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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 505 records · Page 28Linked to original sources
PubMed1985

Phase I trial of misonidazole (NSC#261037) plus cyclophosphamide in solid tumors.

Misonidazole, a hypoxic cell sensitizer, enhances the antitumor effects of cyclophosphamide in preclinical studies. Several studies also showed increased cytotoxicity for normal tissues. We undertook a phase I study of this combination. The regimen consisted of oral administration of misonidazole at one of two dose levels, 1 g/m2 and 2 g/m2, followed by an intravenous (IV) injection of cyclophosphamide four hours later. The cycle was repeated every twenty-one days. The dose of misonidazole remained constant for each regimen, but the dose of cyclophosphamide ranged from 0.4 g/m2 to 1.3 g/m2. Thirty-eight trials in 35 patients with advanced solid tumors were considered evaluable. Dose-limiting toxicity was granulocytopenia at 1 g/m2 of cyclophosphamide without significant thrombocytopenia or anemia. Peripheral neuropathy was negligible. Two patients received cumulative doses of 8 and 16 g/m2 of misonidazole without neurotoxicity. One patient developed hemorrhagic cystitis. Nausea and vomiting was mild to moderate. Possible evidence of tumor stabilization was seen in three patients, and one patient had a mixed response. The mean serum half-life for misonidazole was 11.3 hours (range, 8.4 to 20.0) and for cyclophosphamide 8.3 hours (range, 3.2 to 15.5), both within the previously reported ranges. In conclusion, it appears that this combination is well tolerated and that misonidazole does not significantly potentiate myelotoxicity caused by cyclophosphamide or alter its pharmacokinetics. The recommended starting doses for misonidazole and cyclophosphamide in phase II trials using this schedule of administration should be 2 g/m2 and 1 g/m2, respectively, with escalation for cyclophosphamide to individual tolerance.

Adult↗
PubMed1985

Application of a tissue culture microtiter test for the detection of cytotoxic agents from natural products.

A method is described by which the growth inhibitory effects of cytotoxic compounds and fermentation broth cultures on adherent tumor cell lines can be quantitated. Cells are seeded into 96-well microtiter plates and 16 hours later the test compounds or broths are added to the wells. Cell growth is measured after three days (B16 mouse melanoma cells) or six days (HT-29, human colon carcinoma cells) by first fixing adherent cells, staining with Giemsa stain, washing away excess stain, then solubilizing stained cells with HCl. Absorbance is determined using a microELISA spectrophotometer and the data are transferred to and analyzed by a computer. The assay is rapid and reproducible and can be used to identify fermentation broths with cytotoxic components. Addition of DNA into the assay mixture (cells plus compound) inhibits the cytotoxic activities of certain DNA-reactive agents. The results of this study demonstrate the application of this assay system for primary and secondary evaluation of fermentation broths for in vitro antitumor activity.

Animals↗
PubMed1985

Upper abdominal lymphadenopathy as first presentation of relapse, identified by ultrasonography, in patients treated for small cell (oat cell) bronchogenic carcinoma.

Ten patients treated for 'limited' stage small cell lung cancer presented during follow-up with epigastric or back pain together with nausea and/or vomiting. Upper abdominal lymphadenopathy was shown to be the first symptomatic site of relapse. A single fraction of radiotherapy provided a convenient, effective form of palliation. Ultrasound scanning proved an accurate, readily available technique for the diagnosis of this form of intra-abdominal disease.

Abdomen↗
PubMed1985

Physician compliance with colorectal cancer screening (1978-1983): the impact of flexible sigmoidoscopy.

Physician compliance with widely recommended colorectal cancer screening methods was studied over a five-year period in a university-based family medicine residency program. Indicated examinations were being avoided in symptomatic as well as asymptomatic patients aged over 50 years. The introduction of flexible sigmoidoscopy created significant change in previously documented poor resident and faculty compliance. Baseline measurement of outcomes was noted by audit of 189 adult medical records (year 1). Educational reemphasis by lecture and intragroup commitment produced no change by the end of year 2 (n = 189). Introduction of the flexible sigmoidoscope yielded a sevenfold increase in physician compliance in year 3 (n = 192). This compliance increased as measured by chart audit in years 4 (n = 166) and 5 (n = 190). All audited groups were mutually exclusive. The documented diagnostic superiority of this instrument was readily obtainable by family physician faculty and residents in training. With Papanicolaou smear activity serving as a control group, the findings indicated a significant and sustained effect. Two additional primary care training programs were audited during the final year of the study period. These control audits revealed continued poor compliance with rigid sigmoidoscopy. The flexible sigmoidoscope is an important addition to the diagnostic and screening armamentarium of a family medicine residency program.

Adult↗
PubMed1985

Activity of JM9 in advanced ovarian cancer: a phase I-II trial.

Thirty-nine patients with advanced solid tumors, including 28 with ovarian cancer, were entered in a phase I-II trial of a new platinum analog, JM9. Twenty-three patients had received prior chemotherapy which did not include cisplatin. Based on preliminary information from an ongoing study, our starting dose was 180 mg/m2. The total dose of JM9 was administered in 1 L of saline infused over 1 hour, with no additional hydration or electrolyte supplementation. Courses were repeated at 3-week intervals or after full recovery from thrombocytopenia. One hundred thirty-nine courses (range, one to six per patient) were administered at four dose levels: 180 mg/m2 (13 courses); 240 mg/m2 (64 courses); 300 mg/m2 (45 courses); and 350 mg/m2 (17 courses). The dose-limiting toxic effect was thrombocytopenia, which was dose-related and cumulative. Median platelet count nadirs were 50, 47, 25, and 28 X 10(9)/L for previously treated patients at dose levels of 180, 240, 300, and 350 mg/m2, respectively. For patients who had not received prior chemotherapy, the corresponding values were 403, 61, 44, and 36 X 10(9)/L. The nadir was predictable at Day 14 with recovery by Day 21 in earlier courses, but with delay of recovery to Days 28-42 in later courses and at higher dose levels. Twenty-five courses of chemotherapy in 15 patients were associated with a platelet count nadir of less than 20 X 10(9)/L, but despite this, serious hemorrhage was rare. Leukopenia was dose-related and mild; the median wbc count (X 10(9)/L) was 2.2 (range, 1.0-7.3) at the highest dose level of 350 mg/m2. The leukocyte count nadir was later than that for the platelet count (Days 21-28), and recovery was often not complete by the time of retreatment. All patients showed a progressive rise in mean corpuscular volume in successive courses, often accompanied by a fall in hemoglobin. Transfusions were required in 14 patients, 12 of whom had received prior chemotherapy. Nausea and vomiting, starting within 1 hour of drug administration, occurred in all patients, but appeared to be less severe and prolonged compared to that occurring with cisplatin. Diarrhea occurred in most patients at the two higher dose levels. There was no evidence of significant renal impairment, electrolyte disturbance, hearing loss, or peripheral neuropathy. Two patients had mild allergic reactions shortly after drug infusion and two others developed vasculitic rashes which were self-limiting.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Amyloidosis in six dairy cows.

Amyloidosis was diagnosed in 6 Holstein cows that were examined because of chronic intractable diarrhea. Besides diarrhea, the chief finding was a nephrotic-like syndrome, in that there was edema, hypoproteinemia, and proteinuria. Other consistent clinicopathologic abnormalities were hyperfibrinogenemia, low-normal serum calcium content or hypocalcemia, hypomagnesemia, prolonged bromosulphalein half time, high serum urea nitrogen concentration, high serum creatinine concentration, and low urine specific gravity. Foci of inflammation including traumatic reticuloperitonitis, traumatic pericarditis, salpingitis, mastitis, and metritis were found. There was histologic evidence of amyloid in the kidneys, liver, adrenal glands, and spleen. The iodine-sulfuric acid test for amyloid was positive in 2 cows. The Congo red dye test for amyloid was positive in 2 other cows. In spite of supportive care, all the cows either died naturally or were euthanatized. Because foci of inflammation were found in each cow, it was concluded that the most likely classification of amyloidosis in these cases would be reactive systemic amyloidosis and that the major amyloid fibril protein would be type AA.

Amyloid↗
PubMed1984

Administration of intravenous alcohol for prevention of withdrawal in alcoholic burn patients.

We studied the effects of intravenous alcohol infusions on 22 alcoholic burn patients admitted to our burn center. The relationship of infusion rates to blood alcohol levels was studied over a 3 to 8 day period of administration, and daily blood test results in liver function were followed. No patients had signs of withdrawal either during the infusion period or after the discontinuation of alcohol therapy. Our data suggest that the intravenous infusion of ethanol at rates of 0.02 to 0.06 g/kg per hour provides low but measurable blood alcohol levels (2 to 8 mg/100 ml), avoids sedation and toxic effects, and prevents the appearance of withdrawal symptoms in severely alcoholic burn patients.

Adolescent↗
PubMed1984

Use of a new chemically modified intravenous IgG preparation in severe primary humoral immunodeficiency: clinical efficacy and attempts to individualize dosage.

Sixteen patients with severe primary humoral immunodeficiency diseases were treated intravenously for 12 months with a beta-propiolactone stabilized preparation of IgG (Intraglobin) as part of a phase II study of safety and efficacy. In order to evaluate the metabolism of IgG in these patients and to determine whether increased doses of IgG would lead to a decrease in the rate of infections, the study was divided into two periods. All patients were infused with a standard dose of 100 mg/kg/month for 6 months and the peak and trough serum IgG concentrations were determined. The half-life of the IgG was determined in each patient after the fourth month and this value was used to calculate the dose necessary to raise the trough serum IgG concentration to a minimum of 200 mg/dl. The patients received this individualized dose in the final 6 months and the half-life determination was repeated at the conclusion of the study. Only 3 of 10 patients who received a higher dose in the second period had a substantial increase in trough serum IgG concentrations, but the failure to achieve higher concentrations was not due to a shortening of the half-life. The Intraglobin was well tolerated with no patient unable to complete the study due to side-effects. Ten percent of the infusions were associated with minor, self-limited reactions, with 16 of the 19 reactions occurring in the first 6 months. There were no life-threatening infections during the 12-month period. A total of 105 episodes of infections were recorded, but only a cumulative total of 51 days of normal school or work activity were lost by the 16 patients during the 12 months of the trial period. Most infectious episodes were due to chronic bronchitis, sinusitis, and otitis. There was no reduction in the number of infections in the second, higher dose period of the study; however, as there was little increase in serum IgG concentration, more data are required before it will be possible to determine if the incidence of chronic infections can be reduced by a further increase in the serum IgG concentration.

Adolescent↗
PubMed1984

Plasma and red cell levels of thioridazine and clinical response in schizophrenia.

The relationship of plasma and red blood cell (RBC) levels of thioridazine to clinical response in schizophrenia was evaluated in a fixed-dose study. Steady-state plasma and RBC levels of thioridazine, mesoridazine, and sum of thioridazine and mesoridazine, determined by gas-liquid chromatography, were not significantly correlated with clinical response as measured by improvement on the Brief Psychiatric Rating Scale. RBC thioridazine levels were not substantially more strongly correlated with clinical response than plasma levels.

Adult↗