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Biomedical subjects

R Mitchell

Publications and source records attributed to R Mitchell.

At least 37 records · Page 2Linked to original sources

Selective use of tracheostomy in surgery for head and neck cancer: an audit.

This retrospective study was designed to define the role of tracheostomy in the operative treatment of patients with cancers of the head and neck. The subjects were 51 patients who underwent neck dissection with resection of the tumour and repair during the period January 1992-December 1994, out of a total of 109 patients who were treated for cancers of the head and neck during that time. Three patients required tracheostomies, two of which were done preoperatively, and one immediately postoperatively for respiratory distress. There were no operative deaths. Morbidity included wound infection (n = 2), chest infection caused by Haemophilus influenzae (n = 1), transient fever associated with blood transfusion (n = 5), and transient fever of no obvious cause (n = 3). Median hospital stay was 10 days (range 4-38). Patients undergoing operations for cancers of the head and neck do not require routine tracheostomy. Further research on how to select patients who will need tracheostomy is necessary and is being done.

Adult

Survival of patients who needed salvage surgery for recurrence after radiotherapy for oral carcinoma.

OBJECTIVE: To find out how long patients with oral carcinoma survived after the primary tumour had been treated by radiotherapy and who required salvage surgery for recurrence; to see if there were any significant differences in age, sex, site, size, and histology of the tumours in relation to survival; and to see if the time of the recurrence had any effect on the survival. DESIGN: Retrospective analysis of case notes. SETTING: Teaching Hospital Scotland. SUBJECTS: 370 consecutive patients, 187 (51%) of whom were initially treated by radiotherapy; 58 of the 187 (31%) developed a recurrence that was considered suitable for salvage surgery. RESULTS AND CONCLUSIONS: 43/58 patients had died and 15 patients were still alive at the time of the study, the median (range) survival of the group was 21 (6-89) months compared with 72 (19-212) months, respectively (P = 0.0001). Other significant difference included age at presentation for men (P = 0.004), and the increased likelihood of survival if the initial site of the tumour was the tongue (P = 0.02). There was also a highly significant correlation between time to recurrence and survival amongst those who died (P = 0.002). A short recurrence time may suggest a less radical surgical salvage option if reduced survival is likely. Why there should be such an association is unknown.

Adult

Fiber-reinforced polymeric composites are susceptible to microbial degradation.

A mixed culture of fungi, enriched from degraded polymeric materials, formed biofilms on coupons of fiber-reinforced polymeric composites (FRPCs). They grew actively in aqueous extracts of the composites under ambient conditions. The data indicate that the fungi utilized the resins or fiber chemical sizing as carbon and energy sources. A progressive decline in impedance from above 10(7) Ohms to below 10(8) Ohms was detected in the inoculated FRPC panels by electrochemical impedance spectroscopy (EIS) after 179 days of incubation, but not on the sterile controls. The degradation proceeds through an initial ingress of water into the resins, followed by degradation of bonding between fiber surfaces and resins and finally separation of fibers from the resins. At the end of EIS study, the extent of disbonding in the inoculated composite was greater than the control observed by scanning electron microscopy. These results suggest that the composite materials are susceptible to microbial attack by providing nutrients for growth.

Biodegradation, Environmental

Effect of low dose oxandrolone and testosterone treatment on the pituitary-testicular and GH axes in boys with constitutional delay of growth and puberty.

OBJECTIVE: To investigate the effect of low dose oxandrolone and testosterone on the pituitary-testicular and GH-IGF-I axes. DESIGN: Prospective double-blind placebo-controlled trial. PATIENTS: Sixteen boys with constitutional delay of growth and puberty (CDGP) with testicular volumes 4-6 ml were randomized to 3 months treatment: Group 1 (n = 5), daily placebo: Group 2 (n = 5), 2.5 mg oxandrolone daily or Group 3 (n = 6), 50 mg testosterone monthly intramuscular injections with assessment (growth, pubertal development and overnight hormone profiles) at 0, 3, 6 and 12 months. MAIN OUTCOME MEASURES: LH and GH profiles (15-minute samples) were analysed by peak detection (Pulsar), Fourier transformation and autocorrelation. Testosterone levels were measured hourly and insulin, SHBG, IGF-I, and IGFBP-3 levels at 0800 h. Statistical analysis was by multivariate analysis of variance for repeated measures. RESULTS: LH and testosterone parameters increased significantly with time in all 16 (LH AUC, P < 0.001; peak amplitude, P = 0.02; number of peaks, P = 0.02; testosterone AUC, P = 0.02; morning testosterone, P = 0.002). In Group 2, however, LH and testosterone parameters decreased at 3 months followed by a rebound increase at 6 and 12 months. SHBG levels were markedly reduced at 3 months (P = 0.006) and a wider range of dominant GH frequencies was present although GH AUC was not increased until 6 months, with an increase in GH pulse frequency but not amplitude. IGF-I levels were increased at both 3 and 12 months. In Group 3, pituitary-testicular suppression was not apparent, but GH levels increased with an increase in GH amplitude at 3 and 12 months. CONCLUSION: Oxandrolone transiently suppressed the pituitary-testicular axis and altered GH pulsatility. Testosterone increased GH via amplitude modulation.

Adolescent

Juvenile chronic arthritis: diagnosis and management of tibio-talar and sub-talar disease.

The aim of this study was to compare clinical evaluation of the site of hindfoot synovitis with contrast-enhanced magnetic resonance imaging (MRI) findings in children with juvenile chronic arthritis (JCA), and to evaluate the efficacy of selective guided intra-articular steroid injections. Thirteen symptomatic ankles of 11 consecutive JCA patients were examined clinically and with contrast-enhanced MRI. Pannus was demonstrated on MRI in both tibio-talar and sub-talar joints in 10 ankles, in the tibio-talar joint only in one ankle and in neither joint in two ankles. Correlation of clinical and MRI findings was good for the tibio-talar joint with concordance in 11/13 cases. Correlation was poor for the sub-talar joints. Of the 10 sub-talar joints shown to have pannus on MRI, only two were thought to have had definite clinical evidence of synovitis. Guided intra-articular steroid injection resulted in at least 6 months remission in 6/9 ankles compared with 1/10 ankles which had had previous unguided injections. We therefore recommend the use of image guidance for intra-articular triamcinolone hexacetonide injection in children with hindfoot synovitis.

Adolescent

Nurse-managed healthcare. New York's Community Nursing Organization.

The Visiting Nurse Service of New York's Community Nursing Organization was developed to test the effectiveness of community-focused nursing case management services with elderly enrollees in a capitated reimbursement system. After 3 years of operation, it is evident that the long-term relationship between the nurse and the enrollee was the key to financial and clinical success.

Aged

The gunner with the silver mask: observations on the management of severe maxillo-facial lesions over the last 160 years.

We would like to present a case of severe maxillo-facial trauma occurring over 150 years ago. The case involves a French artillery gunner, Monsieur Alphonse Louis, who received shrapnel injuries from an exploding shell at the Siege of Antwerp in 1832. He sustained near fatal injuries. The fact that he survived is probably due to his rapid evacuation from the battle site, as the French did not like to leave their wounded lying in 'no man's land', prompt surgery and subsequent expert medical and nursing care. M. Louis' maxillo-facial injuries included loss of the entire mandible. As a consequence, the patient had a grotesque appearance and was unable to eat or talk properly. At this time the surgeons of the day had no specialist knowledge of how to reconstruct the lower jaw. Where specialist knowledge or facilities were absent, then as now, improvisation was called for. A silversmith was duly approached and asked to construct a mask to act as a replacement for the deficient lower face. We describe here what an excellent cosmetic and functional result the mask gave, and how it led to the patient being successfully rehabilitated. Almost a century later, during the First World War, pioneering work by Major Harold (later Sir Harold) Gillies and his colleagues led to the first attempts at anatomical mandibular reconstruction. His patients, like M. Louis, were soldiers injured in battle. We will describe his techniques and compare them with how this problem is approached in the modern era, although most reconstructive surgery to the maxillo-facial region these days follows the removal of comparably extensive areas of soft tissue and bone as a result of invasive tumour.

Europe

Effect of phorbol 12, 13-dibutyrate on ligand binding, enzyme activity and translocation of protein kinase C isoforms in the alpha T3-1 gonadotrope-derived cell line.

The effect of incubating alpha T3-1 cells with phorbol 12,13-dibutyrate (PDBu) on the protein kinase C (PKC) isoform content (predominantly alpha, epsilon and zeta isoforms) was assessed by immunoblotting, enzyme activity assay and [3H]PDBu binding. After exposure to PDBu for 17 h the immunoreactivity detected for both PKC alpha and PKC epsilon had disappeared from cytosol and had increased slightly in membranes. Immunoreactivity for PKC zeta was present as two bands in cytosol; after PDBu treatment both bands decreased in intensity, the higher molecular weight band more than the lower. The lower molecular weight band corresponded with a component of constitutive PKC activity eluting from DEAE cellulose that was defined by inhibition of basal activity with GF 109203X or H7. Investigation of very short treatment times with PDBu using binding, immunoblot and activity measurements (in the presence/absence of Ca2+) indicated that translocation of PKC alpha and epsilon was very rapid-detectable by 10 sec, maximal within minutes. Reduction of these isoforms in membranes took much longer, and was not apparent up to 150 min. The immunoblot data for PKC zeta in cytosol showed no detectable effect of PDBu treatment on the low molecular weight band up to 150 min although it was reduced at 17 h. Translocation of the upper band was detectable at 10 sec but this band may have resulted from cross-reaction with other PKC isoforms. The constitutive activity and low molecular weight ("authentic') PKC zeta immunoreactivity were partially affected after long exposure only, suggesting an action of PDBu on PKC zeta secondary to activation of the other PKC isoforms. An endogenous receptor agonist, luteinising hormone-releasing hormone (LHRH), was also used to assess by immunoblotting, translocation of the PKC isoforms. Although all the isoforms did translocate from cytosol to membrane fractions, they did so with distinctly different time courses: PKC epsilon moved more rapidly than PKC zeta which appeared to translocate more quickly than PKC alpha. After downregulation of the responsive PKC isoforms with PDBu, the remaining PKC zeta was not translocated by LHRH.

Animals

Separation of H7-resistant protein kinase C isoforms from gonadotroph-derived alpha T3-1 cells.

Certain physiological events in anterior pituitary tissue are regulated by protein kinase C that is relatively resistant to the inhibitor, H7. In the present studies we have shown that two H7-resistant protein kinase C activities may be isolated from (pituitary) gonadotroph-derived alpha T3-1 cells using hydroxyapatite chromatography. These activities have the characteristics of PKC zeta and an apparently novel PKC isoform. The availability of clonal alpha T3-1 cells will facilitate investigations of the pituitary events.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

MRI demonstration of arachnoiditis in cauda equina syndrome of ankylosing spondylitis.

The cauda equina syndrome is a rare but well-recognised complication of longstanding ankylosing spondylitis, usually presenting when the joint disease is quiescent. The clinical and radiological findings in a patient with only a 3-year history, in whom the onset of joint and neurological symptoms was apparently simultaneous, are presented. MRI revealed characteristic expansion of the lumbar spinal canal with scalloping of the pedicles, laminae and spinous processes, related to numerous posterior dural diverticula. The quantity and extent of such diverticula are unusual. We demonstrated adherence of individual nerve roots to the arachnoid surface of these diverticula and to each other. In a second patient, with a much longer history of both ankylosing spondylitis and cauda equina syndrome, MRI again showed florid, multilocular dural ectasia, marked irregularity and thickening of nerves, and adherence to the dural diverticula. These cases provide evidence for the role of arachnoiditis in the pathogenesis of the cauda equina syndrome of ankylosing spondylitis.

Aged

Blood alcohol and cardiac arrest.

Patients who suffer a cardiac arrest with alcohol present in their blood may, theoretically, differ from patients who arrest in the absence of alcohol. Alcohol may induce certain lethal arrhythmias, deter strenuous resuscitation in the pre-hospital phase and influence the effectiveness of resuscitative manoeuvres. In this study, 150 patients presenting to an Accident and Emergency department with cardiac arrest were tested for the presence of alcohol in their plasma. 49 patients had detectable plasma alcohol and analysis of their pre-hospital resuscitation revealed no significant differences when compared with the 101 patients in whom no alcohol was detected. No particular arrhythmia predominated in the alcohol group, and patients who had alcohol detected in their blood were just as likely to be successfully resuscitated, in terms of both restoration of spontaneous circulation and survival to hospital discharge. The effect of significantly elevated plasma alcohol levels on cardiac arrest outcome remains unclear, however, as only 7/150 patients had plasma alcohol levels above the legal driving limit.

Adolescent

Radiation exposure during ERCP: effect of a protective shield.

OBJECTIVES: To measure the radiation exposure to endoscopists, patients, and assistants during diagnostic and therapeutic ERCP and to assess the effect of a protective lead shield. Radiation dose with and without the protective lead shield was mapped in our standard fluoroscopy room. MATERIALS AND METHODS: Twenty patients undergoing ERCP were selected for this study. Radiation exposure of endoscopists with and without a protective shield was monitored by digital dosimeter. Radiation exposure for diagnostic procedures was correlated with that of therapeutic procedures. RESULTS: Endoscopists were exposed to 2.5 mR without the protective shield, but exposure was reduced to an average of 0.27 mR per procedure with the shield. Endoscopists received an average of 1.5 mR per diagnostic ERCP and 3.17 mR per therapeutic ERCP without the shield. When using the protective shield, however, those numbers were reduced to an average of 0.25 mR per diagnostic procedure and 0.28 mR per therapeutic procedure. Radiation exposure to endoscopic assistants, who were not shielded, averaged 0.56 mR per procedure. CONCLUSION: Amount of radiation exposure to occupational personnel during ERCP was related to duration of fluoroscopy and type of procedure. Radiation exposure to endoscopists can be significantly reduced by the use of a protective shield. Medical assistants received less radiation than did endoscopists because the assistant's position was more distant from x-ray sources.

Adult

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.

Adenomatous Polyposis Coli

Albendazole resistance in Giardia is correlated with cytoskeletal changes but not with a mutation at amino acid 200 in beta-tubulin.

Albendazole resistance was induced in three different Giardia cultures following growth in successively increasing amounts of drug. One of the lines was previously resistant to high levels of metronidazole and was able to grow in 2 microM albendazole. The other two survived exposure to 0.8 microM, while normally lethal levels of albendazole against Giardia in vitro were around 0.1-0.2 microM. Albendazole-resistant Giardia were cross-resistant to parbendazole. Major chromosome rearrangements were evident in the line resistant to 2 microM albendazole and IFA with antitubulin antibody indicated differences in the cytoskeleton, particularly the median body, between sensitive and resistant lines. This implicates the cytoskeleton in the mechanism of resistance. Substitution of Tyr for Phe is a consistent beta-tubulin amino acid change in the benzimidazole-resistant helminths and fungi so far analyzed. PCR primers were designed from the published Giardia beta-tubulin gene sequence and spanned the region encoding Phe at position 200. Sequence data from albendazole-resistant Giardia demonstrated that the beta-tubulin gene did not carry a mutation in the codon for amino acid 200. These data suggest that Phe at position 200 in beta-tubulin is not necessary for benzimidazole resistance.

Albendazole

Recombinant human luteinizing hormone: a partial physicochemical, biological and immunological characterization.

The aim of this study was to partially characterize the glycoform composition of a recombinant human luteinizing hormone preparation (rhLH; Serono), an early version of the material (LHadi) which is currently being assessed for clinical application. Specifically, the charge (pl) and internal carbohydrate complexity of this rhLH was examined and compared with that of an alternative commercially available form of recombinant LH (Crystal Chem) and a pituitary International Reference Preparation (IRP). All preparations were separated by charge by chromatofocusing them on a pH gradient (7-4) using a 4 ml mono-P column is conjunction with a fast performance liquid chromatography system and by complexity of the oligosaccharide structures using concanavalin A (con-A) lectin affinity chromatography. LH in both the unfractionated and fractionated material was assessed by immunoradiometric assay (IRMA, I-LH) and by the in-vitro Leydig cell bioassay (B-LH). Both assays were calibrated against IRP 80/552. The in-vitro biopotency of the preparations was 18187 (Serono rhLH), 12063 (Crystal Chem rhLH) and 6658 (80/552) IU/mg; biological:immunological ratios were 1.14 (80/552), 1.90 (Crystal Chem rhLH) and 1.99 (Serono rhLH). However, similar qualitative data were obtained by both bioassay and immunoradiometric assay following fractionation, with the median pl of the bioactive LH in the preparations being 5.5 (24% > pH 6), 5.52 (18% > pH 6) and 4.97 (0% > pH 6) for the Serono, Crystal Chem and pituitary preparations respectively. Further all three contain < 1% of the complex carbohydrate structures and between 36-44% and 56-63% of the intermediate and simple forms of bioactive LH. In conclusion, the Serono recombinant LH preparation has a higher in-vitro bioactivity and is more basic than the other two preparations although the complexity of its carbohydrate moities appears to be similar.

Animals

Internal carbohydrate complexity of the oligosaccharide chains of recombinant human follicle stimulating hormone (Puregon, Org 32489): a comparison with Metrodin and Metrodin-HP.

Glycoforms of recombinant human follicle stimulating hormone (rhFSH) (Org 32489, Puregon) were characterized using concanavalin A lectin affinity chromatography to reveal information about the internal carbohydrate complexity (extent of carbohydrate side-chain branching) of the preparations. The rhFSH glycoforms were measured by radioimmunoassay and a two-site immunoradiometric assay and compared with those in two urinary preparations (Metrodin and Metrodin-HP) used in assisted reproduction programmes and a urinary FSH international standard 70/45 (uFSH IS 70/45). Similar data were obtained with both assays; rhFSH had 6% complex internal carbohydrate structures compared with 22-27% for Metrodin, Metrodin-HP and uFSH. The proportion of simple carbohydrate structures was also different, with rhFSH having 18.5 compared with 4.5-9.3% for Metrodin, Metrodin-HP and uFSH. A linear relationship was observed between the percentage glycoforms with an isoelectric point (pl) < 4 and the log percentage simple forms (logarithmic regression; r = 0.93) indicating a direct relationship between carbohydrate complexity and charge heterogeneity. In summary, rhFSH contains fewer complex forms and an increased proportion of simple carbohydrate structures in comparison with Metrodin, Metrodin-HP and IS 70/45.

Carbohydrates