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Biomedical subjects

F Johnson

Publications and source records attributed to F Johnson.

At least 145 records · Page 8Linked to original sources

Vacuum extraction versus forceps delivery: indications and complications, 1979 to 1984.

Two hundred fifty-six vacuum extractions and 300 randomly chosen forceps deliveries were analyzed retrospectively. Vacuum extraction use increased from 0.3 to 3.1%, while forceps use declined from 10.1 to 4.9% over a five-year period. No differences were found in indications for vacuum extraction and forceps, but the preapplication position differed (occiput posterior or transverse in 81.2% in the vacuum group and 27% in forceps patients). Preapplication station also differed, with 59.8% of vacuum extraction at +1 or higher stations, compared with 9% of forceps. Under these conditions we found less maternal trauma, similar failure rates (3.9 versus 2%), and no difference in maternal morbidity. There was a higher incidence of shoulder dystocia and neonatal jaundice in the vacuum group, but cephalohematoma frequency did not differ significantly (3.9% vacuum extraction, 4.3% forceps). Cosmetic injuries (ecchymoses, abrasions) were more likely with vacuum extraction than with forceps (44.1 versus 29.5%). One death occurred in each group. Vacuum extraction replaced midforceps in our institution in the study period. We consider vacuum extraction a useful technique to teach house staff in view of today's decreasing instrumental delivery rate.

Birth Injuries↗

Streptonigrin. 1. Structure-activity relationships among simple bicyclic analogues. Rate dependence of DNA degradation on quinone reduction potential.

A series of simple aza and diaza bicyclic quinones related to the AB ring system of streptonigrin (1) have been synthesized and tested in vitro for their ability to degrade DNA under conditions similar to those used with the parent drug. The results obtained from a study of 22 quinones indicate that there is a quantitative linear relationship between their reduction potentials and the rate at which they degrade DNA under identical conditions in vitro. Almost all of the synthetic substances were superior to 1 in their DNA-degrading ability.

DNA↗

Femoral head shape in Perthes' disease. Is the contralateral hip abnormal?

Femoral head shape has been assessed in 47 children with unilateral Perthes' disease and 41 control children. Measurements were taken from radiographs and arthrographs by a computerized method. In controls the femoral head was round, particularly in lateral outline, and characteristically asymmetric in anteroposterior views at all ages studied. In children with Perthes' disease the bony femoral head was less round than in controls and flattened anteriorly. Mediolateral symmetry differed from that of controls, reflecting lateral flattening of the cross section of the femoral epiphysis. Age-related changes correlated with disease duration but not with treatment. The "unaffected" hip showed some evidence of anterior and lateral flattening from the time of diagnosis of disease in the other hip. No subject developed bilateral disease during the follow-up period. This early involvement of the "unaffected" hip could indicate a constitutional abnormality. The cartilaginous femoral head was rounder than the underlying bony epiphysis, particularly in anteroposterior views. The cartilage of the hip with Perthes' disease was less round than that on the "unaffected" side. There was no evidence of anterior or lateral flattening of either cartilaginous femoral head.

Adolescent↗

Origin and cytotoxic properties of base propenals derived from DNA.

Base propenals arise from DNA by a Fe(II)-bleomycin-mediated reaction which leads to strand scission. These compounds undergo addition-elimination reactions with thiols and other nucleophilic groups under physiological conditions and form an addition product with glutathione. Thymine- and adenine-N1-propenals inhibit DNA synthesis in HeLa cells; both compounds are cytotoxic [50% inhibiting concentration (IC50) = 1 to 2 microM]. A structurally related nucleoside, thymidine-N3-propenal, designed as a metabolic pathway inhibitor, inhibits growth of HeLa, L1210 leukemia, Lewis lung carcinoma, B16 melanoma, and DLD-1 human colon carcinoma cells in culture (IC50 = 1 to 6 microM). A single injection of this compound, administered on the first day following transplant of L1210 leukemia cells, increased the mean survival time of mice by 50% (T/C = 154). Thymidine-N3-propenal selectively blocks DNA synthesis in HeLa cells and inhibits thymidine kinase (Ki = 5.1 microM) and DNA polymerase-alpha. We suggest that base propenals, rather than damaged DNA, account for some of the cytotoxic effects of bleomycin and that nucleoside propenals represent a novel class of site-directed inhibitors.

Antineoplastic Agents↗

Electrocautery: effects on steroid receptors in human breast cancer.

The determination of steroid receptors in human breast cancers has assumed increasing importance over the past several decades. Improper handling of the specimens could affect results obtained. This study details the effects excessive levels of heat that occur with the use of electrocautery can have on steroid receptor quantities and localization. Twelve resected primary and metastatic human breast cancers were analyzed for cytoplasmic and nuclear receptors by biochemical analysis. In addition, steroid binding was determined by direct fluorescent histochemical techniques. To a portion of each resected specimen a Boviec was applied to simulate electrocautery resection. Analysis of the different portions of the same tumor revealed that there was a decrease in measurable cytoplasmic receptor in all cauterized specimens and a concomitant increase in the nuclear receptor. A similar shift in steroid binding was noted in all the specimens analyzed by fluorescent histochemical techniques. The results of this study show that the application of excessive heat to human breast cancers will lead to false negative biochemical steroid receptor determination by shifting the receptors intranuclear.

Breast Neoplasms↗

A simple method of measuring aqueous humor flow with intravitreal fluoresceinated dextrans.

Fluoresceinated dextran was injected into the vitreous cavity of rabbits and its concentration was followed in the vitreous and aqueous humors for a period of weeks by slip-lamp fluorometry. The concentrations in both fluids fell in parallel and in an exponential manner where the time constant was determined by the molecular weight of the dextran. The rate of movement of the dextran from the vitreous into the anterior chamber is controlled by passive diffusion and may be assumed to be relatively steady; accordingly, the faster the rate of flow in the aqueous humor the lower will be the concentration of dextran in it. Circadian variations in the aqueous flow were observed, a drop at night time being noted. These were small enough for changes due to systemic influences to be determined; in particular, it was found that general anesthesia with ketamine had no significant effect. The ratio of the concentration in the anterior chambers of the two eyes of one animal normally remains constant with time. Changes in the ratio can be used to determine the influence of unilateral interventions. This was illustrated by the use of adrenergic drops which led to a brief rise in flow rate and then a longer-lasting fall, and by X-ray irradiation with 1000 rads, which caused an immediate fall in flow rate interrupted for a time by a phase of increased flow. An absolute estimate of the aqueous flow can be derived from measurements of the total amount of dextran in the eye and its concentration in the anterior chamber. A definite value has not yet been established owing to ambiguities in determining the former quantity.

Anesthesia, General↗

Synthesis and biological activity of a new class of cytotoxic agents: N-(3-oxoprop-1-enyl)-substituted pyrimidines and purines.

The 1-(3-oxoprop-1-enyl) derivatives of thymine and cytosine and the corresponding 9-substituted derivatives of adenine and guanine (products of degradation of DNA by bleomycin, Fe2+, and O2) have been synthesized and tested for biological activity. The thymine and adenine compounds are highly cytotoxic to a variety of tumor cell lines and inhibit macromolecular synthesis in cultured HeLa cells. Structure-activity studies, based primarily on the pyrimidine derivatives, reveal that the most potent inhibition occurs when the propenal group is located on the 3-nitrogen of a 2'-deoxyribonucleoside. The 3-(3-oxoprop-1-enyl) derivatives of thymidine, 2'-deoxyuridine, and 5-iodo-2'-deoxyuridine powerfully and selectively inhibit incorporation of thymidine into DNA at concentrations (IC50 approximately equal to 0.5 microM) comparable to those observed with idoxuridine. Active compounds in this series react readily with nucleophiles containing primary amino and sulfhydryl groups. The results of this study provide a basis for the development of a new class of cytotoxic agents.

Aldehydes↗

Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route.

The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Animals↗

Rhodamine B as a test molecule in intraocular dynamics.

Rhodamine B is a lipid-soluble, nontoxic dye that fluoresces at longer wavelengths than fluorescein and consequently is detectable at lower concentrations in the ocular tissues. Its dynamics after topical and systemic administration are similar to those of lipid-soluble drugs.

Animals↗

Drug interactions I: detection of inorganic nitrite in organic nitrate esters under acidic conditions simulating the human stomach.

Both unformulated (bulk) and formulated (drugs) organic nitrate esters (isosorbide dinitrate, nitroglycerin, and pentaerythritol tetranitrate) were studied in the presence and absence of hydrochloric acid to determine if they could be sources of nitrite (and therefore lead to nitrosamine formation) under acidic conditions similar to those found in the stomach. The presence and generation of nitrite ion was detected by a modification of the Griess reaction. Bulk isosorbide dinitrate and nitroglycerin were found to be contaminated with 13.8-121.4 mumoles of inorganic nitrite per mole of nitrate ester. In addition, in the presence of hydrochloric acid, these preparations generated 0.52-1.18 mumoles of inorganic nitrite/mole of nitrate ester/min. Unformulated nitroglycerin generated nitrite at a rate roughly twice that of isosorbide dinitrate. In contrast, no evidence for nitrite contamination or generation by pentaerythritol tetranitrate was found. Tablets and capsules of isosorbide dinitrate contained approximately 27-216 mumoles of nitrite/mole of nitrate ester and, in the presence of hydrochloric acid, generated an average of 0.55 mumole nitrite/min. For isosorbide dinitrate, this rate was similar for bulk and formulated drug. In comparison to isosorbide dinitrate, the amount of nitrite initially present in tablets and capsules of nitroglycerin varied more widely (approximately 25-2290 mumoles nitrite/mole of nitrate ester), and in this case nitrite was generated at higher rates than unformulated drug averaging approximately 4.7 mumoles nitrite/mole of nitrate ester/min. Contrary to a literature report, we found that nitrate ion is not reduced to nitrite by hydrochloric acid (pH 1-3).(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Pharmaceutical↗

Groups for parents of children with Down's Syndrome and multiple handicaps: a pilot project.

One of the main purposes of an Infant Stimulation Program is to assist parents in finding ways of adjusting to and developing the potential of the handicapped child. The Peel Infant Stimulation program at the Mississauga Hospital in Mississauga, Ontario, while aptly fulfilling this purpose, noted that in some instances the stress of having a handicapped child added tension to the marital relationship. In addition, some parents appeared to have difficulty recovering from the news of their child's condition. In response to these observations a consultant with expertise in groups, couples, and family therapy was hired to help form groups for parents who appeared to be having difficulties. An Occupational Therapist from the Infant Stimulation Program was trained in group leadership while co-leading the groups with the consultant. The article explores the rationale for the groups, describes the sessions, and discusses a number of issues that are pertinent to the running of the groups. The intent of the article is to encourage staff working in similar programs to investigate the use of parent groups.

Down Syndrome↗