Biomedical subjects
Publications and source records attributed to D G Smith.
Some of the ammonia produced by hydrolysis of urea by Ureaplasma urealyticum is channelled into an anabolic pathway with resultant 'de novo' synthesis of citrulline. The organism appears to possess ornithine carbamoyltransferase and carbamoyl phosphate synthetase or some modified form of these enzymes.
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This study examined whether an ambient odor can act as a contextual cue for retrieval of verbal stimuli. Subjects (N = 47) learned a list of 24 words while exposed to one of two odors (either jasmine incense or Lauren perfume) and subsequently relearned the list with either the same or the alternative odor present. Superior memory for the word list was found when the odor present during the relearning session was the same one that had been present at the time of initial learning, thereby demonstrating context-dependent memory. There were no differences in initial learning between the two odor conditions. No differences in pleasantness or intensity were found between the odors.
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The challenges presented by managed care arrangements and third-party utilization controls have led hospitals to strengthen internal utilization management programs. This article reports findings from a set of case studies on how hospitals have adapted their utilization management programs to their environments. While knowledge acquired from case studies should not be overgeneralized, the findings of these studies suggest some lessons that merit consideration by hospitals advancing their own programs in utilization management.
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Twelve patients who had a large ulceration over the heel were managed with a partial calcanectomy, in lieu of a below-the-knee amputation, after unsuccessful non-operative treatment of the ulcer. Only patients who had an ankle-arm index (the ratio of blood pressure at the ankle to the brachial blood pressure) of more than 0.45, a transcutaneous PO2 of more than twenty-eight millimeters of mercury (3.7 kilopascals), a level of albumin of more than 3.0 grams per deciliter (thirty grams per liter), and a total lymphocyte count of more than 1500 were managed with a partial calcanectomy. The primary diagnosis was diabetes in seven patients, peripheral vascular disease in three, quadriplegia in one, and myelodysplasia in one. The duration of follow-up averaged thirty-three months and ranged from seven to sixty-four months. The wound healed after the partial calcanectomy in ten of the twelve patients. Nine of these ten patients maintained the level of mobility that they had had preoperatively. (One patient was unable to walk because he was quadriplegic before the operation). The wound did not heal in two patients, and those patients ultimately had a below-the-knee amputation and a decrease of one grade on the scale that was used to evaluate walking ability.
Danofloxacin, a novel fluoroquinolone antimicrobial drug was evaluated in the treatment of acute bacterial pneumonia in recently housed beef cattle of approximately 300 kg liveweight. The clinical responses of 67 pneumonic cattle treated with danofloxacin were compared with those of 65 cattle treated with oxytetracycline, both treatments being given by intramuscular injection for either three or five days, depending on clinical response. Both treatments resulted in a rapid fall in group mean rectal temperature and improved the clinical condition of the majority of cases. However, in comparison with oxytetracycline, danofloxacin therapy was characterised by significantly fewer treatment days, a higher response rate, significantly better reduction of pyrexia and fewer cattle requiring re-treatment.
A plasmid expression vector (pZWtac1) was constructed which allowed inducible overexpression of the uracil-DNA glycosylase (Ung) inhibitor (Ugi)-encoding gene (ugi) in Escherichia coli. In this plasmid, the ugi gene was under the control of both its own promoter and the tac promoter. Constitutive expression of the ugi was observed in the absence of isopropyl-beta-D-thiogalactopyranoside (IPTG). In the presence of 1 mM IPTG, the Ugi protein was overproduced to an approx. 16-fold higher level, and accounted for approx. 19% of the total soluble cellular proteins. Following high-level production in E. coli, the Ugi protein was purified to apparent homogeneity. Using E. coli Ung, we observed that Ugi inactivated the enzyme in a noncompetitive manner. Kinetic studies revealed a Ki value (0.14 microM) of approx. twelve-fold lower than Km value (1.7 microM) of glycosylase. Ugi did not act synergistically with free uracil to inhibit E. coli Ung suggesting that uracil and Ugi could share a similar mode of inhibition.
The merger of rural primary care and home health services offers the potential of increasing the administrative efficiency of health care, and thereby enhancing quality of care and increasing access to services, particularly health promotion. In a merger of rural health services in Northeastern Vermont, a survey of key community leaders revealed that improved organization of services, improved health status and greater accessibility of services were benefits expected and to some extent realized as a result of the merger process. The desire to preserve community-based services and having a common philosophy were important factors which served to initiate the merger. The actions of a few key individuals and the support of involved organizations were instrumental in continuing the process.
A retrospective 3-year survey of 311 patients sustaining 564 facial fractures in a medium-sized metropolitan area is presented. Etiology, distribution and treatment of these facial fractures are reported and compared with earlier studies, where changing patterns of etiology and treatment were noted. Contemporary knowledge of facial injuries is important if diagnosis and treatment are to be accurate and treatment optimal.
The synthesis of a novel series of smooth muscle relaxants which have been shown to act via the opening or activation of potassium channels is described. Compounds have been evaluated for their ability to inhibit spontaneous tone in guinea pig isolated trachealis and structure-activity relationships are discussed. One compound in particular, 1,1-dimethyl-5-nitro-3-(2-pyridon-1-yl)indan-2-ol, (16) was identified as a potent relaxant of airways smooth muscle in vitro with IC50 = 0.15 microM and was found to significantly inhibit histamine-induced dyspnoea in conscious guinea pigs when given orally 30-45 min prior to challenge.
Structural modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions. Analogues in which the hydroxyl group at C-3 has been oxidized or removed are also disclosed. Such analogues display an interesting profile of smooth muscle relaxant activity in the guinea pig isolated trachea, not all of which appears to result from the opening of potassium channels, but few compounds retain useful in vivo activity. However, one compound in particular, 6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide (13) was shown to be a potent potassium channel activator in vitro and to provide prolonged protection to guinea pigs from the respiratory effects of inhaled histamine.
Fifty coagulase-negative staphylococci (CNS) strains were investigated for adherence to both silicone rubber and polystyrene using a microtitre tray system. Culture in an atmosphere containing a physiological level of carbon dioxide (5% CO2) profoundly affected adherent growth to both surfaces. Most strains adhered less well in this atmosphere compared to in air alone, with mean reductions in adherence of 84% and 86% to silicone rubber and polystyrene respectively. Occasional strains adhered better in 5% CO2. The effects of antibiotic concentrations equivalent to 1/4 MIC of cefuroxime, ciprofloxacin, vancomycin and teicoplanin on the adherence of 10 CNS strains were also studied. Vancomycin and teicoplanin frequently increased adherence to silicone rubber and polystyrene compared to controls. The effects of antibiotics on adherence were not only strain dependent but also sometimes atmosphere or surface specific. Antibiotic-induced changes in adherence did not appear to correlate with changes in strain protein profiles or surface hydrophobicities.
Strains of coagulase-negative staphylococci (CNS), including Staphylococcus epidermidis, S. hominis, S. warnerii, S. simulans, S. capitis, S. haemolyticus and S. saprophyticus, were isolated from patients with continuous-ambulatory-peritoneal-dialysis-related peritonitis. The cell wall and cytoplasmic membrane protein profiles of CNS strains cultured in either nutrient broth (NB) or pooled human peritoneal dialysate (HPD) were compared. Some interspecies variation in both the wall and membrane protein profiles was noted. However, the cell wall protein profiles of HPD-grown CNS strains differed markedly from those cultured in NB. Growth in HPD resulted in a marked reduction in the total number of cell-wall-associated proteins but up to three antigenically related proteins in the 40-56 kDa range, depending on the species, predominated. Growth in HPD also resulted in the induction of two iron-repressible cytoplasmic membrane proteins (IRMPs) of 32 and 36 kDa in S. epidermidis. Other CNS strains only appeared to express a single IRMP, which varied in molecular mass from 32 to 36 kDa. Whilst the IRMP in these CNS strains showed considerable antigenic homology with the 32 kDa IRMP, the S. warneri IRMP showed cross-reactivity with both the 32 and 36 kDa IRMPs of S. epidermidis. Immunoblotting experiments revealed that whilst the CNS cell wall proteins were poorly immunogenic, the IRMPs were the immunodominant CNS protein antigens, reacting strongly with antibodies present in HPD. This finding provides evidence to suggest that the IRMPs are expressed in vivo during infection.
A study of the conjugal transfer of ColV,I-K94 tn 10 from acid-treated donors suggested that acid-habituated recipients repair acid-damaged plasmid DNA better than those that are not habituated. The presence of an increased repair activity for acid-damaged DNA in habituated cells was confirmed by isolating pBR322 from acid-treated organisms; habituated cells produced more transformants when transformed by it than did non-habituated ones. Additionally, agarose gel electrophoretic studies of pBR322 DNA isolated from acid-damaged cells and tests of its transforming activity both indicated that plasmid DNA in habituated cells is less damaged by extreme acidity than is that in non-habituated organisms.
Induction of acid resistance (habituation) in Escherichia coli at pH 5.0 took ca 5 min in broth at 37 degrees C and 30-60 min in minimal medium. Induction occurred at a range of pH values from 4.0 to 6.0; it was dependent on continuing protein and RNA synthesis but substantial acid resistance appeared in the presence of nalidixic acid. Acid resistance was long-lasting; organisms grown at pH 5.0 retained most of their resistance after 2 h growth at pH 7.0. Organisms grown at pH 5.0 showed increased synthesis of a number of cytoplasmic proteins compared with the level in cells grown at pH 7.0. DNA repair-deficient strains carrying recA, uvrA or polA1 mutations were more acid-sensitive than the repair-proficient parents but were able to habituate at pH 5.0. Organisms grown at pH 5.0 transferred the ColV plasmid much more effectively at acid pH than did those grown at pH 7.0 and habituated recipients appeared better able to repair incoming acid-damaged plasmid DNA than did those that were non-habituated. Induction of acid resistance at pH 5.0 may be significant for the survival of organisms exposed to periodic discharges of acid effluent in the aquatic environment and habituation may also allow plasmid transfer and repair of acid-damaged plasmid DNA during or after such exposure.
The efficacy of plaque control as a means of preventing cyclosporin-induced gingival overgrowth was assessed in 27 adult renal transplant patients. After baseline examination, patients were randomly allocated to receive intensive oral hygiene instructions, scaling and root planing (OH group) or no treatment (no treatment group). Gingival condition was assessed 6 months after baseline and changes in gingival form were related to various periodontal and pharmacokinetic measures. In both treatment groups, there was a significant increase (P less than 0.05) in gingival hyperplasia scores at 6 months. In the OH group, plaque scores were significantly lower (P less than 0.05) at 6 months, whereas in the no treatment group, a significant increase in plaque scores, gingival inflammation and probing depths was observed at 6 months. Dosages of cyclosporin, whole blood concentrations of cyclosporin, baseline gingival index, hyperplasia scores, and 6-month plaque index were not important determinants for the increase in gingival over-growth in both treatment groups. It is concluded that attention to plaque control and the removal of local irritants is of some benefit for the gingival health of cyclosporin-treated adult renal transplant patients, but these measures alone did not prevent gingival overgrowth. Pharmacokinetic variables of cyclosporin and various periodontal measures were not good predictors of cyclosporin-induced gingival changes.