Biomedical subjects
Publications and source records attributed to S Hill.
Methylene blue was placed in the pharynx of 64 patients undergoing anaesthesia with the laryngeal mask. No leak of dye into the larynx was detected on fibreoptic inspection of the inside of the mask in any subject. The use of the laryngeal mask as a means of protecting the airway during procedures such as minor nasal operations is therefore supported.
The intensity of the cutaneous response was assessed after application of a standard irritant to increasing areas of normal forearm skin. Twenty subjects were tested to determine the minimal irritant dose (MID) to dilutions of aqueous sodium dodecyl sulphate. Each subject was then treated under occlusion for a period of 24 h with different areas of filter paper (9, 25, 100, 225 and 400 mm2) soaked with the concentration required to give the individual's MID. At 25 and 48 h the degree of erythema was assessed using a 0-4 arbitrary scale, a 10-cm visual analogue scale (VAS) and an erythema meter. Cutaneous blood flow was measured with a laser-Doppler device and cutaneous oedema measured by pulsed A-scan ultrasound. The results at 25 and 48 h were almost identical. Both forms of visual assessment (arbitrary scale and VAS) showed an increase in perceived erythema with increasing area and this was confirmed by the erythema meter. Further area-related changes were noted with both cutaneous blood flow and ultrasound measurements.
The authors further describe investigations of a family originally reported by Bundey & Smyth in 1974 with a diagnosis of the Smith-Lemli-Opitz syndrome. Chromosome studies performed for the fourth time revealed that the mother had a presumptive t(4;22) translocation. The importance of reviewing earlier diagnoses, including repeating the chromosome studies if indicated, in order to arrive at a more accurate diagnosis is stressed. It is also important to provide the cytogenetics laboratory with clues to any possible clinically-recognisable chromosome syndrome, and to be prepared to examine the chromosomes of the parents of the affected case, even if the patient's karyotype appears normal. In this particular family, the correct diagnosis in the affected girls led to a realization that their brother had a 50% risk of producing unbalanced offspring.
Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.
Precocious puberty often leads to short adult height. Since the introduction of luteinizing hormone-releasing hormone (LHRH) agonist treatment for LHRH-dependent precocious hormone (LHRH) agonist treatment for LHRH-dependent precocious puberty in 1979, several reports have shown increased predicted height among LHRH agonist-treated children. To determine whether the LHRH agonist deslorelin can normalize the adult height of children with precocious puberty, we are conducting a long-term pilot study involving 161 children. This report describes the first 44 children to have attained final or proximate adult height. These children were 7.1 +/- 1.2 (mean +/- SD) yr old (bone age 11.8 +/- 1.5 yr) and had been in puberty for 3.1 +/- 0.3 yr at the start of treatment. They were treated with deslorelin (4 micrograms/kg/day sc) for 4.1 +/- 1.3 yr and had been withdrawn from treatment for an average of 2.4 yr at the time of this study (age 13.6 +/- 0.9 yr). Fourteen of the 44 children, who had grown less than 0.5 cm during the previous year, were considered to have attained adult height. The other 30 children had achieved 98.6% of predicted mature height (Bayley-Pinneau method) and were considered to be at proximate adult height. The final or proximate adult height of these 44 children averaged -1.1 SD compared to the adult height of the normal population. This height was significantly greater than the pretreatment height (-1.1 vs. -2.0 SD, P less than 0.01), but significantly less than both the predicted height at the end of treatment (-1.1 vs. -0.5 SD, P less than 0.01) and the target height derived from the mean height of the parents adjusted for the sex of the child (-1.1 vs. 0.1 SD, P less than 0.01). The observation that the Bayley-Pinneau height prediction at the end of treatment overestimated the actual adult height emphasizes the importance of using final height data to assess the ultimate impact of LHRH agonist treatment. It also indicates the need for caution when predicting the adult height of children who are still receiving treatment. We conclude that deslorelin has improved the adult height of these patients but has not fully restored height to the patients' genetic potential. We hypothesize that further improvement will be seen in patients who are treated with less delay and at a younger bone age.
Genetic complementation of an Escherichia coli double mutant was used to isolate and express the gene coding for Plasmodium falciparum glucose phosphate isomerase. The gene contains a 1773-base pair open reading frame, has no introns, and maps to P. falciparum chromosome 14. 34% of the deduced amino acid sequence is identical to human glucose phosphate isomerase, with highest similarity in regions of the proposed active sites. The putative initiation site of translation was determined by deletional and oligonucleotide mediated, site-specific mutageneses. Our data suggest that key metabolic enzymes of Plasmodia can be cloned and expressed in E. coli without prior knowledge of the primary amino acid or nucleic acid structure.
Recombination-dependent alterations of their expressed pilin gene (pilE) enable gonococci to synthesize a myriad of structurally/antigenically different pili and to reversibly switch their pilus production on and off. These changes have been ascribed both to DNA transformation and to intragenomic recombination between pilE and silent pilin genes (pilS). We examined the pilus changes in gonococci that are incompetent for transformation because of their DNA uptake deficiency (dud) mutation, pilus- (P-) phenotype, or both. Though incompetent for DNA transformation, dud cells displayed pilus antigenic variation and underwent reversible pilus variations much like their wild-type parent. Wild-type P- with a pilE nonsense mutation were also virtually nontransformable, but they reverted to P+ at high frequencies. The pilin mRNA sequence changes that accompanied pilus transitions in these nontransformable dud and P- gonococci represent insertion of pilS stretches into their respective pilE, apparently via intragenomic recombination.
Explore the source record for details and available documents.
In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 micrograms/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0-30 hr was significantly higher for the patch containing 5% IPM.
Klebsiella pneumoniae synthesized only b-type and d-type cytochromes under the wide range of growth conditions tested, and reaction with CO revealed two potential oxidases. The o-type oxidase was produced only in the presence of O2 and appeared to be repressed by glucose. The d-type oxidase was, by contrast, produced only in the absence of measurable O2 (less than 1 microM), and was the only oxidase expressed in nitrogen-fixing conditions. It was extracted from the membrane, purified and shown to be similar to that from E. coli in being a heterodimer (subunits of Mr 52,000 and 35,000), in containing two distinguishable b haems and haem d (one or two molecules per molecule of oxidase), and in being able to react with O2 to give a stable oxygenated intermediate. The purified d-type cytochrome oxidase had a very high affinity for O2 (Km 20 nM; measured by the spectral properties of leghaemoglobin). It is proposed that this provides a role for this oxidase in lowering the O2 concentration to allow nitrogenase synthesis and function, and to provide a terminal oxidase to permit electron-transport-coupled ATP synthesis which supports the increase in efficiency of nitrogen fixation observed under microaerobic conditions.
Two studies were designed to assess the effect of abrasive preparations on the skin and to test the specificity of the effect of topical tretinoin in the management of chronic photodamage to the skin. In the first study two abrasive preparations (Brasivol fine and Brasivol medium) were compared with white soft paraffin and no treatment in eight volunteer subjects for their effects on the epidermis. The study was conducted over 3 days and measurements were taken of the effects on dansyl chloride-induced fluorescence to assess desquamation, epidermal thickness, and the tritiated thymidine autoradiographic labelling index. The abrasives were found to increase the desquamation rate significantly and to increase epidermal thickness and the epidermal labelling index compared to white soft paraffin and no treatment. In the second study the effect of one of the abrasive preparations (Brasivol medium) was compared with 0.05% tretinoin cream (Retin A) on the photodamaged skin of the dorsal aspects of the forearms of 12 subjects over an 8-week period. Cutaneous blood flow measured by the laser-Doppler flowmeter was found to be significantly increased in the abrasive-treated sites, but there was only a non-significant trend to increased blood flow in the tretinoin-treated sites. Measurements of skin thickness using pulsed A-scan ultrasound demonstrated that both treatments produced significant increases in thickness over the 8-week period but the increase was greater for the abrasive treated site. Measurements of the skin extensibility at the treated sites were made using a uniaxial extensometer. Forces needed for 30% skin extension were increased in the abrasive-treated sites only. Measurements of epidermal thickness and of [3H]-thymidine autoradiographic labelling indices showed greater increases in the abrasive-treated sites than in tretinoin-treated sites compared to untreated sites, but these increases were not statistically significant. No significant inflammation and no changes in the degree of elastosis or the presence of a 'repair zone' were found in any of the post-treatment biopsies. The results indicate that some of the changes produced in the skin by topical tretinoin that are taken to indicate a specific antiphotoageing effect may not in fact be specific and can be achieved by an abrasive preparation.
Escherichia coli strains that lacked the d-type cytochrome oxidase, the terminal oxidase with a high affinity for O2, grew anaerobically as well as the wild type did and were not impaired in the ability to evolve H2 from either glucose or formate. The anaerobic synthesis and activity of nitrogenase in transconjugants of these strains carrying Klebsiella pneumoniae nif genes were also normal. However, the behavior towards O2 of anaerobically grown bacteria lacking the d-type oxidase differed from that of the wild type in the following ways: the potential O2 uptake was lower, H2 evolution and nitrogenase activity supported by fermentation were more strongly inhibited by O2, and microaerobic O2-dependent nitrogenase activity in the absence of a fermentable carbon source did not occur. These results show that the d-type oxidase serves two functions in enteric bacteria--to conserve energy under microaerobic conditions and to protect anaerobic processes from inhibition by O2.
Several in vitro studies suggest the involvement of active oxygen metabolites in cell damage caused by asbestos. To determine if lung injury, inflammation, and asbestosis could be inhibited in vivo in a rapid-onset, inhalation model of disease, a novel method of chronic administration of antioxidant enzymes was developed. In brief, Fischer 344 rats were treated with polyethylene glycol-conjugated (PEG-) superoxide dismutase or catalase in osmotic pumps over a 10-day (5 days/wk for 2 wk) or 20-day (5 days/wk for 2 wk) period of exposure to crocidolite asbestos. Control rats included sham-exposed animals and those exposed to asbestos but receiving chemically inactivated enzymes. After 10 days of exposure to asbestos, lactic dehydrogenase (LDH), alkaline phosphatase, and total protein in bronchoalveolar lavage (BAL) were measured in one group of rats. Total and differnetial cell counts in BAL also were assessed. After 20 days of exposure, lungs of an additional group of rats were evaluated by histopathology and by measurement of hydroxyproline. Asbestos-associated elevations in LDH, protein, and total cell numbers in BAL were reduced in rats receiving PEG-catalase. Decreases in numbers of alveolar macrophages, polymorphonuclear leukocytes, and lymphocytes occurred in these animals. Exposure to asbestos for 20 days caused significant increases in both the amount of hydroxyproline in lung and the severity and extent of fibrotic lesions as determined by histopathology. These indicators of asbestosis were inhibited in a dosage-dependent fashion in rats receiving PEG-catalase. Use of inactivated PEG-catalase failed to boost serum levels of catalase and did not inhibit asbestos-induced elevation of hydroxyproline in lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The frequency and antigen-bearing characteristics of dendritic cells (DC) within draining lymph nodes have been examined during antigenic competition in contact sensitivity. Pre-exposure of mice to oxazolone on the flank resulted in a marked depression of subsequent fluorescein isothiocyanate (FITC)-induced lymph node cell (LNC) proliferation. Antigenic competition was associated with an increased frequency of DC in the draining lymph nodes, but also with a reduced amount of antigen per cell. Thus, at 24 hr the draining nodes of FITC-challenged mice previously exposed to oxazolone exhibited an increased number of DC compared with control animals. Flow cytometric analysis revealed, however, that the percentage of antigen-bearing DC was reduced and that the median amount of antigen borne by DC was lower. Since exposure to oxazolone caused a significant increase in the frequency of DC in distant nodes, the changes observed in antigenic competition may, at least in part, be attributable to systemic effects on DC migration following application of the first antigen. These data indicate that the reduced primary proliferative response which characterizes antigenic competition in contact sensitivity is associated with, and may result from, induced changes in dendritic cell behaviour.
Twenty-four hours after skin painting mice on the flank with the contact sensitizer fluorescein isothiocyanate (FITC), the number of dendritic cells (DC) increased sharply, not only in draining but also in contralateral (CLN) and distant lymph nodes. High levels of antigen were detected on up to 50% of DC isolated from draining lymph nodes (DLN), and these cells were potent stimulators of naive T cells in vitro. Less than 3% of DC from contralateral and distant lymph nodes carried detectable antigen and did not induce significant T-cell proliferation. A significant number of DC had migrated to draining, contralateral and distant lymph nodes without acquiring detectable antigen. This indicates that there is a systemic signal causing the movement of DC to lymph nodes. This appears to be independent of mature T cells, as the systemic migration of DC also occurred in nude mice.
The response of different stages of spermatogenesis to heat have been assessed by scoring the cell types in testis tubules at 14, 28 and 35 days after treatment. Deficiencies in spermatids at these times can be related back to the stage that the precursor would have been in 14 and 28 days earlier. On the 35th day the number of repopulated tubules was counted. The testes of CBA mice were heated using a radiofrequency equipment and controlled by a thermocouple in the other testis. Great difficulty was experienced in achieving a uniform temperature of 43 degrees C for a period of 30 minutes. The testes can be grouped into 2 categories: those with an appropriate heat profile and those which were overheated. The data showed that the weight of the testis at 14 days was only 65% of control and had slightly increased by 28 days to 88%. The number of sperm heads and late spermatids decreased to 33% at 14 days, but had increased to 88% by day 28. On the 35th day after heating to 43 degrees C cell depletion and shrinking of the tubules occurred. Sixty-four percent of examined tubules only had normal appearance and were repopulated. This shows that the temperature of 43 degrees C impairs the stem cells and it can be a warning to clinicians who think of applying hyperthermia for treatment of human tumors located in the testis area.
Between April and November, 1985, a study of the levels of organotins in adult and seed Crassostrea gigas grown in the southwest and southeast of England was carried out. This work corresponds with a similar study of organotin water levels (reported separately). The analytical procedure used was directly coupled high performance liquid chromatography-flame atomic absorption spectrometry. Individual adult oysters and groups of 20-40 seed oysters were taken for analysis on a monthly basis. The profiles of tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) are discussed in relation to each other and levels found in the waters. In general, levels of all three organotin species were found to be higher in the seed oysters. Mean levels of TBT reached 3.1 micrograms g-1 in seed oysters from the Exe, Devon, in October, whereas mean levels of DBT and MBT reached 16.1 and 16.7 micrograms g-1 in Teign, Devon, seed oysters in October. Bioconcentration factors of approximately 1000 were found, but seem to be greater when lower levels of TBT were present in the water, perhaps indicating a more 'efficient' removal from the water. The degree of shell thickening was calculated for all oysters submitted for analysis. The highest percentage of adult oysters with severely thickened shells was found at Tollesbury Fleet, where 61% of oysters showed shell thickness index values of six or less. Generally, two peaks in TBT levels in the oysters were observed, in the late spring and early summer: these seem to correlate with peak levels of TBT in the waters immediately preceding these times. A large proportion of the DBT and MBT found in the oysters seems to come from the metabolism of the TBT ingested. It is suggested that high sediment loadings may contribute to the severe deformation of oysters grown at Tollesbury Fleet, but only in the presence of TBT.