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Biomedical subjects

J Foley

Publications and source records attributed to J Foley.

At least 73 records · Page 4Linked to original sources

Leptomeningeal carcinomatosis: a report of 3 cases and review of the literature.

Once thought to be rare, leptomeningeal carcinomatosis from systemic cancer is becoming more common as cancer patients are living longer. Lung, breast and malignant melanoma comprise the majority of solid tumor cases with this condition. The hallmark of the disease and the differential diagnosis are discussed. Only the identification of malignant cells in the cerebrospinal fluid provides as clear-cut diagnosis. Biochemical markers, thus far, cannot substitute for a positive cytology, but may aid in the diagnosis. We report and discuss 3 cases of complete biochemical and radiological assessment and variable degree of aggressiveness of treatment. Better control of the systemic cancer may result in prolongation of life.

Adult↗

Pnemostasis of injured lung in rabbits with gelatin-resorcinol formaldehyde-glutaraldehyde tissue adhesive.

Peripheral bronchopulmonary fistulas, or parenchymal air leaks, may occasionally be resistant to conventional suture or stapling techniques. In such instances, the tissue is poor and the associated morbidity of a persistent leak will be the greatest. We tested a previously described tissue adhesive compounded from gelatin resorcinol and polymerized at the time of application with a glutaraldehyde-formaldehyde mixture. We evaluated the ability of the adhesive to seal incisional air leaks acutely in the lungs of rabbits under conditions of positive intratracheal pressure and persistent ventilation. We also tested the efficacy of the glue at intervals after compounding to assess the shelf life of this nonproprietary formula. We established a technique for application of this adhesive and demonstrated its ability to decrease consistently the magnitude of air leaks, while generally providing complete pneumostasis in the presence of clinically relevant positive pressure ventilation. We conclude that this material can be prepared months in advance of its occasional use as an effective means of dealing with parenchymal air leaks encountered at operation.

Animals↗

Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line.

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.

Cell Differentiation↗

Correlation of hepatocellular proliferation with hepatocarcinogenicity induced by the mutagenic noncarcinogen:carcinogen pair--2,6- and 2,4-diaminotoluene.

2,4-Diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT) are equally genotoxic in the Ames/Salmonella assay and are both readily absorbed, metabolized, and excreted and metabolites of both compounds are mutagenic with metabolic activation. However, there are marked differences in the results of chronic rodent bioassays with these two compounds. 2,4-DAT is a potent hepatocarcinogen whereas 2,6-DAT failed to produce an increased incidence of tumors in any tissue even when administered at a dose higher than that of 2,4-DAT. In an effort to elucidate the source of these apparently discordant results, the present studies were designed to determine the effects of these two chemicals on cell proliferation in the liver when administered at the dose levels comparable to those used in the original bioassays. This study utilized repeated oral dosing, osmotic minipumps to deliver bromodeoxyuridine (BrDU) for 8 days, and immunohistochemistry to quantitate BrDU incorporation into hepatic DNA, CCl4 (0.4 ml/rat, single ip dose) or vehicle control groups were included as positive and negative controls, respectively. The degree of cell proliferation was quantified by the labeling index from at least 1000 hepatocytes. Results from the control studies indicate that approximately 1.1% of the hepatocytes from vehicle-treated animals replicated during the exposure period whereas approximately 50% replicated in the positive controls. The carcinogen 2,4-DAT produced a dose-dependent increase in cell proliferation of approximately 10% and 20% in livers of animals exposed to 12.5 and 25.0 mg/kg/day, respectively, whereas the noncarcinogen 2,6-DAT produced no increase in cell turnover compared to vehicle control following treatment with 25.0 or 50.0 mg/kg/day. These results indicate a positive correlation between increased cell proliferation and hepatocarcinogenesis induced by these two isomers of diaminetoluene.

Animals↗

Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatocarcinogen in rodents. However, liver tumor incidence is increased by TCDD in female Sprague-Dawley rats but not male rats in chronic carcinogen bioassays. Our studies have investigated this finding by evaluating histological and biochemical parameters in a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats (intact and ovariectomized), using diethylnitrosamine (DEN) as the initiating agent and TCDD as the promoting agent. Increases in gamma-glutamyl transpeptidase-positive foci were greater in intact female rats than in ovariectomized (OVX) animals. For example, in intact rats receiving both DEN and TCDD, the percentage of liver occupied by gamma-glutamyl transpeptidase-positive foci was 0.37, compared to 0.08 in OVX rats. Values for intact or OVX rats receiving either DEN or TCDD only were 0.04 or less. Similar results were obtained when using placental glutathione S-transferase to detect hepatic preneoplastic lesions. Cell proliferation data, obtained using bromodeoxyuridine in osmotic minipumps, were consistent with preneoplastic foci data in that the hepatocyte labeling index was increased in DEN/TCDD intact rats but not in DEN/TCDD OVX rats. Analysis of data from individual animals revealed a strong correlation (P less than 0.01) between cell proliferation and placental glutathione S-transferase-positive foci/cm3 in liver. These findings did not reflect effects of ovariectomy on TCDD tissue distribution, since livers of OVX rats contained more TCDD than livers of intact rats, although both groups of rats received a dose of 1.4 micrograms TCDD/kg once every 2 weeks for 30 weeks. Hepatic cytochrome P-450d (IA2) was induced approximately 6-8-fold in all TCDD-treated groups, and the magnitude of induction was not influenced by ovariectomy. This cytochrome efficiently catalyzes metabolism of 17 beta-estradiol to catechol estrogens. Our data suggest that ovarian hormones (probably estrogen) play a significant role in the hepatocarcinogenic actions of TCDD.

Animals↗

Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease.

BACKGROUND: The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated. METHODS: Seventeen children and young adults (mean [+/- SD] age, 14.1 +/- 3.7 years) undergoing regular peritoneal dialysis were randomly assigned to treatment with either aluminum hydroxide (n = 7; maximal dose, 30 mg per kilogram of body weight per day) or calcium carbonate (n = 10; dose range, 2.5 to 12 g per day, according to serum phosphorus levels). Aluminum retention was assessed by serial measurements of plasma aluminum, deferoxamine-infusion tests, and measurements of bone aluminum content during a mean (+/- SD) follow-up of 13 +/- 2 months. The evolution of bone disease was also evaluated. RESULTS: Plasma aluminum levels and the increment in plasma aluminum after infusion of deferoxamine increased from base-line values in the patients treated with aluminum hydroxide, and aluminum-related bone disease developed in one patient. Serum phosphorus levels remained higher and serum calcium levels lower in the patients receiving aluminum hydroxide than in those receiving calcium carbonate. The skeletal lesions of secondary hyperparathyroidism improved in 7 of 10 patients receiving calcium carbonate but persisted or progressed in 6 of 7 patients given aluminum hydroxide (P less than 0.025). CONCLUSIONS: Aluminum hydroxide is less effective than calcium carbonate as a phosphate-binding agent for the control of hyperphosphatemia and is associated with aluminum retention in children and young adults with chronic renal failure who are receiving dialysis therapy.

Adolescent↗

Influences of marital status and parental status on the professional choices of physicians about to enter practice.

The trend toward increasing numbers of working women may alter the ways both men and women physicians structure their professional lives. The 1987 graduates of residency and fellowship programs at the University of Minnesota Medical School--Minneapolis were surveyed in June 1987 about professional plans and factors that led to their decisions. The women expected that their spouses would contribute half of their family's income, whereas the men expected that they would be largely responsible for their family's income. The married women with children planned on working fewer hours than did other physicians. Family structure may play an important role in preventing the convergence of men and women physicians' personal incomes or working hours.

Career Choice↗

The in vivo manipulation of alcohol-related beliefs in male social drinkers in a naturalistic setting.

Earlier research shows that alcohol expectancies are related to alcohol consumption. However, how the alcohol expectancies are related to drinking in a public bar is still unknown. This paper examines this relationship in 10 moderate-heavy male social drinkers attending alternatively to both alcohol dependent and non-dependent cognitive sets of alcohol use. When discussing the alcohol dependent expectancies, these drinkers consumed significantly less alcohol compared with their consumption when discussing non-alcohol dependent expectancies. This group effect was also corroborated by a within-subject analysis of the data. The implications of the relationship between beliefs and drinking behaviour in terms of a cognitive behaviour model of alcohol use are briefly discussed.

Adult↗

Targeting of peritoneum by the small numbers of isogeneic and allogeneic ascites carcinoma cells that infiltrate or attach to peritoneum during ascites growth.

In the course of development of an in vivo invasion model, sublines of a series of allogenic and isogeneic carcinoma cell lines have been selected that show enhanced invasion of the peritoneum. It was found that, during the proliferation of tumor cell lines in ascitic form in the abdominal cavity, small numbers of cells infiltrated or firmly adhered to the peritoneum in at least 8/12 of the tumor-host combinations tried. After thorough washing of the peritoneum it was disaggregated by an enzyme mixture, and the resulting mixture of normal and tumor cells was inoculated intraperitoneally. Peritoneal isolations were made serially for 3 to 12 times. In 6 of 8 cases where the isolation produced a stable ascites, the cells showed enhanced peritoneal invasion compared with the parent cell line. The invasion of some of the cell lines was tested in another invasion model consisting of cultured mouse buccal mucosa (9/10 cell lines invaded the explant). In 3/3 cell lines showing enhanced peritoneum invasion in vivo, there was no enhanced invasion of the buccal mucosa. The enhanced peritoneum invasion appears to be tissue specific rather than a general increase in invasion potential. Pairs of high- and low-invasive cell lines were obtained that should be useful for screening for invasion modulating agents using the mouse ascites/peritoneum in vivo model. It is suggested that the method might be generalized to produce various tumor cell lines that target for the normal tissues that are adjacent to proliferating solid or circulating tumors.

9,10-Dimethyl-1,2-benzanthracene↗

Education costs in two public teaching hospitals.

The authors examined the impact of costs of education on the overall expenses of two major teaching hospitals during a period of rapid growth and change in the Minneapolis and St. Paul, Minnesota, health care environment. By using a retrospective faculty-time study and the two hospitals' estimated costs for education, education costs of each hospital were compared--within and across facilities--with annual hospital operating expenses, with inflation, and by educational program. Unit costs were estimated for undergraduate and graduate medical students. Over the study period, allocated education costs averaged 13-14% of the hospitals' operating budgets. The combined mean allocated cost per medical student and resident was approximately +73,000 in 1983-84. During this period, allocated education costs were in line with medical inflationary trends and did not drive hospital expense increases. These findings suggest that policymakers wishing to restrain the rise in health care costs should look beyond cutting the costs of education programs and find other solutions.

Academic Medical Centers↗

Prognosis in stroke.

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Cerebrovascular Disorders↗

Hyperlipidemia in pediatric patients undergoing peritoneal dialysis.

We evaluated serial measurements of serum lipid levels in 68 patients aged 12.6 +/- 4.7 years undergoing treatment with continuous ambulatory peritoneal dialysis/continuous cycling peritoneal dialysis (CAPD/CCPD). Fasting mean levels of triglycerides (TG) and cholesterol (C) were elevated above the 95th percentile of published normal values by 102% and 19%, respectively, at the start of dialysis. Except for a short-term decrease in TG levels at 6 and 9 months, no significant change in mean lipid levels was observed during a follow-up period of 2 years. At initiation of dialysis, elevated TG and C levels were present in 90% and 69% of the patients, respectively. The prevalence of hyperlipidemia (HL) varied between 63% and 88% (TG) and 61% and 93% (C), respectively, during the follow-up period. TG and C levels were not correlated with caloric intake (evaluated in 17 patients), serum albumin levels, treatment modality (CAPD or CCPD), a history of the nephrotic syndrome, or previous treatment with hemodialysis or transplantation. However, a significant inverse correlation was observed between age and serum lipids at the initiation of dialysis treatment and after 1 year (TG: r = -0.40; C: r = -0.44). Our data indicate a high prevalence of HL but no significant change of serum lipid levels during 2 years of treatment with CAPD/CCPD.

Adolescent↗

Acquired cystic kidney disease in children undergoing long-term dialysis.

Acquired cystic kidney disease (ACKD) occurs in adult patients undergoing long-term dialysis. Early detection is important because clinically significant hematuria and malignancies are associated with ACKD. We evaluated by magnetic resonance imaging (MRI) and ultrasonography (US) the incidence of ACKD in 15 patients aged 7.3-21.6 years (mean 15.9 years) with non-cystic primary renal disease. Nine patients had been treated with peritoneal dialysis only, and 6 with both hemodialysis and peritoneal dialysis for 24-73 months (mean 37 months). Three patients (20%) had no cysts. In 5 patients (33%) with bilateral multiple cysts, the diagnosis of ACKD was made by MRI and US. In another 5 patients, solitary cysts were localized to one kidney by MRI, and in 2 patients solitary cysts were seen in both kidneys. This study documents that ACKD is not limited to older patients with end-stage renal disease. Early detection of these cysts can be accomplished by MRI and is warranted since 1 patient developed neoplastic tubular changes which can precede tumor formation.

Adolescent↗

Botulinum neurotoxin type A: cleavage of the heavy chain into two halves and their partial sequences.

The 145-kDa type A botulinum neurotoxin (NT) is produced by the bacteria Clostridium botulinum (strain, Hall). The heavy (H) and light (L) chains (97- and 53-kDa, respectively) of this protein are linked by at least one disulfide bond. The N- and C-terminal halves of the H chain appear to have different functions in the mechanism of action of the NT [1987) FEBS Lett. 226, 115-120). Well-characterized and highly purified preparations of the two halves of the H chain are needed for such studies. Two different approaches were taken to cut the H chain with trypsin and isolate the fragments. In one method the cleavage products were: (i) 94-kDa fragment made of the L chain linked to the N-terminal half of the H chain (49 kDa) by a disulfide bond(s), and (ii) the C-terminal 44-kDa fragment. The N-terminal half of H chain was separated from the L chain by reducing the disulfide bond(s) linking them and then purified by ion-exchange chromatography. The 1-27 residues of 49-kDa N-terminal half of the H chain were Ala-Leu-Asn-Asp-Leu-Cys-Ile-Lys-Val-Asn-Asn-Trp-Asp-Leu-Phe-Phe-Ser-Pro- Ser-Glu - Asp-Asn-Phe-Thr-Asn-Asp-Leu-. The sequence of the other half of the H chain (44 kDa) was X-Ile-Ile-Asn-Leu-X-Ile-Leu-Asn-Leu-Arg-Tyr-Glu-X-Asn-His-Leu-Ile-Asp-Le u-Lys- X-Tyr-Ala-Ser-. In the second method, the H chain was first separated from the L chain, purified, and then cleaved. One product of cleavage, the 44-kDa fragment, was partially sequenced; the first 25 residues were identical to the sequence of the 44-kDa fragment generated by the first method. The present work also demonstrated that (i) The cysteine residue(s) located on the N-terminal half of the H chain form the -S-S- link(s) with the L chain. (ii) The other half of the H chain (44-kDa fragment, apparently the C-terminal half) is not linked via -S-S- to the L-chain or to the N-terminal half (49-kDa fragment) of the H chain.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD.

The histologic features of renal osteodystrophy and the prevalence of bone aluminum deposition in children receiving regular dialysis have not been described. Forty-four pediatric patients undergoing continuous ambulatory (CAPD) or cycling (CCPD) peritoneal dialysis had bone biopsies and deferoxamine (DFO) infusion tests; all were receiving oral calcitriol. Osteitis fibrosa (OF) was found in 39%, mild lesions (M) in 25%, normal histology (NH) in 16%, aplastic lesions (AP) in 11%, and osteomalacia (OM) in 9%. Bone surface aluminum (SA) was present by histochemical staining in 10 out of 20 given aluminum-containing phosphate-binding agents and in 0 of 24 treated with calcium carbonate; chi 2 = 15.5, P less than 0.0001. Serum biochemistries and DFO infusion tests failed to predict bone histology, but plasma aluminum levels were markedly elevated and bone aluminum content was highest in patients with OM. Bone formation rate (BFR) correlated with serum parathyroid hormone (PTH), r = 0.55, P less than 0.001; BFR was inversely related to bone aluminum content (r = -0.42, P less than 0.01), even in patients with OF (r = -0.66, P less than 0.05). All patients with SA greater than 30% had normal or reduced BFR when compared to those with SA less than 30%; chi 2 = 12.2, P less than 0.005. Based on SA greater than 30%, six patients were classified as aluminum-related bone disease: three OM, one AP, and two NH. Two-thirds of pediatric patients undergoing CAPD/CCPD have persistent hyperparathyroidism despite treatment with calcitriol, but aluminum can adversely affect BFR when SA exceeds 30% regardless of histologic lesion or serum PTH level.

Aluminum↗

Mechanisms of mitochondrial photosensitization by the cationic dye, N,N-bis(2-ethyl-1,3-dioxylene)kryptocyanine (EDKC): preferential inactivation of complex I in the electron transport chain.

We investigated mechanisms of mitochondrial phototoxicity caused by the cationic cyanine dye N,N'-bis(2-ethyl-1,3-dioxylene)kryptocyanine (EDKC), examining the role of the mitochondrial membrane potential on the dye uptake by carcinoma cells in vitro, and both the dark and photosensitizing effects of the dye on the function of isolated mouse liver mitochondria. When human bladder carcinoma cells (EJ) were pretreated with 2,4-dinitrophenol or nigericin, cellular uptake of EDKC decreased or increased, respectively, consistent with dye uptake that is dependent on membrane potentials. In isolated liver mitochondria, during NADH linked substrate oxidation (using glutamate plus malate or beta-hydroxybutyrate as substrates), low concentrations of the dye (0.25-0.5 microM) sensitized mitochondria to illumination with long wavelength light and inhibited both basal and ADP-stimulated respiration. Similar effects were observed during succinate oxidation, but only at higher concentrations of EDKC (greater than 5 microM) and at 10-fold greater light doses. NADH coenzyme Q reductase (Complex I) activity was inhibited by dye with or without light to an extent comparable to the inhibition of glutamate plus malate oxidation. Activity of cytochrome c oxidase, the terminal enzyme in the electron transport chain, was photosensitized with high dye doses (greater than 5 microM) and light, but the extent of inhibition was much less than the inhibition of respiration with succinate as substrate. ATP synthetase (F0F1 ATPase) activity was minimally affected by 4.0 microM EDKC with or without 24 J/cm2 light. We conclude that at low concentrations of dye, respiratory Complex I is a primary target for EDKC dark and light-induced toxicities. If Complex I is bypassed by using succinate as a respiratory substrate, the mitochondria can tolerate much higher dye concentrations and light doses.

2,4-Dinitrophenol↗