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Biomedical subjects

P R Watson

Publications and source records attributed to P R Watson.

29 records · Page 2Linked to original sources

The Salmonella dublin virulence plasmid mediates systemic but not enteric phases of salmonellosis in cattle.

Plasmid-bearing and plasmid-free isolates and a plasmid-cured strain of Salmonella dublin were compared for virulence in calves. The plasmid-bearing strains were highly virulent, causing severe enteric and systemic disease with high mortality. In contrast, the plasmid-free strains caused diarrhea but only low mortality. The infection kinetics of a wild-type and a derivative plasmid-cured strain were compared. Both strains were isolated in high numbers from intestinal sites at 3 and 6 days after oral challenge and were isolated at comparable frequencies from systemic sites at 3 days, but not at 6 days, when the wild-type strain was predominant. The strains were equally invasive in intestinal epithelia with and without Peyer's patch and elicited comparable secretory and inflammatory responses and intestinal pathology in ligated ileal loops. The effect of the virulence plasmid on growth kinetics and on the outer membrane protein profile was assessed in an in vivo growth chamber. The virulence plasmid did not influence either extracellular growth or the expression of major outer membrane proteins. These observations demonstrate that the virulence plasmid is not involved in either the enteric phase of infection or the systemic dissemination of S. dublin but probably mediates the persistence of S. dublin at systemic sites.

Animals↗

Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy.

This study reports the results of cisplatin (CDDP)-based chemotherapy (CT) as sole therapy and as neoadjuvant (NA) therapy in 28 consecutive patients (pts) with advanced basal cell (BC) and squamous cell (SC) cancers of the skin. CT in 24 pts consisted of CDDP 75 mgm/m2 and doxorubicin (Dox) 50 mg/m2 intravenously (IV) every 3 weeks with Dox being omitted in four pts due to severe preexisting cardiac disease. Thirteen of the 28 pts received CT in the NA setting, five before surgery and eight before radiation therapy (RT). Response rates to CT were complete remission (CR) in eight of 28 (28%) pts, partial remission (PR) in 11 of 28 (40%) for an overall response rate of 68%. Thirteen pts received a second treatment modality with five of 13 pts having a CR to CT alone before the second modality and seven converting to CR postsecond modality for a total CR rate of 12 of 13 (92%) in the multimodality group. Duration of responses in the CT-only group ranged from 4 to 82 months; however, only two patients remain in remission in this group. Of the twelve CRs from the multimodality therapy group, 11 of 12 (91%) pts remain in CR with duration of response ranging from 3 to 81 months. Toxicities were manageable, with no toxic deaths and only five pts stopped CT secondary to side effects. This study suggests the combination of CDDP and Dox is highly effective in BC and SC cancers of the skin and by itself can produce long unmaintained remissions, but when combined with a second modality of therapy, it is capable of producing not only long unmaintained CRs but probable cures in the majority of pts.

Aged↗

Cisplatin-associated hemolytic-uremic syndrome. Successful treatment with a staphylococcal protein A column.

Cisplatin-associated hemolytic-uremic syndrome (HUS), an under-reported form of HUS induced by chemotherapy, typically pursues a fulminant and lethal course. We report the cases of two patients with squamous cell carcinoma of the head and neck who developed massive hemolysis, profound thrombocytopenia, and dialysis-dependent renal failure after therapy with cisplatin. Plasma exchange was ineffective in both patients, but plasma perfusion with a staphylococcal protein A column produced a dramatic and permanent response in the second patient. These cases show the importance of considering HUS as a cause of renal failure in such patients who receive cisplatin-based chemotherapy, and support the role of staphylococcal protein A plasma perfusion as treatment for this condition.

Aged↗

Mineral contents of brans passed through the human GI tract.

Concentrations of Cu, Fe, Zn, Ca, and phytate were measured in dry-milled corn bran, wheat brans, and soybean hulls prior to being baked in bread and after passage through the human GI tract. Significant changes in mineral concentrations in the retrieved remnants compared to the starting materials were as follows: Cu, Fe, and Zn increased by factors of from two to four and Ca increased at least ten-fold in dry milled corn bran; Ca increased and phytate decreased in wheat brans; Zn increased and Fe decreased in soy hulls. These studies show that indigestible remnants of wheat brans in the human colon associate preferentially with calcium and that dry milled corn bran remnants can be loaded with increased concentrations of all four minerals, and especially with calcium. Concentrations of minerals and phytate were significantly greater in whole fecal samples from wheat bran diets than in the corresponding retrieved bran remnants.

Adult↗

Severe central nervous system toxicity from high-dose cytarabine: expressive aphasia occurring after the second day of treatment.

A patient with acute erythroleukemia secondary to polycythemia vera was treated iv with high-dose cytarabine at a dose of 3 g/m2 every 12 hours. After the fourth dose, he developed an expressive (Broca's type) aphasia and somnolence, which progressed until after the treatment was stopped at the seventh dose. The somnolence cleared partially during the next 2 weeks but recurred after cytarabine was restarted at a dose of 100 mg/m2 daily for 7 days. The patient died 5 days later of refractory extreme thrombocytopenia and bleeding. The normal spinal fluid obtained during life and the postmortem findings were consistent with previously reported findings with central nervous system toxicity from high-dose cytarabine. Three unusual aspects of this case are early onset of symptoms, expressive aphasia as the dominant manifestation, and exacerbation of symptoms with standard doses (100 mg/m2/day).

Aphasia↗

Tuberculosis in a kiwi (Apteryx mantelli).

Generalised tuberculosis was found in a captive kiwi (Apteryx mantelli) at autopsy. Sequential faecal sampling of the other kiwis and falcons (Falco novaeseelandiae) held in the aviary revealed an excretor of Mycobacterium avium.

Journal Article↗

An extracellular fungal polysaccharide composed of 2-acetamido-2-deoxy-D-glucuronic acid residues.

The black yeast-like fungus NRRL YB-4163, now tentatively identified as Rhinocladiella elatior Mangenot, has been found to produce an extracellular microbial polysaccharide composed mainly of 2-acetamido-2-deoxy-D-glucuronic acid residues. Polysaccharide (PS) YB-4163, when isolated in good yield as the neutral potassium salt, dissolves readily in water to produce extremely viscous solutions, which form stable foams and emulsions. By depolymerizing PS YB-4163 with [14C]methanol-HCl, the polysaccharide can be both identified and quantitated radiochemically by determining the individual [14C]methyl glycosides after their separation by paper chromatography. When the methyl glycosides of PS YB-4163 were reduced with NaB3H4, only the methyl glycosides of 2-acetamido-2-deoxy-D-[6-3H]glucose were found. Analysis of the monosaccharide released from carboxyl-reduced PS YB-4163 by acid hydrolysis or methanolysis also showed 2-acetamido-2-deoxy-D-glucuronic acid to be the main constituent. Previously, the only polysaccharides known to be composed entirely or hexosaminuronic acid have been cellular products from pathogens. Of these, the antigenic polysaccharide (SPSA) from Staphylococcus aureus is composed entirely of 2-amino-2-deoxy-D-glucuronic acid, but its amino groups are substituted equally with acetyl and N-acetylalanyl groups. The specific optical rotation of PS YB-4163, [alpha]20D -75 degrees (c 0.5, water), is similar to that of SPSA (-91 degrees), and suggests beta-D-linkages that must be either (1 leads to 3) or (1 leads to 4).

Glucuronates↗

Extracellular polysaccharide from the black yeast NRRL Y-6272: improved methods for preparing a high-viscosity, pigment-free product.

When the extracellular polysaccharide from the black yeast NRRL Y-6272, composed of two parts N-acetyl-D-glucosamine and one part N-acetyl-D-glucosaminuronic acid, is isolated at maximum culture viscosity, adhering black pigment gives the polysaccharide preparations a gray-to-black appearance. Precipitation of the polysaccharide from cell-free culture supernatants with either ethanol of hexadecyltrimethylammonium bromide failed to remove the pigment. Various other methods were therefore tried for obtaining a high-viscosity polysaccharide product free of pigment. By systematically varying ingredients of defined and semidefined media, an improved medium was found that not only gave polysaccharide preparations of increased viscosity, but also increased yield. A key ingredient in this medium is L-asparagine. Also, adding autoclaved bovine serum albumin or egg albumin to this medium at the time of inoculation allowed a pigment-free polysaccharide to be isolated by standard procedures. None of several other proteins of synthetic polyamides tested were as effective as bovine serum albumin or egg albumin. In an alternate approach, pink mutants obtained by irradiation of the parent black strain with ultraviolet light, apparently produce the same extracellular polysaccharide free of any pigment but in lower yields or inferior in quality.

Acetylglucosamine↗