Biomedical subjects
Publications and source records attributed to C J Lloyd.
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We describe a 36-year-old patient with a stage III carcinoma (pT2N1M0) of the tongue that presented in the second trimester of pregnancy. It was treated by primary excision and reconstruction with a free flap. To our knowledge this is the first reported case of successful microvascular free tissue transfer for oral cancer during pregnancy.
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This study assessed the clinical outcome after insertion of a percutaneous endoscopic gastrostomy tube (PEGT) by a maxillofacial team in a series of 54 patients. The indication for PEG feeding was any patient with oropharyngeal cancer who was unlikely to return to oral feeding within 14 days. Fifty-two patients (96%) had tubes successfully inserted at the time of examination under anaesthesia (n = 19) or definitive operation (n = 33). Feeding was established at a median of 2 days (range 1-6). Median duration of tube feeding was 18 weeks (range 4-70). There were no deaths or major complications and 10 minor complications. No tube was lost or required premature removal. We conclude that insertion of a PEG tube is a procedure that can be done safely by maxillofacial surgeons.
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The study assessed the dosage, clinical sedative effect, and safety of intranasal midazolam in 32 children. Data were complete for 29 patients (21 with lacerations and 8 cases of dental trauma). Sedation was adequate to ensure successful completion of treatment under local with or without topical anaesthetic in 22 of the 29 cases (76%). They became sedated at a mean (SD) of 14 (5) minutes, with completion of treatment at 20 (13) minutes. Sedation was achieved with a mean (SD) of 5 (2)mg of midazolam. There were no signs of respiratory depression or of oxygen desaturation below 94% on pulse oximetry. No supplemental oxygen was required and there were no other complications. We conclude that intranasal midazolam is a safe and effective alternative to general anaesthesia in the definitive treatment of children with oral and maxillofacial injuries.
The performance of a diagnostic test is summarized by its receiver operating characteristic (ROC) curve. Under quite natural assumptions about the latent variable underlying the test, the ROC curve is convex. Empirical data on a test's performance often comes in the form of observed true positive and false positive relative frequencies under varying conditions. This paper describes a family of regression models for analyzing such data. The underlying ROC curves are specified by a quality parameter delta and a shape parameter mu and are guaranteed to be convex provided delta > 1. Both the position along the ROC curve and the quality parameter delta are modeled linearly with covariates at the level of the individual. The shape parameter mu enters the model through the link functions log(p mu) - log(1 - p mu) of a binomial regression and is estimated either by search or from an appropriate constructed variate. One simple application is to the meta-analysis of independent studies of the same diagnostic test, illustrated on some data of Moses, Shapiro, and Littenberg (1993). A second application, to so-called vigilance data, is given, where ROC curves differ across subjects and modeling of the position along the ROC curve is of primary interest.
To investigate what is lost or gained in a psychiatric evaluation when it takes place via telepsychiatry we compared the interrater reliability between two psychiatrists interviewing 63 subjects in an observer/interviewer split configuration in telepsychiatry and same-room settings. The measures used were the BPRS and interviewer ratings from a semi-structured interview. Patients also rated their experience. There were some clear differences between the telepsychiatry and same-room evaluations. Despite these variations, diagnoses were as reliably made by telepsychiatry. Patient acceptance of telepsychiatry was high.
Metronidazole, used for prevention and treatment of infections in oral and maxillofacial surgery is frequently prescribed three times daily, but research into its pharmacokinetics has shown that a twelve hourly dosage regimen achieves and maintains therapeutic serum concentrations. No clinical data is available to support this and consequently a single blind, prospective, randomised trial was carried out to compare rates of postoperative infection following mandibular third molar excision under general anaesthesia. Sixty-two patients were randomly allocated to receive either 400 mg of metronidazole twice or three times daily for 5 days and all were assessed by the same surgeon for postoperative infection 7 days later. There was no statistically significant difference between rates of infection in either group and of potential side effects only nausea occurred statistically more frequently in the three times daily group. It would appear that a 12-hourly dose interval of metronidazole is no different from an 8-hourly dose interval, in prevention of local wound infection following minor oral surgery.
This paper concerns the statistical relationship between the risk of a fatality and the age and sobriety of drivers in New South Wales, Australia. The estimation of this relationship is based on fatal accident data from New South Wales and non-accident or control data from South Australia collected between the hours of 5.00 AM and 3.00 PM. The results are presented in new ways. In particular, tables of "accidents attributable to alcohol" and age specific intensity functions of "risk attributable to alcohol" may be an aid to policy making.
A case of toxic methaemoglobinaemia is presented, which followed the use of a local anaesthetic containing prilocaine (Citanest, Astra Pharmaceuticals Ltd) which was used to provide analgesia prior to the suturing of a facial laceration. Although this complication is well documented, this case is unusual in that it involved a neonate and was not produced by an overdose of prilocaine (the recommendations of the British National Formulary and the product monograph were followed). Explanations for the increased susceptibility of neonates and young infants to methaemoglobinaemia are presented together with the salient clinicopathological features. The diagnostic dilemmas and investigative procedures related to the condition are considered together with the various treatments available.
Although the colonic mucosa is one of the most rapidly proliferating epithelial tissues in the body, little is known about the factors that direct this proliferation. In this report we have studied the parameters of both a mitogenic and a clonogenic assay for detecting potential colonic growth factors (CGF). Using a colon carcinoma cell line (LIM1215), which has retained a number of the properties of normal colonic mucosa, we have assayed a range of mitogenic factors for CGF activity. 3H-thymidine incorporation by the LIM1215 cell line was stimulated by low concentrations of epidermal growth factor and basic fibroblast growth factor and, to a lesser extent, by higher concentrations of interleukin-1 and insulin-like growth factor 1. The cells did not respond to a range of other mitogens and lymphokines. Optimal clonogenic response in a soft-agar assay was obtained using a primary pituitary extract.
Angiotensinogen mRNA is found in many extrahepatic tissues, where it may participate in local angiotensin-generating systems. In this study we explore the feasibility of using anti-sense RNA to decrease angiotensinogen production in rat H4IIEC3 hepatoma cells. An amplifiable shuttle vector was modified to allow the production of high levels of stable anti-sense RNA from two regions of the mouse angiotensinogen gene under the control of the inducible sheep metallothionein promoter. Stably transformed, clonal cell lines expressing anti-sense RNA for angiotensinogen were isolated after selection with the aminoglycoside G418. Subsequently, the number of chromosomally integrated copies of the angiotensinogen anti-sense constructs was coamplified by methotrexate selection for dihydrofolate reductase activity carried on the shuttle vector. With a 20- to 30-fold induction of the anti-sense RNAs, the target angiotensinogen mRNA level was reduced to 25-30% of control values. The specificity of this effect was confirmed by showing no decrease in either beta-tubulin or neomycin phosphotransferase mRNA levels. Using tissue-specific promoters, it should be possible to direct these effects to specific organs in transgenic mice. However, in agreement with results from other groups, our findings suggest that it will not be possible to eradicate completely the target gene product using the anti-sense RNA strategy.
Murine epidermal growth factor (EGF), a 53 amino acid protein, has been modified by enzymic digestion, site-specific chemical reactions, and recombinant DNA technology. After trypsin digestion the EGF derivatives EGF1-48 (called EGF-T) and EGF1-45 (called EGF-T2) were separated from the residual EGF and the C-terminal pentapeptide by reversed-phase high-performance liquid chromatography. EGF-T competes for binding to EGF receptors with the same efficiency as EGF. The EGF-T2 derivative had no detectable receptor binding activity even at 100 nM. The in vitro mitogenic potencies of EGF and EGF-T for Balb/c 3T3 cells were indistinguishable. Treatment of EGF-T with carboxypeptidase Y yielded two derivatives, EGF-T-(des-Arg48) and EGF-T-des(Leu47-Arg48). There was only a 3-7-fold diminution in the binding efficiency and mitogenic potency for EGF-T-(des-Arg48). However, there was more than a 100-fold decrease in the binding efficiency and mitogenic activity of EGF-T-des (Leu47-Arg48). These results indicated that Leu47 is intimately involved in the formation of the ligand-receptor complex. Studies with a number of proteases indicated that the C-terminus of EGF was susceptible to enzymic digestion; however, the N-terminus appears to be folded into a conformation which prevents access to proteolytic digestion. Consequently, the N-terminus was modified by preparing an analogue with recombinant DNA technology. Oligonucleotides corresponding to EGF(3-48). Met3 Lys21 residues were ligated in frame to a beta-galactosidase expression vector. The beta-Gal-EGF fusion protein was cleaved with cyanogen bromide and EGF(4-48).Lys21 purified.(ABSTRACT TRUNCATED AT 250 WORDS)
Dupont investigated the advantages of doubling the one-sided P-value in conducting a two-sided test of independence in a 2 x 2 table and claimed that the main advantage was that, unlike the 'exact' P-value, small changes in the table resulted in small changes in the significance. He admitted that this practice had no obvious theoretical justification. In this paper, I take the view that repeated sampling properties should form the basis of any such justification. I develop an appropriate framework for studying P-values and show that doubling the one-sided P-value produces a biased test whenever the table is asymmetric. I show how one may derive a slightly more complicated P-value from a uniformly most powerful test. While there are difficulties in interpreting these P-values, I argue that, in principle, one should prefer the latter. In practice the difference between the two is typically less than 10 per cent (for the tables Dupont considered, the difference is of the order of 1 per cent) but with highly skew tables the difference can be much larger.
The complete amino acid sequence of basic FGF (146 residues) from ovine pituitary glands has been established. This has been achieved by the sequence analysis of subnanomole amounts of the intact molecule and of peptides derived by enzymatic digestions with clostripain, chymotrypsin, pepsin and Staphylococcus aureus V8 protease. Microbore HPLC, employing 1-2 mm i.d. columns, was used to purify, concentrate and buffer-exchange the FGF peptides. A novel application of ion-pairing chromatography was employed to isolate peptides which were not retained on conventional reversed-phase systems. There is only one positional difference between the ovine and bovine basic FGFs, but there are 3 positional differences between ovine and human basic FGFS.
The role of cyclic AMP in regulating the production of angiotensin converting enzyme (ACE) was investigated using cultured bovine aortic endothelial cells. Addition of dibutyryl cAMP [Bu)2cAMP) at 100 microM increased the ACE activity to 126% of control (P less than 0.005). This effect was blocked by either actinomycin D (0.1 microgram/ml) or cycloheximide (1.7 microM) indicating that RNA as well as protein synthesis was required for induction of the enzyme. After addition of (Bu)2cAMP, a lag period of 8 h was observed before increased ACE activity was detected. The stable analogues, 8-bromo cAMP (100 microM) and N6-monobutyryl cAMP (100 microM) also increased ACE activity but cAMP (100 microM) and O2-monobutyryl cAMP (100 microM) had no effect, in keeping with their susceptibility to phosphodiesterase in this system. Sodium butyrate (100 microM) was also inactive. The effect of (Bu)2cAMP on ACE was still observed in the presence of a maximal dose of dexamethasone, indicating that (Bu)2cAMP stimulates by mechanism(s) independent of the previously observed action of glucocorticoids on these cells. The phosphodiesterase inhibitor IBMX caused a dose-related increase in ACE activity with a threshold at 30 microM (P less than 0.05) and produced a 4-fold increase above control at 1 mM IBMX.
A method is developed for determining ligand-cell association parameters from a model-free analysis of data obtained with a flow cytometer. The method requires measurement of the average fluorescence per cell as a function of ligand and cell concentration. The analysis is applied to data obtained for the binding of fluoresceinated epidermal growth factor to a human epidermoid carcinoma cell line, A431. The results indicate that the growth factor binds to two classes of sites on A431 cells: 4 X 10(4) sites with a dissociation constant (KD) of less than or equal to 20 pM, and 1.5 X 10(6) sites with a KD of 3.7 nM. A derived plot of the average fluorescence per cell versus the average number of bound ligands per cell is used to construct binding isotherms for four sub-populations of A431 cells fractionated on the basis of low-angle light scatter. The four sub-populations bind the ligand with equal affinity but differ substantially in terms of the number of binding sites per cell. We also use this new analysis to critically evaluate the use of 'Fluorotrol' as a calibration standard in flow cytometry.