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Biomedical subjects

E McDonald

Publications and source records attributed to E McDonald.

At least 55 records · Page 3Linked to original sources

Synthesis and antitumour activities of quinolone antineoplastic agents.

DNA topoisomerases, found in all prokaryotic and eukaryotic cells, play a key role in controlling the topological state of DNA. Quinolone antibacterial agents have been shown to be inhibitors of DNA gyrase, a bacterial topoisomerase II enzyme. The eukaryotic topoisomerase II is the target of various cytotoxic agents such as adriamycin and etoposide. Recently, several quinolones having C-8 fluoro and C-8 chloro substituents have been found to have cytotoxic activities and to interact with mammalian topoisomerase II. In searching for an antitumour agent of the quinolone class, we identified several quinolones having excellent in vitro cytotoxic activity. A-74932 also possesses good activity in vivo against both systemic tumour and subcutaneously implanted murine solid tumours as well as human tumour xenografts. The chemical synthesis as well as biological properties of A-74932 are described.

Animals↗

Gangrene of the fingers secondary to myeloproliferative disease.

The myeloproliferative disorders comprise a group of related diseases, including polycythemia vera, essential thrombocythemia, chronic myelogenous leukemia, myelofibrosis, and myeloid metaplasia. An increase in circulating platelets is associated with thrombotic phenomena affecting the arterial and venous circulation. In this article, the authors describe a case in which the initial manifestation of myeloproliferative disease was gangrene of the fingers.

Aged↗

Osteoarthritis and rheumatoid arthritis in elderly patients. Differentiation and treatment.

Osteoarthritis is differentiated from rheumatoid arthritis by age at onset, duration of morning stiffness, pattern of joint involvement, and radiographic findings. Distinguishing between the diseases can be challenging, because they have some symptoms in common. Therapy for osteoarthritis is aimed at relief of symptoms; treatment of active rheumatoid arthritis is more aggressive, aimed at controlling or modifying the disease. Both diseases may cause great pain and disability in elderly patients, so prompt diagnosis and treatment are essential.

Aged↗

Seborrheic dermatitis in acquired immunodeficiency syndrome.

Cutaneous eruptions are commonly seen in acquired immunodeficiency syndrome (AIDS). Seborrheic dermatitis in this patient population is usually more severe and difficult to diagnose and treat. The butterfly distribution of the rash and the interpretation of the biopsy may suggest a diagnosis of discoid lupus erythematosus, unless the pathologist is aware of the underlying immunodeficiency. We present two cases of patients with documented acquired immunodeficiency syndrome whose initial biopsies were interpreted as discoid lupus but whose cutaneous seborrheic dermatitis actually paralleled human immunodeficiency virus disease activity.

Acquired Immunodeficiency Syndrome↗

Oral acyclovir for chickenpox.

We report on our experience with acyclovir (Zovirax) capsules for the symptomatic treatment of chickenpox in two children and an adult.

Acyclovir↗

Dry mouth: diagnosing and treating its multiple causes.

Dry mouth in the elderly is a common occurrence with multiple etiologies. It is not a normal phenomenon of aging and, therefore, an attempt at elucidating its cause should be made. Sjögren's syndrome may occur, and it is diagnosed by labial biopsy. Medications are also frequently associated with dry mouth, and dosages may need to be adjusted or the drug discontinued if symptoms are severe. Strategies for management of dry mouth are explored.

Aged↗

Tired, weak, or in need of rest: fatigue among general practice attenders.

OBJECTIVES: To determine the prevalence and associations of symptoms of fatigue. DESIGN: Questionnaire survey. SETTING: London general practice. PARTICIPANTS: 611 General practice attenders. MAIN OUTCOME MEASURES: Scores on a fatigue questionnaire and reasons given for fatigue. RESULTS: 10.2% Of men (17/167) and 10.6% of women (47/444) had substantial fatigue for one month or more. Age, occupation, and marital status exerted minor effects. Subjects attributed fatigue equally to physical and non-physical causes. Physical ill health, including viral infection, was associated with more severe fatigue. Women rather than men blamed family responsibilities for their fatigue. The profile of persistent fatigue did not differ from that of short duration. Only one person met criteria for the chronic fatigue syndrome. CONCLUSIONS: Fatigue is a common complaint among general practice attenders and can be severe. Patients may attribute this to physical, psychological, and social stress.

Adult↗

Rheumatoid arthritis in a patient with sickle cell disease.

Sickle cell disease has various articular manifestations. Coexistent rheumatoid arthritis (RA) and sickle cell disease has been reported rarely. We present a patient with sickle cell disease and seropositive erosive RA demonstrating characteristic radiographic findings of the 2 entities.

Anemia, Sickle Cell↗

Fertility desires and fertility: hers, his, and theirs.

The relationship between desired and achieved fertility may be misspecified by excluding husbands' fertility desires or by confounding effects of shared desires with the resolution of conflicting desires. Using couple data from the classic Princeton Fertility Surveys, we find relatively large husband effects on fertility outcomes as well as unique effects of spousal disagreement. Wives and husbands were equally likely to achieve fertility desires, and disagreeing couples experienced fertility rates midway between couples who wanted the same smaller or larger number of children. These conditions do not hold, however, when we include willingness to delay births for economic mobility as part of the measure of fertility desires. Among couples who both wanted a third child, only husbands' willingness to delay births had significant negative effects on birth rates.

Birth Rate↗

Amyotrophic lateral sclerosis severity scale.

The amyotrophic lateral sclerosis (ALS) severity scale has been developed to provide an ordinal staging system and a means of rapid functional assessment for patients with ALS. The scale allows an examiner to evaluate the symptoms of ALS numerically in four categories that describe speech, swallowing, lower extremity, and upper extremity abilities. These scores, combined with a vital capacity measured on a hand-held respirometer, provide a rapid, accurate assessment of a patient's disease status and can be used for treatment planning. The ALS severity scale has been shown to have an average estimated reliability coefficient of 0.95 between examiners. Speech ratings were correlated greater than 0.80 for objective speech measures. Rates of progression of the total score in a small group of patients ranged from -3.4 to -24.0 points/year with a mean of -11.3 points/year.

Adult↗

Susceptibility testing of macrolide antibiotics against Haemophilus influenzae and correlation of in vitro results with in vivo efficacy in a mouse septicemia model.

There is poor correlation between the MICs and zone sizes obtained for erythromycin against Haemophilus influenzae. The effect of two media, Mueller-Hinton medium supplemented with 3% lysed horse blood and 10 micrograms of NAD per ml (MHA + LYHB) and Mueller-Hinton agar supplemented with 1% bovine hemoglobin and 1% IsoVitaleX (MHA + HGB), on the MICs and zone sizes of erythromycin against H. influenzae was determined. The effect of three different methods for inoculum preparation on the susceptibility of H. influenzae was also determined. The MICs were independent of the method of inoculum preparation, but the zone sizes were smaller if the inoculum was carefully adjusted to contain approximately 10(8) CFU/ml. MICs were higher and zone sizes were smaller when MHA + HGB was used instead of MHA + LYHB. Good correlation was found when MHA + LYHB was used for determining the MIC and MHA + HGB was used for determining susceptibility by the disk method. When the inoculum was adjusted to match a McFarland 0.5 standard, the viable counts had to be approximately 10(8) CFU/ml for good correlation between MICs and zone sizes. A-56268, a new macrolide antibiotic, was tested against H. influenzae, and its MICs and tentative breakpoints against this organism were determined. The MICs obtained by various methods were correlated with in vivo efficacy by using a mouse septicemia model. MICs obtained on MHA + HGB or MHA + LYHB incubated without a 5% CO2 atmosphere showed the best correlation with in vivo efficacy.

Animals↗

The action of natural and synthetic isomers of quisqualic acid at a well-defined glutamatergic synapse.

L-, D- and DL-quisqualic acid have been synthesized and their activities at the glutamatergic locust nerve-muscle junction have been compared with those of natural quisqualic acid and with glutamic acid. Two well-characterised locust nerve-muscle preparations were used in these studies, the retractor unguis nerve-muscle system and the extensor tibiae nerve-muscle system. The amino acids were tested on the whole nerve-muscle system in the former, when reduction in neurally evoked twitch contraction amplitude was the measured parameter, and by ionophoretic application to single excitatory junctional sites in the latter, when amplitude of junctional depolarization was the measured parameter. Synthetic L-quisqualic acid exhibited identical potency to its natural counterpart. However, D-quisqualic acid and DL-quisqualic acid were more active than expected from the known stereospecificity of this glutamatergic system towards D- and L-glutamic acid. The hydantoin analogue of quisqualic acid was inactive. X-ray crystallographic analysis of L-quisqualic acid and the hydantoin analogue showed that the ring junction in the former is pyramidal whereas in the latter it is planar. This may account for the high potency of L-quisqualic acid on a receptor system which identifies a partially folded conformation of L-glutamic acid. A pyramidal configuration of D-quisqualic acid would allow either rapid interconversion between active and inactive configurations at its ring junction or adoption of a trigonal configuration in solution. Either interpretation could explain the unexpected potency of D-quisqualic acid.

Animals↗

In vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide.

The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.

Administration, Oral↗

Occurrence of Cryptosporidium oocysts in fecal samples submitted for routine microbiological examination.

During a 7-month period, 2,252 fecal samples submitted for routine microbiological examination from 1,621 patients were screened for Cryptosporidium oocysts by the auramine staining method with Kinyoun acid-fast stain as the confirmatory stain. Cryptosporidium oocysts were detected in fecal samples from 19 (1.2%) patients, 18 of whom had gastroenteritis. Diarrheic stools from 14 of these 18 patients were negative for the usual enteropathogens but contained the oocysts in moderate to large numbers. Although Cryptosporidium oocysts were found in patients of all ages, they occurred slightly more frequently in infants and children than in the rest. Cryptosporidium species was one of the common enteropathogens identified in fecal samples submitted for routine parasitological examination during the period of the survey and was second only to Giardia species in terms of frequency. Considering cryptosporidiosis in the differential diagnosis of gastroenteritis in immunocompetent persons and including a search for Cryptosporidium oocysts in routine parasitological examinations of fecal samples appear warranted.

Adolescent↗