Turning transfer trauma to triumph.
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Biomedical subjects
Publications and source records attributed to P Murphy.
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In a randomized, double-blind study, cystic fibrosis patients 11-30 years of age with an acute exacerbation of their pulmonary disease were treated with either ticarcillin-tobramycin, azlocillin-tobramycin, or azlocillin-placebo for 10 days. There was significant improvement in Shwachman scores and pulmonary function tests. Concentrations of sputum bacteria were significantly reduced, but after therapy patients had a mean of 10(7) bacteria/ml of sputum. Pseudomonas was transiently eliminated in only one patient. The three regimens had similar impacts on pulmonary function and sputum bacterial concentration. Antibiotic resistance was noted more frequently in the azlocillin-placebo group, but this trend was not statistically significant. Improvement in pulmonary function did not correlate with bacteriological response. Four weeks after discharge, 62% of the improvement in forced expiratory volume in one second and 75% of the improvement in vital capacity remained, but concentrations of sputum bacteria had returned to pretreatment levels, and antibiotic-resistant bacteria persisted.
The in vitro activity of rifampin alone and in combination with oxacillin was determined for 75 Staphylococcus aureus strains (64 susceptible and 11 resistant to oxacillin). Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined by broth microdilution; antibiotic combinations were evaluated by microdilution checkerboard and time-kill studies. The 90% MIC of rifampin was less than or equal to 0.015 micrograms/ml after both 24 and 48 h of incubation. The 90% MBC of rifampin was less than or equal to 2.0 micrograms/ml on subculture at 24 h of incubation and less than or equal to 0.5 micrograms/ml on subculture at 48 h. MIC checkerboards with oxacillin-susceptible strains revealed an additive or indifferent effect in 35 strains (55%) and antagonism in 29 strains (45%). MBC checkerboards performed by subculture at 24 h demonstrated antagonism for all but one of the oxacillin-susceptible strains, with sub-MBCs of rifampin impairing the bactericidal activity of oxacillin. MBC checkerboards performed by 48-h subculture revealed antagonism with 37 strains (58%); in 26 additional strains (40%), a synergistic, additive, or indifferent effect was observed at low antibiotic concentrations, but antagonism was seen at higher concentrations. Time-kill studies tended to show indifference rather than antagonism with oxacillin plus rifampin. In checkerboards performed with oxacillin-resistant strains, the addition of rifampin did not improve oxacillin inhibitory or bactericidal activity to a clinically significant extent; however, the addition of oxacillin improved the bactericidal activity of rifampin at easily achievable serum concentrations.
Keratinocytes, the predominant cell within the epidermis, perform some macrophage-like functions, such as endocytosis and phagocytosis. We therefore investigated whether keratinocytes may also exert some nonspecific immunoregulatory functions through the secretion of mediators. Tissue cultures of freshly isolated murine and human keratinocytes as well as keratinocyte cell lines secrete a cytokine, epidermal cell-derived thymocyte-activating factor (ETAF), which augments in vitro lymphoproliferative responses. Keratinocyte cell line cells produce increased levels of ETAF activity after exposure to a variety of cell-damaging agents such as silica, endotoxin, phorbol myristate acetate, hydroxyurea, and mechanical disruption. Biochemical studies showed that murine and human ETAF, like interleukin 1 (IL 1), had a molecular weight between 12,000 and 20,000, interacted with hydrophobic phenyl-Sepharose, and was eluted from anion but not cation exchangers. Like IL 1, murine ETAF had a single isoelectric point whereas human ETAF eluted as three peaks of activity (pI 7.2, 5.8, and 5.0). Partially purified ETAF of either species also had the same biological properties of IL 1. That is, ETAF enhanced IL 2 production by T cells in culture, was chemotactic for polymorphonuclear leukocytes, and was directly mitogenic for fibroblasts. When injected into C3H/HeJ mice ETAF induced hepatocyte production of serum amyloid A, an acute phase protein. Furthermore, ETAF, like IL 1, may act as an endogenous pyrogen and induce fever when injected into rabbits. These findings indicate that production of IL 1-like molecules is not confined to cells of the immune system and that ETAF production by keratinocytes may have important implications in would healing, as well in the pathogenesis of inflammatory and neoplastic diseases.
D-Xylose kinetics were studied in 12 normal subjects and in nine patients with chronic renal failure requiring dialysis (five hemodialysis and four peritoneal dialysis). None of the study subjects had demonstrable gastrointestinal disease. Doses of D-xylose were given intravenously (10 gm) and orally (25 gm) on different nondialysis days in order to determine the distribution and elimination kinetics and the absolute bioavailability of this compound. Our findings were as follows. (1) The nonrenal clearance of D-xylose is markedly reduced in chronic renal failure patients (43.3 vs. 90.9 ml/min, p less than 0.002). (2) D-Xylose is less completely absorbed in patients with chronic renal failure than in normal subjects (48.6% vs. 69.4%, p less than 0.01). (3) The absorption rate of D-xylose is slower in these patients than in normal subjects (0.555 hr-1 vs. 1.03 hr-1, p less than 0.05). (4) The absorption rate is positively correlated with the extent of D-xylose absorption (r = 0.49, p = 0.03). (5) Although peak D-xylose concentrations measured 1 hr after oral administration are well correlated with the extent of D-xylose absorption in normal subjects and in functionally anephric patients (r = 0.59, p less than 0.01), formal kinetic study is required to determine D-xylose bioavailability precisely because of the large variability in peak serum D-xylose concentrations and in the time required to reach these peak concentrations.
Of 191 case reports submitted to the National Soft Tissue Sarcoma Registry, 131 qualified for inclusion. Fifty-two percent were males; 80% were whites. Twenty-one different histologies were assigned, with leiomyosarcoma most frequently represented. Localized disease was reported for 29% of patients. Surgery in combination with radiotherapy and/or chemotherapy was reported as the treatment for 45% of patients, and surgery only was reported for 31%. These data reflect increasing used of adjuvant therapy in the treatment of soft tissue sarcoma.
There are frequent reports of impairment of psychomotor performance on the morning after taking hypnotics. Possible ways of avoiding these problems include a reduction of the dose or using a hypnotic with a short half-life. This study used nitrazepam 2.5 mg and triazolam 0.125 mg in a group of hospitalized elderly patients. Both drugs were effective hypnotic agents but they are different in their residual effects. Patients reported difficulty in waking after nitrazepam but not after triazolam. These difficulties were confirmed by nurse observation. Nitrazepam significantly impairs (after repeated doses) psychomotor performance after five days therapy and this effect was not seen after triazolam. If a benzodiazepine hypnotic is used in the elderly, a drug with a short elimination half-life is an advantage.
Intracellular deoxynucleoside triphosphate pools of normal bone marrow, thymocytes and cells from patients with ALL and AML were measured after 2 h incubation with deoxycoformycin (dCF) 10(-5) M and deoxyadenosine (AdR) 10(-4) M in vitro and after another 30 min incubation in the absence of dCF and AdR ('chase' experiment). Incubation with dCF and AdR resulted in a significant rise of dATP concentrations in all groups (the highest rises occurring in the leukaemic groups particularly in AML and Thy-ALL). The concentrations of the other three deoxyribonucleoside triphosphates fell in all groups. The dATP level fell during the 'chase' period but in Thy-ALL and thymocytes this fall was insignificant and slower than in the other groups. This suggests that not only intracellular build-up of dATP but also the capacity of the cell to degrade dATP is important for in vivo cytotoxicity of dCF treatment. These results help to explain the differences in response to dCF of the different leukaemias.
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A modification of the unlabeled antibody immunoperoxidase technic, using human antisera to identify blood group substances A and B in normal human colon is described. Overall, staining for the blood group substances is strongest in the cecum and proximal colon; there is a progressive reduction of staining for the blood group substances in the distal colon with almost complete loss in the recto-sigmoid area. The blood group substances are present in epithelial cells and in epithelial mucin, the most intense positive staining often being located in the supranuclear, Golgi region of the cells.
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The first quantitative measurements of the effect of metal substitution on (myo)globin conformational stability are reported. Metallomyoglobins examined include Fe(III), Cr(III), Rh(III), Mn(III), Fe(II), Zn(II), Cu(II), and Ru(II). It is shown that the protein denaturant interaction is not altered, in general, by metal substitution. Therefore reversible denaturation provides a means to assess the dependence of myoglobin conformational energy on metal electronic state. A simple relationship was found between the conformational free energy of trivalent metal derivatives (delta delta G0u) and the metal imidazole bond strength (delta Gim) of that derivative. Clear differences are observed between the divalent and trivalent metal derivatives, independent of delta Gim.
Biliary tract resistance was measured in 142 patients during cholecystectomy with the use of narcotic or nonnarcotic anesthesia techniques. If fentanyl citrate (narcotic) was used, there was no difference in the pressures measured in normal ducts between these cases and those patients receiving nonnarcotic anesthesia. When morphine sulfate was administered, the resistance exceeded normal values in five of seven patients with normal ducts.
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Three patients with granulomatous hepatitis due to cytomegalovirus are described. They are compared to the three previously described patients with this disease, and their clinical and serologic characteristics are discussed. Similarities and differences between infectious mononucleosis (Epstein-Barr virus) and cytomegalovirus infections are adduced. That cytomegalovirus may be a cause of granulomatous hepatitis in the adult is stressed.