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Biomedical subjects

M Worthington

Publications and source records attributed to M Worthington.

At least 37 records · Page 2Linked to original sources

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.

Administration, Cutaneous↗

Zoladex versus danazol in the treatment of pelvic endometriosis: effects on plasma lipid risk factors.

Plasma lipid risk markers for coronary heart disease (CHD) are influenced by sex steroid concentrations. Therapies that alter sex hormone levels have the potential to affect CHD risk. Zoladex had no effect on plasma lipids, but increased high density lipoprotein (HDL) subfraction 3, a lipoprotein of uncertain clinical significance. Danazol increased low density lipoprotein and decreased HDL concentrations to give a lipid profile associated with increased risk of CHD.

Buserelin↗

3'-Azido-3'-deoxythymidine (AZT) inhibits proliferation in vitro of human haematopoietic progenitor cells.

Peripheral blood cytopenias are a serious, dose-limiting toxicity of AZT therapy in patients infected by HIV. To evaluate the mechanism by which cytopenias develop, AZT effects of haematopoietic differentiation and growth were measured in serum-free, nucleoside-depleted cultures of normal human bone marrow. In contrast to native thymidine, AZT suppressed the proliferation of erythroid, granulocyte/macrophage and primitive haematopoietic stem cells in a dose-related and time-dependent fashion. Relative progenitor sensitivity varied, with half-maximal concentrations of 1-5 microM and 20-40 microM AZT for inhibition of erythroid and nonerythroid progenitor cell growth, respectively. Inhibition was observed over full ranges of concentrations of haematopoietic tissue-specific regulators (human erythropoietin, colony-stimulating activity, interleukin-3 and lymphocyte conditioned medium) and of platelet-derived growth factor (PDGF), an agent that enhances erythropoiesis in vitro via accessory marrow stromal elements. Furthermore, suppression was similar in cultures of marrow cells that were depleted of accessory populations, suggesting that its action is directed at progenitors. Finally, when deoxythymidine was added in increasing amounts to cultures with a half-maximal concentration of AZT, inhibition was abrogated. We conclude that AZT is a potent inhibitor of haematopoiesis in vitro, and that erythroid progenitors are particularly sensitive to its action. These results may explain the marrow hypoplasia that occurs during AZT administration in vivo.

Antiviral Agents↗

Tricuspid valve myxoma infected with dysgonic fermenter-2.

We have described a patient with an infected myxoma attached to the tricuspid valve. Unlike those previously reported, our patient had a significant underlying disease, chronic lymphocytic leukemia, and presented the problem of multiple pulmonary infiltrates in an immunosuppressed host, with persistently negative blood cultures. The infecting bacterium, isolated only at operation, was a recently described fastidious gram-negative rod belonging to the CDC group dysgonic fermenter-2.

Bacterial Infections↗

Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation.

A 34-year-old man who used intravenous drugs developed the acquired immunodeficiency syndrome with lymphadenopathy, Mycobacterium tuberculosis pneumonia, and progressive multifocal leukoencephalopathy. Early biopsy specimens of the lymph node showed hyperplasia without evidence of lymphoma. Later, immunologic analysis of peripheral blood lymphocytes showed inversion of the helper/suppressor T-lymphocyte ratio and persistent monoclonal B-cell proliferation without clinically overt lymphoma. The clinical course of this patient suggests that abnormal immune responses seen in the setting of the acquired immunodeficiency syndrome may evolve into lymphoproliferative disorders detectable by peripheral blood lymphocyte analysis.

Acquired Immunodeficiency Syndrome↗

Acute chemical meningitis after metrizamide-lumbar myelography.

Severe acute meningitis developed after the use of metrizamide for lumbar myelography; cerebrospinal fluid findings included a white blood cell count of 2300, mostly polymorphonuclear cells, glucose level of 8 mg% and protein level of 253%. This apparent chemical meningitis could not be distinguished, either clinically or by cerebrospinal fluid examination, from acute bacterial meningitis. This case emphasizes that severe acute meningeal reactions, while very rare, can occur after the use of metrizamide for myelography. Such patients must be evaluated promptly to rule out bacterial meningitis and should be followed carefully for possible later sequelae.

Acute Disease↗

Fatal candida pneumonia in a non-immunosuppressed host.

An 83-year-old previously well non-immunosuppressed woman developed invasive fatal candida pneumonia, apparently caused by aspiration. Diagnosis was suggested by the presence of sheets of budding yeasts and pseudohyphae on Gram-stained expectorated sputum and confirmed by an open lung biopsy which demonstrated candida invading lung tissue. Culture of material obtained by open lung biopsy yielded Candida albicans. At autopsy the patient had extensively invasive bilateral candida pneumonia. No other pathogens were isolated from sputum, open lung biopsy or at the time of autopsy. Evidence of disseminated candidiasis was not seen at autopsy. To our knowledge, this is only the fourth documented case of aspiration candida pneumonia in a non-immunosuppressed adult. While candida pneumonia in an immunocompetent adult is very rare, it should be considered in an elderly patient who is not responding to antibiotic therapy. Diagnosis requires aspiration or biopsy of lung, with preferably both histological and cultural evidence of candida infection.

Adult↗

An in vitro RNA polymerase III system from S. cerevisiae: effects of deletions and point mutations upon SUP4 gene transcription.

A soluble cell-free extract containing RNA polymerase III and factors essential for selective transcription of the yeast SUP4-o tRNATyr gene was prepared from Saccharomyces cerevisiae cells. An intragenic promoter for yeast RNA polymerase III was identified within the yeast tRNATyr coding sequence by testing several sup4 genes with 5'- and 3'-terminal deletions in the homologous transcription system. Thirty-four different sup4 genes with spontaneous mutations were also tested in the in vitro system. Two point mutations drastically reduced transcription initiation and two other mutations caused premature termination. These mutations have nearly identical effects on SUP4 gene transcription by Xenopus RNA polymerase III (1), which demonstrates that the essential features of RNA polymerase III transcription initiation and termination signals have been conserved throughout the course of eukaryotic evolution.

Base Sequence↗

Influence of propranolol isomers and atenolol on myocardial cyclic AMP, high energy phosphates and vulnerability to fibrillation after coronary artery ligation in the isolated rat heart.

The isolated rat heart with ligation of the left coronary artery was used to assess the role of the beta 1- adrenergic receptor-cyclic AMP mechanism in the genesis of vulnerability to ventricular fibrillation in early myocardial ischaemia. Coronary artery ligation was followed after 3 min by a reduction in ventricular fibrillation threshold which reached a minimum at 15 min. This was accompanied by reduction of ATP and phosphocreatine while cyclic AMP was significantly increased in ischaemic myocardium. The dl-, l- and d-isomers of propranolol attenuated the decrease in ventricular fibrillation threshold and the increase in ischaemic myocardial cyclic AMP, without altering the tissue depletion of ATP. Specific beta 1-adrenergic receptor antagonism with atenolol did not prevent either the increase of tissue cyclic AMP or the reduction in ventricular fibrillation threshold and high energy phosphates. These findings suggest that the mechanism whereby vulnerability to fibrillation is increased in very early myocardial ischaemia is linked to changes in cyclic AMP content of ischaemic myocardium and appears independent of depletion of myocardial high energy phosphates.

Adenosine Triphosphate↗