Simultaneous primary closure of four fasciotomy wounds in a single setting using the Sure-Closure device.
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Biomedical subjects
Publications and source records attributed to L M Jones.
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Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3 alpha and 3 beta addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.
A major route for the spread of ovarian cancer is by the attachment of tumour cells to the mesothelium lining in the peritoneal cavity. The expression of various adhesion molecules has been measured on freshly-prepared mesothelial cells, two mesothelial cells lines and 13 established ovarian tumour cell lines. The integrins beta 1 and beta 3, ICAM-1, and CD44 were detected on all mesothelial preparations and on many or all of the tumour lines. VCAM-I was expressed exclusively on the mesothelial cells and Lewis x was expressed on half of the tumour lines. There was low or no expression of sialyl Le(x), sialyl Le(a), integrins alpha 4, beta 1, beta 4, or E and P selectins. Only CD44 expression was significantly affected by trypsin treatment. From the known interactions of adhesion molecules, the results suggest that CD44, and beta 1 and beta 3 integrins may be important in tumour/mesothelial interactions.
The adhesion to mesothelial monolayers of eight cultured ovarian tumour cell lines was studied in multiwell plates as a model for some of the interactions of ovarian cancer in the peritoneal cavity. When only the upper half of the conditioned medium (CM) from a confluent mesothelial cell culture was aspirated, the adhesion of the tumour cells was low (3.5%-36%). When the medium was removed completely the adhesion increased. The tumour cell lines showing the greatest enhancement of adhesion were those which had previously been shown to express the highest amounts of CD44. By adding erythrocyte suspensions to mesothelial cells it was shown that there was a pericellular coat around the mesothelial cells that could be destroyed by aspirating the medium, or by treating the medium with hyaluronidase (Hase). Treatment of the CM with Hase also considerably increased tumour cell adhesion. Furthermore, CM was shown to contain high amounts of hyaluronic acid (HA). HA blocked adhesion in the absence of CM, but the effect was not as large as that produced by the pericellular coat. It is proposed that pericellular HA produced by mesothelial cells has an important role in the invasion of ovarian tumour cells in the peritoneal cavity.
Infrequently reported, serious allergic reactions to topical antimicrobial agents used in the treatment of burn injuries are a potential source of confusion. To avoid misdirected therapy, an understanding of the manifestations of such reactions is important. Two recent cases of serious allergic reactions, one to silver sulphadiazine, one to mafenide acetate, are presented and the literature is reviewed.
Functional interactions between the enantiomers of the dihydropyridine 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyridi ne carboxylic acid methyl ester (Bay K 8644) and the benzoylpyrrole methyl 2,5-dimethyl-4-[2(phenylmethyl)benzoyl]-H-pyrrole-3-carboxylate (FPL 64176) were investigated on L-type Ca++ channels in guinea pig ileal longitudinal smooth muscle. The effects of these drugs, when applied individually, were as described in earlier studies. For instance, both (-)-(S)-Bay K 8644 and FPL 64176 caused concentration-dependent contraction, which is consistent with Ca++ channel activation, whereas (+)-(R)-Bay K 8644 gave concentration-dependent relaxation, which is consistent with Ca++ channel inhibition. The activities of the different drugs were dependent on the extracellular levels of KCI. When applied in combination, however, the responses evoked were not those predicted from the effects of the drugs applied individually. Contractions produced by FPL 64176 (25 nM to 1 microM) were abolished in the presence of 100 nM (-)-(S)-Bay K 8644 but were potentiated by 10 to 150 nM (+)-(R)-Bay K 8644 and inhibited by 1 microM (+)-(R)-Bay K 8644. Conversely, contractile responses to (-)-(S)-Bay K 8644 were abolished by 100 nM FPL 64176. In the presence of 1 microM FPL 64176, however, (-)-(S)-Bay K 8644 gave concentration-dependent relaxation of the muscle, which is consistent with Ca++ channel inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Ovarian cancer is the second most common gynaecological cancer in the UK, causing 2000 deaths per year. It spreads by shedding cells which attach to the mesothelial lining of the peritoneal cavity. In order to quantitatively study this interaction, a model system was developed in which mesothelial cells were cultured as monolayers in multiwell plates, and ovarian tumour cells were added that had been pre-labelled with a fluorescent dye (calcein). Synchronous interaction between the two populations was achieved by brief centrifugation at low g and the degree of attachment was measured on an automated fluorimeter after washing away the unbound cells. Using this procedure it was possible to measure tumour cell adhesion in 96 wells in 3-4 h. The reproducibility of the method was high even after short incubation times and the background absorbance was so low that the adhesion of less than a 1000 cells could be easily detected. The method works equally well for all ovarian tumour cell lines so far studied, and in preliminary experiments, it was shown that it can be used to screen for the effects of various blocking agents.
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Nonoperative management of blunt hepatic injury (BHI) has become more widely accepted. A prospective trial was undertaken to test the belief that clinical state could identify the patients with BHI confirmed by computed tomography (CT) who could be safely managed without a surgical operation. Patients were excluded from nonoperative management only if they manifested hemodynamic instability, the presence or suspicion of any other injury requiring laparotomy, or would be unavailable for controlled monitoring. Of 60 patients treated for BHI, 30 were managed nonoperatively. The 30 who had laparotomies served as a comparative group. The groups were statistically similar in age, sex, and Injury Severity Score (ISS). The group managed nonoperatively had significantly more severe BHI. There were no deaths or delayed laparotomies in the nonoperative management group. The groups had similar ICU and total hospital stays when analyzed as independent variables or with control for BHI grade and ISS. Transfusion requirements were significantly lower for the nonoperative management group when analyzed independently or when controlled for BHI grade, ISS, and the number of non-abdominal injuries. Nineteen (63%) patients managed nonoperatively were followed until their CT scans showed complete resolution. None had complications. We conclude that nonoperative management of BHI is a safe and effective technique applicable to hemodynamically stable patients who lack other indications for laparotomy and who can be adequately monitored.
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In a group of 880 patients undergoing inguinal herniorrhaphy using local anesthesia, the incidence of postoperative urinary retention was 0.2 per cent. During the same period, a similar group of 200 patients had their hernias repaired using general or spinal anesthesia. The incidence of postoperative urinary retention was 13 per cent. The authors contend that the use of local anesthesia in inguinal hernia repair almost eliminates postoperative urinary retention.
The inhibition of DNA synthesis in triciribine (TCN)-treated L1210 cells was shown to involve two mechanisms, with different concentration dependence. (a) Initiation of new replicons and possibly of Okazaki fragments was inhibited when the cells were treated with 0.1 microM TCN. The inhibition of replicon initiation was shown by the rate of alkaline elution of [3H]DNA from 15-min-[3H]thymidine-labeled cells being slower if the cells had been pretreated with TCN, indicating that the average size of actively replicating DNA strands was increased. (b) At 1 microM TCN elongation of previously initiated DNA chains was also inhibited. This conclusion was suggested by the decrease in the rate of alkaline elution of [3H]DNA, during postlabeling incubation, being less if TCN was included in the medium. The mechanism of inhibition of DNA synthesis by TCN was shown not to involve DNA strand breakage or cross-linking, inhibition of polyamine biosynthesis, inhibition of purine de novo biosynthesis, inhibition of DNA polymerase alpha or DNA primase, or inhibition of ligation of Okazaki fragments. The effects of TCN on the incorporation of [3H]thymidine into Okazaki fragments and higher molecular weight DNA suggested the possibilities of inhibition of Okazaki fragment initiation and/or DNA polymerase delta.
It has been suggested that defects in the relationship between ribonuclease and its proteinaceous inhibitor could be a contributory factor in Alzheimer's disease. We have investigated this possibility further by analysing free and bound enzyme activities and the activity of the inhibitor in nine regions of diseased and normal brain. These were chosen to include areas known to be affected by the disease, regions not histologically affected but thought to be involved in the disease process, and areas not thought to be involved in the disease. Neither the enzyme nor its inhibitor is defective in its activities in the chosen areas of Alzheimer's disease brain when compared with those of carefully age-matched controls.
Comparing 14 women with and 55 women without endometriosis, the authors found no significant differences in the prevalence of affective disorder. They discuss the discrepancy between their finding and Lewis et al.'s finding of an association between affective disorder and endometriosis.
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1. N tau-methylhistidine excretion, growth rate, food consumption and body composition was determined in 12 4 to 5 week old chickens sampled from each of 4 lines selected for increased body-weight gain (line W), for increased food consumption (line F), for improved efficiency of food utilisation (line E) or at random (line C), after 12 generations of selection. 2. The use of N tau-methylhistidine as an index of myofibrillar protein breakdown was validated in male and female chickens of lines E and F by following the fate of injected N tau-(14CH3)methylhistidine. Most of the radioactivity (79.3 +/- 1.1%) was excreted in 4 d, with the remainder retained in the carcase. In excreta, 94 +/- 2% of the radioactivity was associated with free N tau-methylhistidine and for the carcase, this value was 88 +/- 3%. 3. In the main experiment, final body weights averaged 497, 651, 588 and 537 g and food: gain ratio averaged 2.47, 2.21, 3.14 and 2.06 for lines C, W, F and E respectively, Carcase protein content (g/100 g body weight) was not different between the lines. 4. N tau-methylhistidine excretion was 5.86, 5.48, 6.43 and 4.99 mumoles/mole carcase-N/d for lines C, W, F and E, respectively. The rate for line F was significantly higher than for lines W and C and that for line E was significantly less than for the control line. 5. The N tau-methylhistidine excretion rate was positively correlated with food: gain ratio. 6. Selection for rapid growth, high food consumption or improved food utilisation results in changes in N tau-methylhistidine excretion which suggest proportionate changes in muscle protein turnover.
Third- and fourth-degree burns, which extend beyond the layers of the skin, are the most severe and difficult to rehabilitate. In this case report, a patient's recovery from exposed Achilles tendons bilaterally secondary to a severe burn injury is described. The Dynasplint, a spring-loaded orthosis designed to deliver a low-load, prolonged stretch to healing connective tissue, was used to facilitate the patient's recovery from an initial loss of -29 and -27 degrees of dorsiflexion of the right and left ankles, respectively. The patient's progress is reported from bed rest to independent ambulation at the time of discharge from the hospital.