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10,000,200 | Thrombocytopenia occurs frequently in newborn infants with sepsis, but the exact mechanism remains obscure in those infants who do not have evidence of disseminated intravascular coagulation. Since recent work has suggested a possible immune mechanism for thrombocytopenia observed in adults with sepsis, we have investigated the role of platelet-associated immunoglobulin in severe neonatal infections. To detect PAIgG we use a method employing protein A and peroxidase-antiperoxidase as a labeled antibody. PAIgG was quantitated by phase contrast microscopy and expressed as a reactive index. Our control group included 16 normal newborn infants whose mean RI was 0.65 +/- 0.01 SE. In addition to the control group, five infants with nonimmune thrombocytopenia were included; their mean RI was 0.66 +/- 0.01 SE. Seventeen newborn infants with severe infections were assayed for PAIgG. Eight of nine infants with bacterial infections had increased RI, with a mean of 1.16 +/- 0.03 SE (P less than 0.01). Six of the eight infants with viral infections had elevated RI, with a mean of 1.23 +/- 0.03 SE (P less than 0.01). These findings suggest that an immune mechanism may be involved in the thrombocytopenia of severe neonatal infection. | [
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10,000,201 | Clinical uses of platelets: a review. | [
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10,000,202 | Severe thrombocytopenia delays but does not prevent the occlusion of an arterial prosthesis in rats. | [
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10,000,203 | This study shows that experimentally-induced immune thrombocytopenia significantly delayed occlusion of an arterial prosthesis inserted in rat abdominal aorta. Thrombocytopenia was effective when induced several hours or shortly, or even several hours after the insertion of the prosthesis. Maintenance of severe thrombocytopenia by daily administrations of antiplatelet antiserum appeared to further delay thrombotic occlusion. However, though delayed, occlusion eventually occurred in all rats, even in those with very low platelet count. This would imply that any attempt to prevent arterial prosthesis thrombosis solely by interfering with platelets is ultimately bound to fail. | [
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10,000,204 | [Role of hormonal disorders in the etiology of polycystic ovary syndrome (Stein-Leventhal syndrome)]. | [
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10,000,205 | Hematopoiesis in the human spleen. | [
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10,000,206 | To assess the capacity of the human spleen to function as a hematopoietic organ, spleen mononuclear cells from patients undergoing splenectomy were cultured to assay CFU-E, BFU-E, and CFU-C. Although the peripheral blood from cases of hereditary spherocytosis, Gaucher disease, Thalassemia major, and idiopathic thrombocytopenic purpura yielded 3-20 BFU-E/5 X 10(5) cells plated and 1-7 CFU-C/5 X 10(5), suspensions of spleen cells failed to grow colonies. Histologically these spleens did not show extramedullary hematopoiesis. In contrast, peripheral blood from a patient with osteopetrosis (marble bone disease) yielded 130 BFU-E/5 X 10(5), 40 CFU-E/5 X 10(5), and 9 CFU-C/5 X 10(5). The spleen had extensive extramedullary hematopoiesis on microscopy and grew 180 BFU-E/10(5), 210 CFU-E/10(5), and 25 CFU-C/10(5). We conclude that spleens from patients without extramedullary hematopoiesis do not contain committed hematopoietic progenitors in spite of normal precursors in the blood. In osteopetrosis the spleen contained stem cells in a concentration comparable to bone marrow, and the embryonic role of the spleen in blood formation appeared to continue in postnatal life. | [
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10,000,207 | Studies on erythrocyte porphobilinogen deaminase and uroporphyrinogen cosynthetase in porphyria cutanea tarda. | [
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10,000,208 | The porphyrias: clinical chemistry, diagnosis and methodology. | [
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10,000,209 | Use of phenylbutazone in sports medicine: understanding the risks. | [
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10,000,210 | Despite the widespread use of phenylbutazone, its safety is still a controversial issue. One example of its toxicity is the fact that phenylbutazone has now replaced chloramphenicol as the most common cause of fatal drug-related aplastic anemia. To evaluate the toxicity of phenylbutazone as it is commonly used in sports medicine, a group of 3,000 healthy young athletes was studied following 1-week courses of phenylbutazone for various sports-related inflammatory problems. No serious adverse reactions were encountered. Four percent of the patients experienced mild gastrointestinal disturbances with less than 1% of the patients being forced to discontinue the medication. Compiling the results of other studies, it is estimated that the risk of a serious reaction to phenylbutazone is less than 1 per 100,000 when the drug is used by healthy young individuals for periods of 1 week or less. This risk increases significantly in older patients and with longer periods of treatment. Although phenylbutazone is widely prescribed in sports medicine, there appears to be insufficient information regarding its possible effects on athletic performance. Its capacity to cause significant fluid retention with secondary dilutional anemis, for example, could, in certain instances, have an adverse effect on overall performance if the drug is continued after the athlete returns to competition. Further study in this area is urged. | [
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10,000,211 | Microspectrofluorimetric estimation of the formaldehyde-induced fluorescence of the developing main pelvic ganglion of the rat. | [
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10,000,212 | The formaldehyde-induced fluorescence (FIF) of the cytoplasm of individual developing neurons of the main pelvic ganglion was recorded microspectrofluorimetrically in order to follow changes in catecholamine (noradrenaline) content during development. For each ganglion, the fluorescence intensity profile was estimated and shown graphically as columns expressing percentage distribution of relative intensities in different intensity classes. During development, the number of weakly fluorescent neurons increases. Treatment with testosterone shifts the profile towards higher intensities in four- and six-week-old animals. Testosterone affected the main pelvic ganglion but not the superior cervical ganglion. The intensity of the cytoplasmic FIF, which correlates with the catecholamine (noradrenaline) content of the object tissue, showed a tendency to decrease during development. This change was not obvious vy visual observation because of the increase in cell size and the toal bulk of the ganglion. Other possible factors affecting visual observation are discussed. | [
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10,000,213 | [Interaction with completely fluctuationally opened base pairs is not the only pathway for formaldehyde reaction with DNA]. | [
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10,000,214 | Onycholysis secondary to toluene sulfonamide formaldehyde resin used in a nail hardener mimicking onychomycosis. | [
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10,000,215 | Kinetics of hydrolysis of methenamine. | [
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10,000,216 | The kinetics of degradation of methenamine were studied in citrate--phosphate buffers between pH 2.0 and 7.4 at 37.5 degrees. GLC was used to monitor the rate of hydrolysis. The conversion of methenamine to formaldehyde was found to be pH dependent in the buffers of constant ionic strength, with the reaction half-life decreasing from 13.8 hr at pH 5.8 to 1.6 hr at pH 2.0. The kinetics of degradation also were measured at 47, 57, and 67 degrees, and the reaction obeyed the Arrhenius relationship. At pH 2.0, the activation energy was calculated to be 23.5 kcal/mole; at pH 5.1, it was 12.0 kcal/mole. | [
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10,000,217 | Release of serotonin from human platelets in vitro by radiographic contrast media. | [
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10,000,218 | Both ionic and nonionic, monomeric and dimeric contrast media were found to release serotonin from intact human platelets in vitro. The monomeric contrast media were compared at the concentration range of 25 mg I/ml. Iothalamate was the strongest and the statistically equal metrizamide iopamidol, and P-297 were the weakest releasers. Monomeric and dimeric contrast media were compared at concentration ranges of 50 and 100 mg I/ml. They ranked, in descending order of serotonin releasing potency: iodipamide, iothalamate, P-127, iopamidol, and a statistically indistinguishable group of the monoacid dimer P-286, the nonionic dimer ZK 74 435, and metrizamide. The capability of contrast media to release serotonin seems to be a composite result of their specific physical and molecular structural properties. | [
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10,000,219 | Relationship between formaldehyde-related antibodies and cross-reacting anti-N-like antibodies in patients undergoing chronic haemodialysis. | [
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10,000,220 | An attempt was made to determine the sequence of events leading to the production of two distinct antibodies in patients with chronic renal failure who regularly undergo haemodialysis with formaldehyde-resterilizable dialysis units by Multipoint (UK) or Cordis (USA). A distinct pattern emerged-namely, the production of anti-formaldehyde red cells started about six months after the beginning of haemodialysis treatment. Only when the titre of these antibodies reached 64 or 128 another, apparently cross-reacting, antibody appeared which reacted like an anti-N antibody. A strong direct antiglobulin reaction was found to be positive for formalin-treated red cells after five minutes' contact with specific antibody, indicating a high affinity of the antibody fo the formalin-altered red cell. | [
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10,000,221 | [Hygienic evaluation of phenol-formaldehyde construction materials used for building agricultural structures]. | [
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10,000,222 | N-Nitroso compounds from reactions of nitrite with methylamine. | [
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10,000,223 | [Disinfection and sterilization of artificial pulmonary ventilation apparatus]. | [
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10,000,224 | Stability of formalin test solutions. | [
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10,000,225 | The role of the macrophage in in vitro primary anti-DNP antibody production in man. | [
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10,000,226 | Combined autoradiography and formaldehyde-induced fluorescence methods for localization of radioactively labeled substances in relation to monoamine neurons. | [
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10,000,227 | A combined technique of formaldehyde-induced fluorescence (FIF) and autoradiography is described for the localization of radioactively labeled substances in relation to monoamine neurons. This method permits the simultaneous visualization of 3H-labeled steroid hormone or drug uptake sites and fluorescing monoamine neural elements (cell bodies, fiber projections, terminals) in the same tissue section. Thin frozen sections cut in a cryostat are freeze-dried, exposed to formaldehyde vapor at 80 degrees C, and carried through dry-mount autoradiography processing steps before fluorescence microscopy screening. Subsequent histological staining of sections and light microscopy are employed for conventional autoradiogram screening. With this procedure, 3H-estradiol and 3H-dihydrotestosterone are localized in various catecholamine (CA) neurons in the diencephalon and lower brain stem of the rat. Also, catecholaminergic as well as noncatecholaminergic sex steroid target neurons are seen to be innervated by CA terminals in various rat brain regions. | [
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10,000,228 | Formaldehyde sensitivity and toxicity. | [
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10,000,229 | Effects of concentration-dependent plasma protein binding on ceftriaxone kinetics. | [
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10,000,230 | The kinetics of ceftriaxone, a cephalosporin, was studied in six healthy subjects who received bolus injections of 150, 500, and 1,500 mg intravenously in a random crossover fashion. Although total drug concentration time profiles after all doses could be described by biexponential equation, simple compartment analysis was inappropriate because a disproportional increase in the area under the total drug concentration time curves occurred with dose. This resulted in a dose-dependent increase in total systemic clearance (ClTS) from 9.7 ml/min at the 150-mg dose to 13 ml/min at the 1500-mg dose. The dose-dependent changes in ClTS could be explained in terms of the concentration-dependent plasma protein binding of ceftriaxone (fplasma ranging from 0.04 to 0.167), because the area under the free drug concentration time curves (AUCFO-infinity) increased proportionately to dose. Mean total clearance with reference to free (unbound) ceftriaxone (ClFS) was constant at 255 ml/min. Calculated mean renal clearance with reference to free ceftriaxone (ClFR) was 173 ml/min, or slightly more than the average glomerular filtration rate in humans. Mean plasma ceftriaxone t1/2 was not influenced by dose and averaged 8 hr. This biological t1/2 is by far the longest ever for a cephalosporin in healthy subjects. | [
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0.101249... |
10,000,231 | Paradoxical sleep deprivation and performance of an active avoidance task: impairment of c57BR mice and no effect in c57BL/6 mice. | [
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0.03530959412455559,
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10,000,232 | [Comparative study of Faust et al. and Ritchie methods for parasitological examinations of feces]. | [
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10,000,233 | A monoclonal antibody-inhibiting FMLP-induced chemotaxis of human neutrophils. | [
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10,000,234 | A monoclonal IgG1 antibody, termed NCD3, was raised against human neutrophils and has been shown to inhibit neutrophil chemotaxis. NCD3 displayed a considerable degree of stimulus specificity in that it inhibited N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced chemotaxis up to 80%, C5a and zymosan-activated plasma induced chemotaxis by only 20% and had no effect on leukotriene B4- (LTB4) or casein-mediated chemotaxis. NCD3 did not inhibit granule enzyme release from neutrophils in response to stimulation by various secretagogues, including FMLP, in the presence or absence of cytochalasin B (CB). Neutrophil phagocytosis of 51Cr-labeled opsonized sheep erythrocytes (51Cr-EAC) and superoxide anion (O2-) production in response to FMLP or phorbol myristate acetate (PMA) stimulation were not affected by pretreating cells with NCD3. Divalency of NCD3 was necessary for inhibition of chemotaxis, suggesting a requirement for cross-linking of the antigenic determinants on the neutrophil membrane surface. | [
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10,000,235 | An introduction to current controversies in cancer management: stage I testicular cancer-a case in point. | [
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0.058892... |
10,000,236 | Optimal management of clinical stage I nonseminomatous testicular carcinoma: one oncologist's view. | [
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0.0257543046... |
10,000,237 | Prophylactic antimetastatic treatment with aryldimethyltriazenes as adjuvants to surgical tumor removal in mice bearing Lewis lung carcinoma. | [
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10,000,238 | The effects of two benzenoid dimethyltriazenes (1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt [DM-COOK] and 1-p-tolyl-3,3-dimethyltriazene), which have been previously shown to reduce the formation of spontaneous lung metastases in mice bearing subcutaneous Lewis lung carcinoma, have been investigated in mice implanted im with the same tumor in the calf of the hind leg. Primary tumor was removed surgically by amputation in mice treated with the tested compounds preoperatively, and the survival time of the animals was then determined. A high rate of cures, ranging from 23% to 43%, has been observed when the treatment consisted of eight or three daily doses prior to tumor removal; a single immediately preoperative dose was less effective and caused a 10% cure rate. Survival time of uncured mice was also significantly increased, particularly by DM-COOK. The division of the dose into two daily injections did not modify the activity of the triazenes, thus indicating that the antimetastatic coverage between two subsequent doses is not limited by fast pharmacokinetics or decomposition of the drugs. These results show that, at least in one animal system, aryldimethyltriazenes can be used also on palpable tumors as prophylactic adjuvants to surgery in order to reduce preoperative and intraoperative tumor spread. | [
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10,000,239 | Doxorubicin cytotoxicity enhanced by local anesthetics in a human melanoma cell line. | [
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10,000,240 | Local anesthetics may influence cell membrane structure and permeability. An established human melanoma cell line (SHG) derived from malignant ascites was used to evaluate the growth-inhibitory effects of local anesthetics (procaine and lidocaine) as well as of doxorubicin at incubation temperatures of 37.5 degrees C and 40 degrees C. In this system, procaine and lidocaine inhibited growth at 0.82 mg/ml and doxorubicin inhibited growth at 28 ng/ml. Noninhibitory concentrations of procaine (0.64 mg/ml) when combined with noninhibitory concentrations of doxorubicin (10 ng/ml) resulted in marked growth inhibition. Incubating temperatures of 40 degrees C enhanced all effects of procaine and doxorubicin on cell growth. These results suggest that clinically achievable concentrations of local anesthetics enhance doxorubicin cytotoxicity. | [
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10,000,241 | Adsorption of antineoplastic drugs following large-volume ip administration to rats. | [
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0.025573... |
10,000,242 | Clinical stage I testis tumors: the medical oncologist's view. | [
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0.013570447... |
10,000,243 | Local and systemic toxicity resulting from large-volume ip administration of doxorubicin in the rat. | [
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10,000,244 | Doxorubicin was administered to rats in a simulated "belly bath" protocol. Fifty milliliters of various concentrations of drug solution was administered ip and was allowed to remain in situ for either 4 or 36 hours prior to removal. Animals were analyzed at 2, 14, and 60 days after treatment. Doses ranged from lethal (75 and 150 micrograms/ml for 4 hours; 12 and 24 micrograms/ml for 36 hours) to nontoxic (5 micrograms/ml for 4 hours). The most common lesion in surviving animals was chronic fibrosing peritonitis. Grossly, there were large volumes of peritoneal fluid in animals exposed to low concentrations (12 and 24 micrograms/ml) for 36 hours, but peritoneal adhesions were the most commonly observed finding when higher concentrations (20-150 micrograms/ml) were used for 4 hours. Commonly observed systemic toxic effects (bone marrow, gastrointestinal tract, and heart) were not seen in this study. Vehicle-treated control animals were negative for all histologic lesions and gross observations. | [
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0.15189... |
10,000,245 | Combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) in TNM-classified stage IV mycosis fungoides. | [
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10,000,246 | Nine patients with stage IV mycosis fungoides (MF), according to TNM classification, were treated with cyclophosphamide, vincristine, and prednisone (CVP). CVP induced a 66% overall objective response rate and a 44% complete response rate, which is the highest reported in the literature. CVP is an effective regimen in MF and could be employed in combination with total skin or total lymphoid radiotherapy. TNM classification should be used for all patients with MF, because it makes the evaluation and comparison of treatments more reliable. | [
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10,000,247 | Phase II study of divided-dose vinblastine in non-small cell bronchogenic carcinoma. | [
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0.0160066... |
10,000,248 | A role for vinblastine (VBL) in lung cancer has never been clearly defined. Because of recent pharmacokinetic data suggesting a biweekly schedule for VBL and recent antitumor activity shown for vindesine, a phase II trial of divided-dose VBL was initiated. Among 22 evaluable patients, a 27% major response rate was seen, with a median duration of 5.5 months (range 3.5-12+). The major toxic effect was myelosuppression but was easily manageable and tolerated. These results suggest schedule dependency for VBL and open the question of its efficacy in lung cancer. | [
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10,000,249 | Phase I trial of spirogermanium given by infusion in a multiple-dose schedule. | [
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0.047164... |
10,000,250 | In a phase I study of spirogermanium, a new azaspiran-germanium compound, 28 patients were given a multiple-dose schedule. When infused over 1 hour, the maximum tolerated single dose of this agent was greater than 120 mg/m2 but significant chronic neurologic toxicity occurred after 1-2 weeks of treatment. Patients with a poor performance status (PS) were the most likely to manifest toxic reactions. Suggested phage II dose levels for infusion treatment with spirogermanium are 120 mg/m2 for patients with a PS of 0-2 and 80 mg/m2 for patients with a PS of 3. | [
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0.0863055... |
10,000,251 | Phase II study of doxorubicin and mitomycin in non-small cell bronchogenic carcinoma. | [
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10,000,252 | Thirty patients with advanced measurable non-small cell bronchogenic carcinoma were treated with a combination of doxorubicin (50 mg/m2 every 3 weeks) and mitomycin (20 mg/m2 every 6 weeks). One complete and three partial responses were observed. This response rate is similar to that reported for either drug used alone. | [
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0.0475637130... |
10,000,253 | Disposition of indicine N-oxide in mice and monkeys. | [
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0.087169... |
10,000,254 | The disposition of tritium-labeled indicine N-oxide (INO) was evaluated in mice and rhesus monkeys. Disappearance of INO from the serum of BDF1 mice given iv doses of 100 or 500 mg/kg occurred with an initial half-life of about 11 mins followed by a second phase greater than 100 mins. At 2 hrs after iv injection of mice, the highest concentrations of INO were present in kidney, liver, and intestine. In CDF1 mice bearing P388 leukemia cells and injected ip with a dose of 500 mg/kg, INO was found, in equal concentrations, in cells of the parent line, which is resistant to INO, and in cells of a line resistant to cyclophosphamide but sensitive to INO. Serum levels of INO in these mice decreased with an initial half-life of about 20 mins. For monkeys given iv doses of 24, 2.4 of 0.24 mg/kg, INO disappeared from the serum in three phases, with average half-lives of 3, 32, and 180 mins, respectively. Half-lives for the two observed phases of urinary excretion were 40 and 240 mins. In 24 hrs, both mice and monkeys excreted greater than 80% of the doses unchanged. | [
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0.... |
10,000,255 | Phase II trial of mitolactol in patients with metastatic melanoma. | [
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0.0... |
10,000,256 | Combination chemotherapy for bronchogenic carcinoma with doxorubicin, BCNU, and cyclophosphamide (ABC): a pilot study of the Southeastern Cancer Study Group. | [
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0.006065906025469303,
0.13796275854110718,
-0.0235224... |
10,000,257 | Prednimustine in advanced soft tissue sarcomas. | [
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0.04932952672243118,
0.0497836209833622,
0.05884... |
10,000,258 | Phase II study of high-dose intermittent cycloleucine in colorectal malignancies. | [
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0.011691738851368427,
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0.10094493627548218,
0.0160... |
10,000,259 | Is there a relation between previous tuberculosis and long-term survival after solid tumor chemotherapy? | [
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0.1111588403582573,
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0.011312... |
10,000,260 | Proper analysis of clinical trials for malignant glioma. | [
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10,000,261 | Elevation of plasma antidiuretic hormones (ADH) associated with chemotherapy-induced emesis in man. | [
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10,000,262 | Eleven randomly hydrated patients with metastatic malignancies received iv bolus chemotherapy. Serial observations of plasma antidiuretic hormone (ADH), serum osmolality, blood pressure, and presence of nausea or emesis were made over the next 3-4 hours. Group 1 (four patients) had no nausea or emesis and no change in ADH, osmolality, or mean blood pressure. Group 2 (seven patients) had nausea and emesis following chemotherapy, with an increase in mean ADH from a baseline level of 5.53 pg/ml to a peak after emesis of 33.83 pg/ml. Group 2 had no significant increase in osmolality or decrease in mean blood pressure before emesis. ADH levels increased 0-40 minutes before emesis and peaked 28-115 minutes (mean, 66) after emesis. Emesis caused by chemotherapy agents is associated with rapid, significant increases in plasma ADH levels, independent of changes in osmolality or blood pressure. | [
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10,000,263 | Nonparametric confidence limits for survival probabilities and median survival time. | [
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10,000,264 | Comparison of the use of teniposide and vincristine in combination chemotherapy for non-Hodgkin's lymphoma. | [
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10,000,265 | A total of 164 patients with non-Hodgkin's lymphoma (NHL) were randomized to receive cycles of treatment every 3 weeks with either CTP, ie, cyclophosphamide (400 mg/m2/day orally X 5), teniposide (VM-26) (100 mg/m2 iv X 1), and prednisolone (60 mg/m2/day orally X 5), or COP, ie, vincristine (1.4 mg/m2 iv X 1; maximum, 2 mg) with the same cyclophosphamide and prednisolone doses listed above. Results were analyzed according to whether the patients' NHL histology was favorable (47 patients) or unfavorable (117). The great majority of patients in each group had advanced disease (stage IV in 70% and stage III in 20%). For each histologic group, the results with the two regimens were similar with respect to remission incidence and survival. In favorable-histology NHL, CTP produced 57% complete remissions (CR) and 29% partial remissions (PR), compared with 54% CR and 19% PR for COP. Survival in these patients was also similar for the two regimens, the relative death rates being 1.13 for CTP-treated patients and 0.88 for COP-treated patients (P = 0.75). In patients with unfavorable-histology NHL, CTP produced 38% CR and 28% PR, compared with 43% CR and 35% PR for COP, the relative death rates being 1.10 for CTP-treated patients and 0.90 for COP-treated patients (P = 0.49). Neurotoxicity was virtually absent in patients treated with CTP, whereas in COP-treated patients it was severe in 12% and moderate in 36%. Other toxic effects occurred with equivalent frequency in the two regimens. These results show that teniposide can replace vincristine in combination with cyclophosphamide and prednisolone in the treatment of NHL, with freedom from neurotoxicity and comparable survival and response rates. | [
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10,000,266 | Surgical treatment of clinical stage I nonseminomatous germ gell tumors of the testis. | [
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10,000,267 | The rationale for further treatment after orchiectomy and the logical basis of the principle therapeutic alternatives in the management of clinical state I nonseminomatous germ cell tumors of the testis have been reviewed. Retroperitoneal lymph node dissection provides the epitome of staging accuracy and a high degree of therapeutic effectiveness in clinical stage I nonseminomatous germ cell tumors of the testis and is associated with minimal early and late morbidity and a low mortality. However, all methods of further active therapy after radical orchiectomy are under legitimate scrutiny in view of the burden of unnecessary therapy, the accuracy of clinical staging, the ability to recognize failures early, and the high probability of successful treatment of such failures. | [
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10,000,268 | Doxorubicin, mitomycin, and 5-FU (DMF) in the treatment of hormone-resistant stage D prostate cancer: a preliminary report. | [
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10,000,269 | Fifteen patients with advanced stage D hormone-resistant prostate cancer were treated with the combination of doxorubicin, mitomycin, and 5-FU. Nine patients (60%) had objective responses, with a mean duration of 27.9 weeks. No responding patient had relapsed. Although three patients developed a culture-negative leukopenic fever, no deaths from chemotherapy occurred. Preliminary results with doxorubicin, mitomycin, and 5-FU indicate that this is a very effective chemotherapy regimen, resulting in a high objective response rate in metastatic prostate cancer. | [
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10,000,270 | Methyl-GAG in patients with malignant neoplasms: a phase I re-evaluation. | [
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10,000,271 | Methyl-GAG was given to 71 patients with advanced malignancies as a weekly brief infusion (30-120 minutes) or as a biweekly 24- or 120-hour infusion. Mucositis (stomatitis, pharyngitis, esophagitis, and, rarely, inflammation of other mucous membranes) was dose-limiting in all three schedules. Generalized fatigue, malaise, myalgia, dysesthesias, nausea, and vomiting were more frequent in the brief-infusion schedule. Myelosuppression was mild and not dose-related. Fever, ventricular arrhythmias, skin rash, tender swelling of the palms, neuropathy, and paralytic ileus were rare. Toxicity was increased in patients with renal insufficiency or "third-space" fluid but was not increased by hepatic dysfunction. Cumulative and overlapping toxicity was evident only in the weekly schedule. Higher doses of methyl-GAG were tolerated when the duration of infusion was increased. The recommended doses for phase II trials are 700 mg/m2 weekly as a 1-2 hour infusion, 850 mg/m2/24 hours biweekly, and 1500 mg/m2/120 hours biweekly. Therapeutic effects were seen in all schedules and included objective responses in colon carcinoma (one of 13 patients), renal cell carcinoma (one of nine), and Hodgkin's lymphoma (one of two) and objective improvements in esophageal carcinoma (one of three), endometrial carcinoma (two of two), and leiomyosarcoma (one of three). | [
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10,000,272 | Phase I study of L-alanosine using a daily x 3 schedule. | [
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10,000,273 | L-Alanosine is an antitumor antibiotic that inhibits adenine synthesis. It showed significant activity in animal tumor systems. Using a daily x 3 dose schedule every 3 weeks, we performed a phase I study to determine toxicity in man. Doses of 8-375 mg/m2/day x 3 were administered to 49 patients in 117 courses. The dose-limiting toxic effect was mucositis. Vomiting, infrequent myelosuppression, fever, headache, malaise, and blood pressure changes were detected at higher dose levels. No antitumor activity was noted. Toxicity with this regimen is acceptable. A phase II study with doses of 250 mg/m2/day x 3 every 3 weeks is feasible. | [
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10,000,274 | Pilot study of PALA and 5-FU in patients with advanced cancer. | [
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10,000,275 | A pilot study was carried out among 21 patients with advanced solid tumors to establish appropriate dose levels of PALA and 5-FU given on a 5-day schedule to produce definite but tolerable clinical toxicity. While dermatitis, diarrhea, leukopenia, and thrombocytopenia were observed, stomatitis was the dose-limiting side effect. The recommended initial dose levels for further clinical trials are 625 mg/m2 of PALA daily x 5 and 250-300 mg/m2 of 5-FU daily x 5, with courses repeated at 4-week intervals. Studies were also conducted to establish the time course of anticipated increased incorporation of 5-FU into cellular RNA following treatment with PALA. In murine P388 leukemia, PALA increased tritiated 5-FU incorporation by as much as 70%, the effect being maximal within 1 hour and maintained up to 25 hours. It was not possible to demonstrate increased tritiated 5-FU uptake into normal human leukocyte RNA from patients receiving combination chemotherapy with PALA and 5-FU, perhaps because of low rates of RNA synthesis. | [
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10,000,276 | Phase I trial and pharmacokinetics of a daily x 5 schedule of 3-deazauridine. | [
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10,000,277 | The uridine analog 3-deazauridine has been given to 19 patients in a phase I and pharmacokinetic study. Only mild toxicity was seen at doses less than 1200 mg/m2/day for 5 days. At a dose of 1200 mg/m2/day x 5, leukopenia (mean wbc count nadir of 2650/mm3) was seen in nine of 12 patients and thrombocytopenia (mean platelet count nadir of 47,000/mm3) in five of 12 patients. Nausea and vomiting and oral toxicity were each seen in two patients, and diarrhea and skin toxicity occurred in one patient each. Pharmacokinetic studies indicate a biphasic plasma decay with a beta-half-life of 6.9 hours and urinary excretion, mostly of unchanged drug, as the most important route for drug elimination. A dose of 1200 mg/m2/day x 5 is recommended for phase II studies and great caution is advised in administering the drug in the presence of renal impairment. | [
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10,000,278 | Effect of malnutrition on methotrexate toxicity and tissue levels of dihydrofolate reductase in the rat. | [
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10,000,279 | The effect of malnutrition on the toxicity of methotrexate (MTX) and the dihydrofolate reductase (DHFR) content of the liver, small intestinal mucosa, kidney, and bone marrow of male Sprague-Dawley rats was studied. Malnutrition was induced by reducing the daily intake of chow to one third for 14 days. A single ip treatment with MTX was lethal to three of nine rats at a dose of 37.5 mg/kg and to three of five rats at a dose of 50.0 mg/kg but caused only transient weight loss to similarly treated full-fed, age-matched controls. Although the body weights and absolute tissue weights were reduced in malnourished rats, only the liver and small intestinal mucosa were smaller relative to their respective body weights. The cellular DHFR content of liver and bone marrow from malnourished rats was lower than that from the controls, although in terms of the content per gram of tissue, there was no significant change. While the total DHFR in malnourished rat tissues was significantly lower than that for the controls, only the total-liver DHFR was lower relative to the body weight. The increased toxicity of MTX to malnourished rats may be related to the DHFR levels in the liver and bone marrow. | [
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10,000,280 | Vinylogous carbinolamine tumor inhibitors. 8. Activity of bis(acyloxymethyl) derivatives of pyrroles and pyrrolizines against a panel of murine leukemias and solid tumors. | [
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10,000,281 | The activity of three pyrroles and four pyrrolizines is compared in several different experimental leukemias and solid tumors in mice. Two compounds were particularly noteworthy, the bis(N-cyclohexylcarbamate) and the bis[N-(2-propyl)] derivatives of 2,3-dihydro-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-1H-pyrrolizine. These two compounds showed a very high level of activity against B16 melanocarcinoma, CD8F1 mammary tumor, colon tumor 26, and colon tumor 38, and a significant number of "cures" were recorded. The isopropyl compound was more potent than the cyclohexyl compound, but both showed a similar profile of activity. | [
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10,000,282 | Pulmonary blood volume ratio response to exercise; a noninvasive determination of exercise-induced changes in pulmonary capillary wedge pressure. | [
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10,000,283 | Independent contribution of electrocardiographic abnormalities to risk of death from coronary heart disease, cardiovascular diseases and all causes. Findings of three Chicago epidemiologic studies. | [
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10,000,284 | Epicardial activation in patients with coronary artery disease: effects of regional contraction abnormalities. | [
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10,000,285 | Intramyocardial conduction: a major determinant of R-wave amplitude during acute myocardial ischemia. | [
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0.000711096334271133,
0.10884... |
10,000,286 | Two-dimensional echocardiographic features of right ventricular infarction. | [
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10,000,287 | Real-time, two-dimensional echocardiographic studies were performed in 10 patients with acute myocardial infarction who had clinical features suggestive of right ventricular involvement. All patients showed right ventricular wall motion abnormalities. In the four-chamber view, seven patients showed akinesis of the entire right ventricular diaphragmatic wall and three showed akinesis of segments of the diaphragmatic wall. Segmental dyskinetic areas involving the right ventricular free wall were identified in four patients. One patient showed a large right ventricular apical aneurysm. Other echocardiographic features included enlargement of the right ventricle in eight cases, paradoxical ventricular septal motion in seven cases, tricuspid incompetence in eight cases, dilatation of the stomach in four cases and localized pericardial effusion in two cases. Right ventricular infarction was confirmed by radionuclide in seven patients, at surgery in one patient and at autopsy in two patients. | [
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0.0586... |
10,000,288 | Verapamil versus placebo in relieving stable angina pectoris. | [
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0.0290... |
10,000,289 | Verapamil and placebo were compared in patients with stable, effort-induced angina. Single-blind dose titration (240, 360 and 480 mg/day) preceded a double-blind crossover. Among the 18 patients who completed graded exercise stress tests with reproducible pretreatment effort-limiting angina, exercise duration increased from 348 +/- 127 seconds (SD) before treatment to 494 +/- 182 seconds after verapamil (p less than 0.001), but did not change after placebo. Compared with placebo, verapamil reduced the weekly number of anginal episodes from 4.54 +/- 5.03 to 2.44 +/- 3.30 (p less than 0.05) and reduced nitroglycerin consumption from 3.46 +/- 5.30 to 1.55 +/- 2.89 tablets per week (p less than 0.05). Of 26 patients who completed the single-blind dose titration, 16 were improved (greater than 1 minute) at a dosage of 240 or 360 mg/day. No patient improved (greater than 1 minute) on 480 mg/day who had not already improved on a lower dose, but side effects requiring reduction in dosage occurred in seven patients receiving 480 mg of verapamil per day. Verapamil is an effective antianginal drug that appears most efficacious at a dose of 360 mg/day, but side effects are common at a dose of 480 mg/day. | [
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10,000,290 | Evaluation of combined valvular prolapse syndrome by two-dimensional echocardiography. | [
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10,000,291 | The patterns of aortic and tricuspid valve motion in 50 patients with mitral valve prolapse were analyzed by wide-angle, phased-array, two-dimensional echocardiography. Twelve patients (24%) had redundant aortic leaflets bulging into the left ventricular outflow tract during diastole. Eight of 12 patients had aortic regurgitation and seven of 12 had M-mode echocardiographic evidence of aortic valve prolapse. One patient underwent mitral and aortic valve replacement, and the excised valves revealed marked myxomatous degeneration. Eight of 15 patients undergoing contrast echocardiography had tricuspid regurgitation (systolic reflux of contrast material into the inferior vena cava persisting for more than 10 beats), and prolapse in the septal leaflet of the anterior leaflet or both. A similar tricuspid valve pattern was noted in three of seven patients without tricuspid regurgitation. Tricuspid valve prolapse was identified in 20 patients (40%). Nine patients (18%) had combined prolapse of the mitral, aortic and tricuspid valves. In five patients with middiastolic high-pitched murmurs recorded along the left sternal border, tricuspid valve prolapse was demonstrated. In one of these patients, the presence of pulmonary regurgitation was confirmed by intracardiac phonocardiography. We conclude that two-dimensional echocardiography is useful for evaluating patients with combined valvular prolapse syndrome. | [
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10,000,292 | Arterial dilators in mitral regurgitation: effects on rest and exercise hemodynamics and long-term clinical follow-up. | [
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10,000,293 | Determinants and clinical significance of jugular venous valve competence. | [
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10,000,294 | We studied the function of right internal jugular vein valves during cardiac catheterization in 32 patients and external jugular vein valves in vitro from 13 dogs. Patients with normal central venous pressure had competent valves during cough-induced transvalvular pressure gradients of 52.4 +/- 8.6 mm Hg. Ten of 15 patients with elevated central venous pressure had either incompetent or absent internal jugular valves, the latter occurring only in patients with long-standing, severe tricuspid regurgitation. During coughing, competent valves were also demonstrated in the left internal jugular and in the right and left subclavian veins. The excised canine valves were competent at a static transvalvular pressure of 81.8 +/- 3.7 mm Hg. Five of six excised valves remained competent during pulsatile transvalvular pressure of 64.8 +/- 1.9 mm Hg. Thus, thoracic inlet venous valves are usually competent during sudden increases in intrathoracic pressure. These valves may play an important role in establishing the extrathoracic arteriovenous pressure gradient necessary for forward blood flow during cardiopulmonary resuscitation and other states with high intrathoracic pressure. | [
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10,000,295 | Stereoselective interaction of sulfinpyrazone with racemic warfarin and its separated enantiomorphs in man. | [
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10,000,296 | Although serious hemorrhage during therapeutic coadministration of sulfinpyrazone and racemic warfarin occurs, no prospective studies have been done. In this study, single oral doses of racemic warfarin, 1.5 mg/kg, were administered to six normal subjects with and without oral sulfinpyrazone, 400 mg daily. Both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.05) were significantly augmented. To determine if this interaction was stereoselective, the experiments were repeated in the same subjects with R-and S-warfarin enantiomorphs. S-warfarin with sulfinpyrazone caused a highly significant augmentation of both the hypoprothrombinemia (p less than 0.001) and the plasma warfarin concentrations (p less than 0.001). R-warfarin with sulfinpyrazone did not significantly change the hypoprothrombinemia but significantly (p less than 0.05) reduced warfarin concentrations. Thus, sulfinpyrazone augmented the hypoprothrombinemia of racemic warfarin stereoselectively by reduced metabolic clearance of S-warfarin. Sulfinpyrazone and racemic warfarin are most dangerous when either drug is added to a stabilized regimen of the other drug. | [
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10,000,297 | Secondary prevention in myocardial infarction survivors. | [
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0.0117799... |
10,000,298 | The 24-hour ambulatory blood pressure profile with verapamil. | [
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10,000,299 | The blood pressure response in hypertensive subjects to chronic treatment with verapamil, a calcium antagonist (or, more precisely, a slow-channel inhibitor), was studied using the Oxford system for continuous monitoring of intraarterial blood pressure. Sixteen patients underwent continuous monitoring over a 48-hour period before and after at least 6 weeks of therapy (dose range 120-160 mg three times daily). Each monitoring period included physiologic tests designed to show the effects of different types of exercise. Verapamil produces a consistent reduction of blood pressure over 24 hours, but particularly during the day. Heart rate was similarly reduced. There was no evidence of postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. The degree of reduction of the blood pressure was consistent, suggesting that slow-channel inhibitors may be appropriate for antihypertensive therapy. | [
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0.02377868816256523,
0.009276586584746838,
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0.0392... |
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