Biomedical subjects
Publications and source records attributed to D Houghton.
Pre-tracheal air cysts or aeroceles are rare complications of tracheostomy. This is believed to be the first reported case in an adult presenting with a pre-tracheal air cyst 12 years after a tracheostomy. Only three case reports in children have been reported to date. The pathogenesis and treatment options are discussed and a method of managing this condition is suggested.
BACKGROUND: Resistance to the action of parathyroid hormone (PTH) has been demonstrated in end-stage renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is unknown. However, altered regulation of cellular PTH/PTH-related protein (PTH/PTHrP) receptor (PTH1R) has been assumed to be important. METHODS: We have used in situ hybridization to examine PTH1R mRNA expression by osteoblasts in human bone and have compared the expression in high- and low-turnover renal bone disease, high-turnover nonrenal bone disease (healing fracture callus and Pagetic bone), and normal bone. Bone biopsies were formalin fixed, ethylenediaminetetraacetic acid decalcified, and paraffin wax embedded. A 1.8 kb PTH1R cDNA probe, labeled with 35S, was used, and the hybridization signal was revealed by autoradiography. The density of signal over osteoblasts was quantitated using a semiautomated Leica image analysis software package. RESULTS: The mean density of PTH1R mRNA signal over osteoblasts in renal high-turnover bone was only 36% of that found in nonrenal high-turnover bone (P < 0.05) and 51% of that found in normal bone (P < 0.05). Osteoblast PTH1R mRNA signal in adynamic bone from individuals with diabetes mellitus was 28% of normal bone (P < 0.05) and 54% of that found in renal high-turnover bone (P < 0.05). CONCLUSIONS: These results demonstrate a down-regulation of osteoblast PTH1R mRNA in end-stage renal failure in comparison to normal and high-turnover bone from otherwise healthy individuals, and provide an insight into the mechanisms of "skeletal resistance" to the actions of PTH.
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The possibility of reduction of numbers of fresh coumarin and normal plasmas has been studied in a multicentre manual prothrombin (PT) calibration of high international sensitivity index (ISI) rabbit and low ISI human reference thromboplastins at 14 laboratories. The number of calibrant plasmas was reduced progressively by a computer program which generated random numbers to provide 1000 different selections for each reduced sample at each participant laboratory. Results were compared with those of the full set of 20 normal and 60 coumarin plasma calibrations. With the human reagent, 20 coumarins and seven normals still achieved the W.H.O. precision limit (3% CV of the slope), but with the rabbit reagent reduction < 50 coumarins with 17 normal plasmas led to unacceptable CV. Little reduction of numbers from the full set of 80 fresh plasmas appears advisable. For maximum confidence, when calibrating the ISI of a new reagent, it would always seem worthwhile to use the full number of patients' and normal plasmas at each centre for the initial calibration, i.e. 60 fresh coumarin and 20 fresh normal plasmas. Smaller numbers should achieve the required precision with the lower ISI reagent.
An underlying assumption of the WHO orthogonal regression model for prothrombin time standardisation is that a single line describes the relationship between PT of abnormal and normal plasmas. The aim was to evaluate Tomenson's correction for lack of coincidence using the model of the ECAA human reagent with lyophilized plasma calibrations. Local ISI calibrations using ECAA lyophilized normal and abnormal plasmas were performed on coagulometers with the ECAA human thromboplastin. They gave a high incidence of non-linearity of the two calibration slopes. The mean percentage deviation from assigned values of the target coumarin plasmas coagulometer INR at 45 centres before local ISI correction was 16.6% and 11.9% respectively in two studies. After local ISI calibration. the unsigned deviation was reduced to 5.54% and 6.61% respectively. Tomenson's correction for non-linearity further reduced the mean deviation to 3.08% and 2.96% respectively in the two studies demonstrating the value of the procedure.
Artificially-depleted lyophilized plasmas and lyophilized coumarin plasmas were prepared and compared with fresh coumarin plasmas to assess their comparative reliability in local thromboplastin calibration using the manual prothrombin time (PT) technique. Their certified PT values were inserted in turn on the vertical axis in place of the PT obtained with fresh coumarin plasmas. PT results were obtained at eight ECAA national laboratories ('test centres') and inserted on the horizontal axis. The resulting thromboplastin calibration slopes were compared with conventional fresh coumarin plasma calibration slopes at the same 'test centres'. When 60 artificially-depleted plasmas were substituted for 60 fresh plasmas, the mean calibration slopes with the human plain International Reference Preparation (IRP) were 4.2% higher. For comparison with 20 lyophilized coumarins, three sets of 20 artificially-depleted plasmas were selected in sequential order from the 60. The lyophilized coumarin plasmas gave a mean deviation of 9.6% from the fresh plasma calibration slopes compared with values of 2.0%, 6.1% and 11.7% for the three sets of 20 depleted plasmas. Although both types of lyophilized plasma calibration slopes give measurable differences from conventional fresh plasmas, these may be regarded as acceptable in clinical terms.
International sensitivity index calibrations based on the W.H.O. recommended method depend on orthogonal regression analysis. As this is not readily available in statistical packages, comparison has been made with simple linear regression analysis in a study of coagulometer effects on the International Normalized Ratio (INR) at 155 European centres. Sets of seven lyophilized normal and 20 lyophilized artificially depleted abnormal plasmas were provided with five coumarin test plasmas and two European Concerted Action on Anticoagulation reference thromboplastins (low International Sensitivity Index (ISI) human and high ISI rabbit). Local ISI based on the artificially depleted lyophilized plasmas using conventional orthogonal regression gave good correction for local coagulometer effects on the human reagent and minimal correction with the rabbit reagent INR. Results were considerably worse after attempts at correction using calibration based on linear regression analysis with both reagents. The results indicate that calibration of coagulometer prothrombin time systems using simple linear regression is not appropriate.
Many papers have been written on the effect of age on survival from cancer and a number of these papers have concentrated on cancer of the head and neck. The literature is fairly evenly split between those studies that claim that the young patient has a better chance of survival and those that suggest the older patient has a better chance of survival. The present study investigates 2647 patients with histologically proven squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. The tumour-specific 5-year survival of patients with head and neck cancer from the third decade through to the seventh decade at presentation was 54%, whereas this figure dropped to 44% for the eighth, ninth and tenth decades. This difference was statistically significant (P = 0.0001). When the patients in the third to seventh decades of presentation were compared with those from the eighth to tenth decades, it was found that older patients tended to have significantly more advanced disease at the primary site and fewer neck node metastases when compared with younger patients at presentation. These differences were confirmed by multiple logistic regression. Multivariate analysis of survival confirmed that advanced age was associated with poor survival (P = 0.0001). Whilst patients with head and neck cancer in their eighth, ninth and tenth decades fared worse than younger patients, their mean tumour specific survival at 5 years was in the region of 44%, which makes treatment worthwhile, certainly in selected cases.
The minimum requirement of lyophilized plasma samples for a reliable International Sensitivity Index (ISI) was assessed by calibrations based on reducing numbers from a maximum of 60 depleted and 20 plasma samples from patients receiving coumarin using a manual technique and low ISI thromboplastin. The probability of achieving an international normalized ratio (INR) result within a clinically important range of 20% deviation has been assessed at European Concerted Action on Anticoagulation (ECAA) national laboratories in calibrations of ECAA reference thromboplastin against the certified prothrombin time (PT) with a reference thromboplastin. With conventional orthogonal regression using a certified PT and linear regression using certified INR, deviations and the coefficient of variation of the calibration slope increased with reduced numbers. The INR deviations became marked when the number of abnormal plasma samples was reduced to fewer than 20. Calibrations of 3 abnormal plasma samples and 1 lyophilized normal plasma sample gave a high incidence of deviations greater than 10% with an INR of 3.0. The study demonstrates that with both methods of analysis, an optimum minimum number of lyophilized plasma samples is needed for a reliable local ISI.
AIM: To assess reliability of like to like and cross species calibrations using two types of certified freeze dried plasma calibrants--artificially depleted of vitamin K clotting factors, and from coumarin treated patients. METHODS: Six ECAA national control laboratories provided certified values for the freeze dried plasmas in terms of the human plain international reference preparation (IRP) (BCT/441) with the manual prothrombin time technique. Eight other ECAA national laboratories determined international sensitivity index (ISI) values in full fresh plasma same species and cross species WHO calibrations against a low ISI human IRP (BCT/441) of the ECAA low ISI human thromboplastin and high ISI ECAA rabbit thromboplastin. Parallel calibrations were performed using the certified values. RESULTS: Calibrations on fresh plasmas of the human ECAA reference thromboplastin (stated ISI = 0.95) gave ISI of 0.957 against the human IRP and 1.66 against the rabbit IRP. The ECAA rabbit (stated ISI = 1.67) gave an identical value on the fresh plasma calibration v the human IRP. With freeze dried depleted plasmas certified in terms of the human IRP, the ISI of the ECAA human was 1.01, but the ECAA rabbit (stated ISI = 1.67) gave a low ISI of 1.47. The freeze dried coumarin plasmas gave an ISI of 0.943 for the ECAA human but only 1.493 for the ECAA rabbit. CONCLUSIONS: Fresh plasmas give reliable ISI when calibrating thromboplastins in same species and cross species calibrations. Freeze dried plasmas certified in terms of a single IRP, whether artificially depleted or of coumarin plasma origin, cannot be used for calibration of dissimilar thromboplastins.
Establishing the mean normal prothrombin time (MNPT) from fresh samples for prothrombin ratios and INR often presents difficulty in selection and collection of donors. A set of seven lyophilized normal plasmas has therefore been prepared at the ECAA Central Facility and studied at 143 laboratories in sixteen European states using coagulometers in serial field exercises. All centres tested either the high ISI ECAA rabbit or low ISI ECAA human reference thromboplastin. The MNPT of fresh plasmas and means of the lyophilized samples were closely comparable with most routine rabbit thromboplastins. Using human thromboplastins means with the lyophilized normals were marginally but significantly longer and with the bovine Thrombotest significantly shorter than the MNPT of fresh plasmas causing alterations in INR. There was no appreciable effect on INR of 2.5 and 3.5 when lyophilized normals were substituted for fresh normals with the rabbit reagents.
Local calibration studies have been performed with lyophilized plasmas at 155 European laboratories to assess coagulometer effects on manual ISI of ECAA thromboplastins (low ISI human recombinant and high ISI rabbit brain). Common sets of 7 normal and 20 artificially depleted lyophilized plasmas were tested with the thromboplastins in the routine local coagulometers. With the human reagent, marked lowering of the manual ISI resulted with most coagulometers, which was associated with disproportionate shortening of the normals. Where this shortening did not occur, there was little coagulometer effect on the ISI. With the rabbit reagent, proportionate shortening with both normal and abnormal plasmas occurred in most instruments with little effect on ISI. INR correction by local ISI assignment appeared successful with the ECAA human reagent. There was negligible INR correction from local calibration of the ECAA rabbit reagent in coagulometers where thromboplastin ISI were unchanged from the ECAA established manual values.
Four cases of serious MRSA wound infection following head and neck surgery have been identified. One patient died. At post mortem a mediastinal abscess containing MRSA was found to have eroded into the innominate artery causing fatal haemorrhage. The other three suffered serious wound infections, two requiring further surgery. Once MRSA had been identified they were treated with intravenous teicoplanin and all made a full recovery.
A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regression assumes error with both reference and local results. The reliability of local INR derivation using lyophilized plasmas has been assessed in a collaborative study. INR from conventional fresh plasma International Sensitivity Index (ISI) calibrations have been compared with INR from calibrations with two types of lyophilized plasma, artificially depleted and coumarin. Although calibration slopes differed with the two types of analysis and the different lyophilized plasmas, both gave reasonable approximations to fresh plasma ISI calibrations. With orthogonal regression the overall percentage INR deviation was 5.25% with the artificially depleted plasmas and 6.85% for the results with lyophilized coumarins. With the linear regression, deviation was 8.40% for the artificially depleted plasmas and 5.05% for coumarin-treated patients' lyophilised-plasma. The simpler regression method appears to be worthy of further study as the present report has demonstrated that if the calibrant plasmas are accurately certified with the thromboplastin International Reference Plasma (IRP) results approximate to the conventionally determined INR using the manual PT technique. Coagulometers require further assessment.
Two candidate ECAA reference preparations have been calibrated in a multicentre exercise at 14 representative national laboratories to provide reference thromboplastin for a large field study in 16 European countries. Two preparations were required because of the established differences in ISI arising from the two main routes of calibration via rabbit and human IRP. To be comparable with working reagents in everyday use a human plain recombinant reagent of low ISI and a rabbit plain preparation of moderately high ISI were selected. A precise calibration of the two candidate preparations has been achieved with the manual PT technique and an ISI of 0.95 (SE 0.0078) for the human reagent and 1.67 (SE 0.0322) for the rabbit reagent.
The mean normal prothrombin time (MNPT) based on the fresh plasma of 20 healthy individuals is the recommended way to derive a normal value for the prothrombin ratio. This is generally believed to give a reasonable representation of the normal in the local population, but there may be difficulty in obtaining a good representative sample in some centres. The alternative of a uniform lyophilized 'normal' plasma has been suggested. The comparative value of a widely used commercial 'normal' plasma and the MNPT has been assessed in an international study at 37 centres. Two common thromboplastins were tested using the local coagulometer methods. The variability of the results and their relative performance in local thromboplastin calibration to derive the International Sensitivity Index (ISI) were assessed. The reliability of the two types of normal in local system ISI calibration with different lyophilized plasma calibrants has also been tested. When the lyophilized 'normal' was substituted for the MNPT in ISI determination no appreciable difference in the degree of correction for coagulometers effects on International Normalized Ratios was found.
The health professions, including optometry, are facing a declining applicant pool. The American Optometric Association has taken steps to address the challenge of increasing the pool of qualified applicants to the schools and colleges of optometry. However, the most significant factor in the process will be the efforts of individual AOA members.
The redefined roles within the NHS, and the changed organisational structures required to meet the challenges of the purchaser/provider environment, are bringing an unprecedented state of flux between organisations and their staff. New roles and altered responsibilities, more fluid organisational structures, all increase the risk of individuals being placed in inappropriate positions. Each one of these mismatches, argue Michael Church and Derek Houghton, represents a misuse of our most valuable resource--people, and is a cost or waste for the organisation.