Biomedical subjects
Publications and source records attributed to D G Martin.
Cell culture techniques and antimicrobial systems can be used as detection systems for new antibiotic structures. Antimicrobial systems by virtue of their speed, economy, ease of use, and adaptation to chromatographic (bioautographic) techniques are definitely superior for assay and for dereplication purposes. A prescreen assay system which combines the advantages and minimizes the disadvantages of the two approaches is described.
By utilizing new types of producing microorganisms and isolating these on rather unusual growth media, we hope to produce new classes of antitumor drugs. In the detection system, we included the highly sensitive L1210 in vitro assay. But be requiring additional antimicrobial activity, we were able to eliminate rather early most of the previously known drugs from further work-up. The screening protocol was arranged so as to detect antimetabolites of a few rationally selected compounds.
A new antitumor antibiotic is produced in fermentation liquors of Streptomyces zelensis sp.n. The antibiotic is biologically active at extremely low concentrations. At 40 pg/ml, it inhibited 90% of the growth of L1210 cells in culture in tube dilution assays. The minimal inhibitory concentrations against Gram-positive bacteria is between 1 approximately 10 ng/ml, while these values for Gram-negative bacteria and fungi are mostly under 1 microgram/ml. A microbiological assay with Bacillus subtilis can detect concentrations of 1 approximately 2 ng/ml.
A case of meningoencephalitis caused by histoplasmosis in a renal transplant patient is described. The diagnosis was made postmortem. The clinicopathological features of 39 additional cases of central nervous system (CNS) invasion by histoplasmosis were reviewed. In the great majority of instances (92.1%), CNS involvement occurred in the disseminated form of the disease. Diagnosis was proved by culturing the fungus from bone marrow, blood, lymph nodes, or liver. Neurological symptoms and signs and cerebrospinal fluid (CSF) changes did not occur until extensive brain damage had resulted. Difficulty in culturing the organism in the (CSF) caused a further delay in making an early diagnosis of CNS involvement. The use of meningeal and brain biopsy specimens in conjunction with the electroencephalogram (EEG) may help in making an earlier diagnosis of CNS involvement.
Renal artery stenosis occurred in eight of fifty patients who received a renal transplant during a three year period. The evaluation and management of these cases is summarized. Trauma associated with kidney procurement, preservation, or arterial anastomosis as well as the rejection process itself may contribute to the development of these lesions. Arteriography may be indicated at an earlier stage in patients who respond poorly to medical treatment of repeated episodes of "rejection."
In a 52-year-old man with chronic renal failure, severe angina occured when he was receiving hemodialysis. A double coronary bypass graft was performed, providing complete relief.
Improved fermentation and isolation procedures for antitumor antimetabolites U-42,126 and U-43,795 increased drug yields 30-fold. The sensitivity limit of a newly developed assay is 0.03 mug of U-42,126 and 2.0 mug of U-43,795 per ml. The in vitro antimicrobial effect of both drugs was antagonized by histidine.
When polyurethane foam test tube plugs are autoclaved, they release volatile fatty amines that inhibit the growth of some microorganisms. The chemical structures of these amines were determined by the use of a gas chromatograph-mass spectrometer. They are catalysts used to produce the foam. The problem of contaminating growth media with toxic substances released from polymeric materials is discussed.
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Four uremic patients on maintenance hemodialysis developed intractable heart failure and atrioventricular block. All had persistently high (over 60) calcium-phosphorus products. At autopsy, all had metastatic myocardial calcification. Their inability to take phosphate-binding agents orally is responsible for this fatal complication.
In fifteen patients with severe hypertension, eight of whom had end-stage kidney disease, blood pressure could not be adequately controlled with conventional oral antihypertensive drugs. Minoxidil, an orally administered drug which lowers blood pressure by reducing total peripheral resistance, produced a substantial reduction in blood pressure in all patients who were treated, including patients who prior to its availiability would have been considered for bilateral nephrectomy.
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