Will community physicians participate in rigorous studies of cancer control? The methodology and recruitment of a randomized trial of physician practices.
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Adult↗
Biomedical subjects
J Barrett
Publications and source records attributed to J Barrett.
Subxiphoid pericardiotomy versus echocardiography: a prospective evaluation of the diagnosis of occult penetrating cardiac injury.
Diagnostic subxiphoid pericardiotomy (SP) is presently advocated for the diagnosis of occult cardiac injuries in patients with stable vital signs with juxta-cardiac-penetrating chest wounds. This approach, however, results in a reported 80% negative pericardial exploration rate. To investigate the reliability of bedside two-dimension echocardiography (2-D echo) in predicting cardiac injury as compared to SP, a prospective study was undertaken of patients with stable vital signs who were admitted with penetrating chest wounds that were located within the space bounded by the manubrium, nipples, and subcostal line. Initial evaluation of the patients with bedside 2-D echo was found to have a 96% accuracy, 97% specificity, and 90% sensitivity in predicting cardiac injury. The only false-negative findings were in a patient who consented to SP 18 hours after bedside 2-D echo was performed. The reliability of bedside 2-D echo compared to SP was not significantly different according to the kappa measure of reliability. These data suggest that bedside 2-D echo is an expeditious and reliable method to diagnose occult cardiac injuries during the initial assessment of a patient with stable vital signs who had penetrating chest trauma. This approach may allow for the selective use of SP on patients with positive bedside 2-D echo and could eliminate unnecessary surgical procedures.
Echocardiography↗
Drugs and the bone marrow.
Some drugs have a predictable suppressive effect upon the bone marrow and are used in the treatment of malignant disease. Others are unpredictable and may cause unanticipated side effects to bone marrow during the treatment of non-malignant pathologies. In this article, bone marrow maturation is discussed and both the defined and potential effects of drugs upon the bone marrow are considered.
Agranulocytosis↗
1,25-Dihydroxyvitamin D3 induces normal mononuclear blood cells to differentiate in the direction of monocyte-macrophages.
Normal blood mononuclear cells incubated in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in suspension culture showed increased differentiation to adherent macrophages. The effect was specific to 1,25-(OH)2D3 as the closely related metabolite 25-hydroxyvitamin D3 did not increase macrophage numbers. Giant multinuclear cells were observed in increased numbers in 1,25-(OH)2D3-treated cultures. However this effect was not specific to 1,25-(OH)2D3 but due to cell crowding as these cells were also plentiful when cultures without 1,25-(OH)2D3 were incubated at high cell densities. Increased numbers of macrophages were seen after six days of incubation; this effect of 1,25-(OH)2D3 occurred also if the mononuclear cells were depleted of T-cells or exposed to X-irradiation at doses up to 25Gy. Addition of 1,25-(OH)2D3 to cultures in semi-solid media did not, however, increase the numbers of monocyte-macrophage colonies. These results suggest that the target cell for 1,25-(OH)2D3 is of the monocyte-macrophage lineage and is at a relatively late stage of maturation.
Calcitriol↗
A simple matrix method for determining flux control coefficients in complex pathways.
Flux control coefficients express in quantitative terms the extent to which the steady state flux through a metabolic pathway is controlled by a particular parameter. Enzyme flux control coefficients can be calculated using matrix algebra methods which express the control coefficients in terms of parameters which can be determined experimentally (enzyme elasticities, flux ratios, metabolite ratios). This paper describes an algorithm based on a 'constraint' matrix which enables expressions for enzyme control coefficients to be written for pathways of any complexity.
Algorithms↗
Glutathione transferases in the tapeworm Moniezia expansa.
Four forms of GSH transferase were resolved from Moniezia expansa cytosol by GSH-Sepharose affinity chromatography and chromatofocusing in the range pH 6-4, and the presence of isoenzymes was further suggested by analytical isoelectric focusing. The four GSH transferase forms in the cestode showed no clear biochemical relationship to any one mammalian GSH transferase family. The N-terminal of the major GSH transferase form showed sequence homology with the Mu and Alpha family GSH transferases. The major GSH transferase appeared to bind a number of commercially available anthelmintics but did not appear to conjugate the compounds with GSH. The major GSH transferase efficiently conjugated members of the trans-alk-2-enal and trans,trans-alka-2,4-dienal series, established secondary products of lipid peroxidation.
Amino Acid Sequence↗
The possible absence of cytochrome P-450 linked xenobiotic metabolism in helminths.
The distribution of cytochrome P-450, b5 and associated oxidations, aniline hydroxylase, 7-ethoxycoumarin O-deethylase and 4-nitroanisole O-demethylase were studied in the parasitic nematode Heligmosomoides polygyrus, its mammalian host, Mus musculus and the free-living nematode Panagrellus redivivus. Cytochrome P-450, its associated oxidations and cytochrome b5 could not be detected in whole homogenates or subcellular fractions (mitochondrial, microsomal and soluble fractions) of either nematode under a variety of assay conditions which included attempted induction with sodium phenobarbital. P. redivivus was able to reduce 1,2-dimethyl-4-(4-carboxyphenylazo)-5-hydroxybenzene and azobenzene, which is predominantly microsomal. The implications of these results in terms of chemotherapy are discussed.
7-Alkoxycoumarin O-Dealkylase↗
Colorectal trauma.
Surgical treatment of colon and rectal trauma continues to challenge physicians. Injuries to a colon or rectum filled with feces results in subsequent peritoneal contamination which will lead to severe septic complications unless dealt with promptly and correctly. The authors have reviewed the records of 242 patients with colon and rectal trauma operated on at the Cook County Trauma Unit from July 1, 1973 to December 31, 1983, to evaluate treatment results. The mechanism of trauma was penetrating in 233 of 242 patients. Most, if not all, colonic lesions were treated with either exteriorization, resection and no anastomosis, or closure and proximal colostomy. Mortality related to colonic injury was 2.5 percent. Morbidity related to colonic injury included wound infection, 6.3 percent; abscess, 2.5 percent; other, 3.3 percent. Despite the severity of the trauma, adherence to conservative principles of "no anastomosis" in the overwhelming majority of cases has resulted in low morbidity and mortality.
Adolescent↗
The detoxification of xenobiotic compounds by Onchocerca gutturosa (Nematoda: Filarioidea).
In common with other helminths O. gutturosa appears to lack cytochrome P450 linked phase 1 enzymes and so its ability to metabolize aromatic nuclei may be severely restricted. The parasite could reduce azo- but not nitro-compounds and low levels of epoxide hydrolase activity were also detected. Glutathione S-transferase was the only phase 2 enzyme which could be demonstrated in O. gutturosa. High levels of glyoxalase I and in particular glyoxalase II were found in the parasite, suggesting an important role for these enzymes in detoxification.
Animals↗
Purification of cytosolic glutathione transferases from Schistocephalus solidus (plerocercoid): interaction with anthelmintics and products of lipid peroxidation.
Glutathione (GSH) transferase isoenzymes have been partially resolved from the cytosol of Schistocephalus solidus (plerocercoid) by GSH affinity chromatography and chromatofocusing at pH 7-5. The presence of isomeric forms was also suggested by analytical isoelectric focusing and high-performance liquid chromatography (HPLC). Gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that GSH transferase forms were dimers with a subunit size of approximately 24 kDa. The major GSH transferase form in S. solidus (plerocercoid) showed greater biochemical relationship to the Mu family of mammalian GSH transferase compared to the mammalian Alpha or Pi families. The major subunit purified by GSH affinity chromatography and reversed-phase HPLC also showed high N-terminal homology with the Mu family. A minor GSH transferase form appeared more biochemically related to the Alpha family with respect to substrate specificity and inhibitor sensitivity. The major GSH transferase was inhibited by haematin-related compounds, bile acids and a number of anthelmintics including members of the benzimidazole and phenol-based class of compounds. The major GSH transferase had conjugating activity with members of the trans, trans-2,4-alkadienal and trans-2-alkenal series, secondary products of lipid peroxidation.
Amino Acid Sequence↗
Xenobiotic metabolism in helminths.
During its life cycle a parasite, like mammals and other organisms, comes into contact with a variety of toxic molecules. In mammals the main line of defence against such compounds is a group of oxidative enzymes that occur predominantly in the liver. Many of these oxidations are dependent on the haemoprotein cytochrome P-450 which serves as a terminal oxidase accepting electrons from NADPH and cytochrome [Formula: see text] . This review by Wendy Precious and John Barrett illustrates that in contrast to mammals, xenobiotic metabolism in both parasitic and free-living platyhelminths and nematodes is predominantly reductive and hydrolytic as the cytochrome P-450 system is absent. This is surprising since it is present in many groups including bacteria, fungi and protozoa, which suggests an ancient origin. The absence of the cytochrome P-450 system not only severely limits the ability of helminths to detoxify compounds but also limits their ability to activate prodrugs.
Journal Article↗
Renin regulation in type II diabetes mellitus: influence of dietary sodium.
Numerous abnormalities in the renin-angiotensin system have been described in diabetes mellitus. Plasma renin activity (PRA) has been noted to be low, normal, and high in diabetic patients; these variable results may be explained by differences in patient selection and standardization of study conditions. We evaluated PRA and inactive renin responses in Type II normotensive (n = 7) and hypertensive (n = 12) diabetic patients specifically selected for no or minimal evidence (background retinopathy) for microvascular complications. Patients were studied in a metabolic ward after 7 days on a constant low sodium (20 meq/day) and 7 days on a high sodium (250 meq/day) diet. Nondiabetic control subjects (n = 7) were evaluated under similar conditions. On low sodium intake, mean PRA levels were significantly reduced in the hypertensive diabetic group, but were not different between the control and normotensive diabetic groups. Hypertensive diabetic patients on high sodium intake also had greater reductions in PRA responses compared with the other study groups. In general, diabetic subjects on high sodium intake excreted less sodium and had more cumulative sodium retention than control subjects. Levels of inactive renin were not significantly different between the normotensive and hypertensive diabetic patients and were comparable with the levels in control subjects. Inactive renin levels changed in a similar direction and magnitude as PRA in response to sodium intake and posture in the three study groups. Infusion of angiotensin II led to comparable reductions in PRA in both diabetic groups and in the control group, suggesting an intact short feedback loop control.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Nicotine gum and smoking cessation.
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Adult↗
Experimental cyclosporin hypertension: characterization of the rat model.
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Animals↗
Cerebral blood flow following hypertonic saline resuscitation in an experimental model of hemorrhagic shock and head injury.
Hypertonic (3.0%) saline (HS) resuscitation from hemorrhagic shock is associated with less cerebral edema and lower intracranial pressure (ICP) compared to normal saline (NS) and 10% Dextran 40 (D-40). The effect of HS resuscitation on cerebral blood flow (CBF) is unknown. Beagle dogs with a head injury underwent shock and resuscitation, receiving either NS (N = 6), HS (N = 6), or D-40 (N = 6). CBF (via a microsphere technique) and ICP were measured at baseline (BL) and at end shock (ES) after infusion of shed blood and test fluid (ER) and 2 hours after resuscitation (LR). CBF was determined globally (GCBF), and for the right (RCBF) and left (LCBF) cerebral hemispheres. ICP values (+/- SEM) at BL and ES were 10.8 +/- 1.31 mmHg and 8.0 +/- 1.67 mmHg, respectively, for all groups. GCBF, RCBF and LCBF at BL were 29.4 +/- 5.04, 26.7 +/- 4.93 and 26.6 +/- 4.50 ml 100 g-1 min-1, respectively. ES values for CBF were not significantly different from BL. Global and hemispheric CBF values were not different between groups at times measured. ICP was significantly lower in animals receiving HS. Therefore, lower ICP following HS resuscitation is not associated with alteration in CBF.
Animals↗
HCFA proposals would hold physician payment increases to 10% in fiscal 1988.
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Centers for Medicare and Medicaid Services, U.S.↗
The intraperitoneal delivery of radiolabeled monoclonal antibodies: studies on the regional delivery advantage.
The i.p. delivery of murine monoclonal antibody was compared with i.v. delivery in normal mice and rats, in normal nude mice and in those with i.p. human ovarian carcinoma xenografts. In normal rats, all classes of antibodies and antibody fragments evaluated were cleared from the peritoneal cavity at comparable rates. The regional delivery (Rd1) advantage to the peritoneal cavity following i.p. delivery was thus most dependent on the rate of clearance of the antibody or fragment from the blood stream. Determining the exact i.p. delivery advantage was problematic due to the difficulty in reliably obtaining peritoneal fluid later than 9-10 h after i.p. injection in normal animals. During the first 9 h following i.p. injection, the Rd(0-9/0-9) was, for a murine IgG2ak Fab greater than F(ab')2 greater than IgG (at 13.6 greater than 10 greater than 7.9). Two murine IgMs evaluated differed in Rd(0-9) at 27.1 and 9.2 respectively. When blood levels were extrapolated to infinity, these Rd (0-9/affinity) values were considerably lower with the Fab having the highest Rd at 4.67. The i.p. Rd advantage was almost solely due to the i.p. antibody levels seen in the first 24 h after injection, as after that time, blood levels become comparable to those seen following i.v. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. injection. Normal tissues obtained at sacrifice 5-7 days after i.p. or i.v. injection in rats showed comparable levels of radioantibody activity, whether the injection was i.p. or i.v. (except for higher diaphragmatic levels following i.p. delivery). In nude mice with i.p. human-derived ovarian tumors, intact IgG clearance from the peritoneal cavity to the blood was considerably slower than in normal animals, and early i.p. tumor uptake of specific antibody was significantly higher than that following i.v. antibody delivery. With higher early tumor uptake and lower systemic exposure, early tumor/nontumor ratios were significantly greater than those for i.v. delivery, though not beyond 48 h after i.p. injection. This study demonstrates the pharmacokinetic rationale for i.p. monoclonal antibody delivery, especially for agents cleared rapidly from the blood, such as antibody fragments. In addition, definite i.p. delivery benefit for antibody specific to i.p. tumors in the i.p. ovarian cancer system was shown soon after injection. These data regarding i.p. antibody delivery should be useful in rationally planning diagnostic and therapeutic studies involving the i.p. delivery of unmodified and immunoconjugated monoclonal antibodies.
Animals↗
Selective effect of mannitol-induced hyperosmolality on brain interstitial fluid and water content in white matter.
We studied the effect of mannitol-induced hyperosmolality on brain interstitial fluid (ISF) by autoradiography. Adult cats underwent intracerebral infusion of the extracellular marker, 14C-sucrose. Nine animals were given 2g/kg of mannitol intravenously, and another nine animals without mannitol were controls. Plasma and cerebrospinal fluid (CSF) osmolalities were measured. After 2 hr the brains were removed for determination of water and electrolyte content and for preparation of the autoradiograms. Diffusion coefficients were calculated for intracerebral transport with equations for radial diffusion. We found that mannitol increased the plasma osmolality but did not affect that of the CSF. Water and potassium contents were significantly lower in the white matter of mannitol-treated animals than in controls. Diffusion was reduced in the direction of gray matter into the white matter. We conclude that lower doses of mannitol control CSF pressure by selectively removing water from white matter, reducing the CSF volume, and affecting molecular transport at the gray/white interface.
Animals↗