoma. Fine-needle aspiration biopsy correctly identified 51 (85 percent) of these 60 cases. There were no false-positive results and five false-negative results. Aspiration results obviated the need for a diagnostic laparotomy in 49 of the 60 patients with malignancy (82 percent). We conclude that directed percutaneous FNA biopsy is a safe and accurate method of diagnosing recurrent and metastatic intraabdominal malignancies.

Abdominal Neoplasms↗

Total gastrectomy in the treatment of advanced gastric cancer.

To assess the role of total gastrectomy in the treatment of advanced gastric cancer, we reviewed the records of 27 patients who underwent the procedure from 1979 to 1988. Operative mortality was 4 percent (1 of 27), and postoperative morbidity occurred in 48 percent of the patients. Twenty-five of 26 patients were tolerating solid food at the time of discharge; 21 were able to maintain oral alimentation until just prior to their death. Median survival following the operation was 15 months (range: 2 to 110 months), with a 62 percent absolute 1-year survival rate and a 38 percent 2-year survival rate. On the basis of these results, we conclude that in patients with advanced gastric carcinoma, total gastrectomy with Roux-Y esophagojejunostomy can be performed with an acceptable morbidity and mortality, provides significant palliation by restoring the patient's ability to eat, and should be performed when technically feasible, even in the presence of gross residual disease.

Adult↗

Hepatic artery versus portal vein and systemic infusion of fluorodeoxyuridine of rabbit VX-2 hepatic implants.

To compare the efficacy of regional and systemic infusions of hepatic tumors, and to correlate this with tumor perfusion, 29 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine (H3-FUDR) and technetium-99m-labeled macroaggregated albumin (Tc 99m-MAA) were infused through the hepatic artery, portal vein, and peripheral vein. Hepatic artery infusion resulted in a significantly improved tumor-to-liver ratio of FUDR uptake (p less than 0.001). The increased tumor uptake correlated with a two-fold increase in tumor arterial blood flow as compared with normal liver demonstrated by the MAA infusion. We conclude that infusional therapy is superior to both portal vein and systemic infusions. Portal vein infusion results in no uptake of drug by the tumor. Hepatic artery scintigraphy with MAA may be useful in selecting appropriate patients for this type of therapy.

Animals↗

Age-related changes in protein phosphorylation by rat hepatocytes.

The qualitative and quantitative changes in the phosphorylation of specific proteins in hepatocyte suspension from 5-, 12- and 22-month-old male Fischer F344 rats were analyzed by two-dimensional polyacrylamide gel electrophoresis. No qualitative changes in phosphorylation of individual proteins were observed with age. In addition, very few quantitative changes (less than 2% of proteins studied) in protein phosphorylation were detected. The phosphorylation of two acidic proteins decreased (50%) with age while the phosphorylation of one basic protein increased (300%) with age. The two acidic proteins and one basic protein that showed quantitative changes with age were found predominately in the microsome and nuclear fractions of hepatocytes, respectively. The effect of dietary restriction on the phosphorylation of proteins in male Fischer F344 rats was also studied. Although, dietary restriction alters the age-related incident of disease and prolongs longevity, it did not have any significant effect on phosphorylation of individual proteins in the liver.

Aging↗

Influence of dietary methionine on the metabolism of selenomethionine in rats.

To determine the influence of methionine on selenomethionine (SeMet) metabolism, weanling male rats were fed for 8 wk a basal diet marginally deficient in sulfur amino acids, containing 2.0 micrograms selenium (Se)/g as DL-SeMet and supplemented with 0, 0.3, 0.6 or 1.2% DL-methionine. Increased dietary methionine caused decreased selenium deposition in all tissues examined but increased glutathione peroxidase (GSHPx, EC 1.11.1.9) activity in testes, liver and lungs. A positive correlation was found between dietary methionine and the calculated percentage of selenium associated with GSHPx. In a second experiment, 75SeMet was injected into weanling male rats which had been fed the basal diet containing 2.0 micrograms selenium as DL-SeMet with or without the addition of 1.0% methionine. The selenoamino acid content of tissues and the distribution of 75Se in erythrocyte proteins were determined. In comparison to the rats fed the basal diet without added methionine, significantly more 75Se-selenocysteine was found in liver and muscle, more 75Se was found in erythrocyte GSHPx and less 75Se was found in erythrocyte hemoglobin of rats fed 1.0% methionine. These data suggest that methionine diverts SeMet from incorporation into general proteins and enhances its conversion to selenocysteine for specific selenium-requiring proteins, such as GSHPx.

Administration, Oral↗

Patterns of response in families of chronically disabled children: an assessment in five metropolitan school districts.

Interviews with parents of 1,726 special education students yielded reports of stress that varied significantly by type of disability and by maternal education level; family involvement in the special education process also varied significantly by level of education. Clinically important differences in family perceptions and coping mechanisms are described and the need for better child care provisions and involvement of low-income parents in the education process is highlighted.

Adaptation, Psychological↗

Efficacy of directed percutaneous fine-needle aspiration cytology in the diagnosis of intra-abdominal masses.

Directed percutaneous fine-needle aspiration (FNA) cytology was performed on 113 patients with intra-abdominal masses. The 47 male and 56 female patients had a median age of 56 years (range, 17 to 83 years). Computed tomography (CT) was used to localize the needle in 90 cases, and ultrasonography was used in the remaining 24 cases. The predominant sites aspirated were the liver (n = 40), pancreas (n = 23), and pelvis (n = 14). Seventy-eight of the 113 patients had a malignant neoplasm. Fine-needle aspiration cytology correctly identified 63 (88%) of the 78 cases. There were no false-positive studies. Computed tomography and UTZ ultrasonography were equally sensitive in detecting malignant neoplasms. In 38 patients with a history of previously treated malignant neoplasm, percutaneous aspiration cytology confirmed the presence of recurrent disease in 24 (75%) of 32 patients. Results of aspiration cytology obviated the need for a diagnostic laparotomy in 51 (65%) of the 78 patients with a malignant neoplasm. There was no serious morbidity or mortality associated with the procedure. We conclude that CT/ultrasonography-directed percutaneous FNA cytology is the procedure of choice in the workup of patients with intra-abdominal masses. The specificity is 100% and sensitivity is 90%. It is particularly useful in patients with extensive disease that would not be palliated by operation.

Abdominal Neoplasms↗

Phagocytic labeling of leukocytes with 99mTc-albumin colloid for nuclear imaging.

A procedure is described for the phagocytic labeling of white blood cells (WBC) with high specific activity 99mTc--albumin colloid (TAC). The preparation contains approximately equal activities of granulocytes and monocytes. Heparinized whole blood (40 cm3) yields a preparation containing a total of 148-222 MBq (4-6 mCi) TAC-WBC including about 20% free TAC. The complete preparation time is 75 min. Imaging is completed 30 min to 4 h post administration of the TAC-WBC. Quality control methods and imaging protocols are described.

Adult↗

Cadaveric renal transplantation: surgical results and expectations in the cyclosporine era.

During a 36-month period 100 patients received 104 cadaveric renal transplants with cyclosporine-based immunosuppression. Of the patients 26 required 31 additional operations. Of the 19 secondary operations performed 1 month after transplantation 18 were emergency in nature, whereas beyond this period the majority of the procedures were elective. Both deaths in this series were related to the operation. Only 1 graft loss was directly attributed to a secondary operation. The patient undergoing cadaveric renal transplantation is at significant risk (25 per cent) of requiring at least 1 additional operation. However, despite this high probability of reoperation, graft loss and patient death after such procedures should be rare.

Adult↗

Appendicitis: evaluation by Tc-99m leukocyte scan.

Diagnosing appendicitis may be difficult. We report the use of a new technetium-99m-albumin colloid white blood cell (TAC-WBC) scan in the evaluation of appendicitis. In a synthesis requiring 75 minutes, autologous neutrophils and macrophages from 40 mL of whole blood were labelled with technetium-99m-albumin colloid and administered to 100 patients with possible appendicitis. The entire process, from labelling the cells to completion of the scan took a maximum of 5 1/4 hours. Two patients had second scans on separate hospitalizations. Twenty-six patients had appendicitis; 12 had perforations, five of whom had an abscess. Eighty-five scans were read as either positive or negative for appendiceal pathology with a sensitivity of 89%, a specificity of 92%, and an accuracy of 92% in diagnosing appendicitis. Seventeen scans were indeterminant; eight of these patients had appendicitis. The value of the TAC-WBC scan in the evaluation of appendicitis lies in its ability to be used emergently, its high negative predictive value for men and women (NPV = 97%), and its high positive predictive value for men (PPV = 93%). At present, the scan does not appear to be reliable in diagnosing appendicitis in women (PPV = 43%). It is most useful in those patients in whom diagnosis is uncertain, and should not be used in patients with clear-cut appendicitis in whom its use will delay definitive surgical care.

Abscess↗

Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta).

Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.

Animal Nutritional Physiological Phenomena↗