The new H2-antagonists--are we prescribing them?
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Biomedical subjects
Publications and source records attributed to K Mills.
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Intestinal obstruction developed in a 4-month-old child in association with an ileal lymphangioma. Intestinal lymphangiomas have only rarely been reported in the literature. This case report documents an additional case and also points out an association with intestinal obstruction. The clinical and pathologic details of lymphangiomas are also reviewed.
Macrophages stimulated by various substances exhibit altered morphology, metabolism, and enhanced phagocytosis. The present studies were done to show if peroxidative enzymes would affect macrophage spreading and phagocytosis. Resident peritoneal macrophages, collected from C57BI mice were exposed to various concentrations of peroxidases and compared with appropriate controls. Results indicated that 0.01 microM myeloperoxidase (MyPO), 0.09 microM horseradish peroxidase (HRP), 0.16 microM lactoperoxidase (LPO) and 70 microM microperoxidase (MPO) significantly enhanced macrophage spreading. It was also noted that peroxidases were able to stimulate phagocytosis by increasing the number of cells with internalized zymosan at least twofold. Stimulation of these functions suggests a possible role of endogenous peroxidases as natural cell activators.
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Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency. Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier. Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice. The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals. The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes. AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi. By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells. Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals.
Amphotericin B is an efficacious but extremely toxic anti fungal drug. Recently it has been shown that the incorporation of Amphotericin B in multilamellar liposomes results in a marked reduction in drug toxicity in mice with no loss of anti fungal potency. Until now, the mechanistic basis of the enhanced therapeutic index of liposomal Amphotericin B has been unclear. In this report, however, we show that the in vivo effects can be mimicked in vitro where free but not liposomal Amphotericin B causes lysis of erythrocytes while both free and liposomal drug kill fungal cells. These results suggest that the markedly improved therapeutic index of liposomal Amphotericin B is largely due to a fundamental alteration in the ability of the drug to interact with mammalian cell membranes rather than to alterations in pharmacokinetics or drug distribution.
The in vitro activities of liposome-encapsulated amphotericin B and free amphotericin B against Candida albicans 336 were comparable. Amphotericin B concentrations 12-fold and greater than 50-fold higher were required to kill the same organism when cholesterol and ergosterol were incorporated into the liposomes. The addition of cholesterol to liposomes caused a significant increase in the minimal fungicidal concentration of amphotericin B in 7 of 19 other yeast strains tested, whereas ergosterol caused an increase in 18 of the 19 strains.
Bacteremia caused by newly described Campylobacter-like organisms occurred in two immunosuppressed homosexual patients with tuberculosis. Although these organisms grow well in aerobic bottles using a radiometric blood culture system, they are not readily seen in gram-stained smears and are easily missed if routine subculture methods are used. Microscopic examination of wet preparations and subculture to brucella agar base supplemented with 10% sheep blood and incubated in microaerophilic conditions are useful for identification and isolation. The recovery of Campylobacter-like organisms from the blood suggests that these organisms, formerly known only to be associated with proctocolitis or asymptomatic rectal infection in homosexual men, can also cause systemic infection in these patients.
A simple indirect rosette technique is described which allows the rapid enumeration, morphological identification and separation of monoclonal-antibody (MoAb)-defined human lymphocyte populations. The method is based on the binding to MoAb-stained cells of marker ox red blood cells coated with anti-mouse immunoglobulin. When compared with indirect immunofluorescence staining assessed by microscopy, the rosette method is quicker, shows greater sensitivity and is less subjective. Purification of helper (OKT4), suppressor (OKT8) or B-cell (BA1) subpopulations by positive or negative enrichment of rosetted cells gives purity and recoveries comparable with that of the fluorescence-activated cell sorter (FACS). Such purification is readily performed without loss of viability or function and is more easily done sterilely than with the FACS.
Several analogues (21 and 29-50) of exo-3-phenylbicyclo[3.2.1]oct-3-en-2-amine (1) were prepared, a compound that had been found to have marked antinociceptive activity in the inflamed-paw pressure test in rats. Two synthetically versatile methods leading to these compounds are described. In this series, antinociceptive activity increases with increasing size of the amine substituent, reaching an optimum with N(Me)Et (32), but this is always associated with central nervous system (CNS) stimulant activity. The antinociceptive activity of these compounds is most likely due to an action that is similar to that of amphetamine rather than to an interaction with an opiate receptor. The endo diastereoisomer 22 and the benzo analogue 11 were both devoid of antinociceptive and CNS stimulant activity.
The toxicology of liposome-encapsulated amphotericin B in mice and its efficacy in the treatment and prophylaxis of systemic candidiasis in these animals were studied. The toxicology studies indicated that the maximal tolerated dose of free amphotericin B was 0.8 mg/kg of body weight and the 50% lethal dose (LD50) was reached at 1.2 mg/kg, while neither the maximal tolerated dose nor the LD50 for the liposomal amphotericin B was reached at a dose of 12 mg/kg. No abnormalities in blood chemistry or histology were observed in the animals injected with encapsulated amphotericin B, while the administration of free amphotericin B was associated with nephrocalcinosis and renal parenchymal edema. The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B (4 mg/kg) had a longer survival time. Thus, an improved therapeutic index resulted by encapsulating amphotericin B in liposomes.
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Lysozyme was measured after 186 doses of methotrexate (MTX) to 88 patients. After 7.5% of the doses, lysozyme rose to between 2 and 19 micrograms/cc and in 3.2% it rose to between 20 and 120 micrograms/cc. These increases had no relationship to the age of the patients, their dose of MTX, the total number of times that MTX had been given, nor to rises in serum creatinine. It did correlate with the administration of aminoglycosides (a part of the supportive care of these patients) in two thirds of these cases. In patients who did not receive aminoglycosides, no urinary lysozyme concentration rose above 19 micrograms/cc, not even in the patients who became oliguric or required hemoperfusion. Most of these rises occurred early and were of 24 to 48 hour duration. The rises occurring after five days were persistent and were associated with prolonged MTX serum concentrations, suggesting that tubular damage due to MTX was the result of prolonged exposure to MTX, rather than the primary cause of kidney damage, i.e., the event causing the prolonged serum concentrations.
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A case of chondrosarcoma of the spine in a 45-year-old woman is described. The bone scan performed after the intravenous injection of Tc-99m-MDP not only confirmed the solitary nature of the tumor, but also demonstrated its extent within the spinous process of the second dorsal vertebra. Preoperative bone scan in the management of chondrosarcoma is advocated as a safe, noninvasive technique for assessing the extent of the tumor.