Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay

The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory.     

Review: Clinical,genetic and neuroimaging features of frontotemporal dementia

Frontotemporal dementia (FTD) is a heterogeneous group of disorders causing neurodegeneration within a network of areas centred on the frontal and temporal lobes. Clinically, patients present with behavioural symptoms (behavioural variant FTD) or language disturbance (primary progressive aphasia), although there is an overlap with motor neurone disease and atypical parkinsonian disorders. Whilst neuroimaging commonly reveals abnormalities in the frontal and temporal lobes, a closer review identifies a more complex picture with variable asymmetry of neuronal loss, widespread subcortical involvement and in many cases more posterior cortical atrophy. An autosomal‐dominant genetic disorder is found in around a third of people with mutations in progranulin, C9orf72 and the microtubule‐associated protein tau being the commonest causes. In the other two‐thirds, the disorder is sporadic, although recent genome‐wide association studies have started to identify genetic risk factors within this group. Much of this knowledge has been understood only in the past 10 years and so this review will discuss the current knowledge about the clinical, genetic and neuroimaging features of FTD.     

Neurohydatidosis

Early and non‐invasive evaluation of hydatid infestation of brain and spine is of paramount importance, especially in endemic areas. We present a spectrum of imaging findings in neurohydatidosis with a brief review of literature.     

High frequency oscillation in newborn infants with respiratory failure

Objective: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV).
Methodology Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation.
Results Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights <1500g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight >1500g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing <1500g who received HFOV in the first week of life developed periventricular haemorrhage.
Conclusion The initial results of HFOV for severe respiratory failure were encouraging although a learning curve was encountered with its introduction.     

Private water wells in Minnesota: recommended tests for contaminants

Approximately 1.25 million Minnesotans get their drinking water from private wells. These wells may contain coliform bacteria, nitrate, arsenic, and other contaminants that can pose health risks. In order to ensure the safety of drinking water, the Minnesota Department of Health recommends that well owners test for such contaminants and perform periodic checks of the physical condition of the well. Health officials also recommend that unused or abandoned wells be properly sealed to prevent contamination of ground water.     

Hypersensitivity pneumonitis associated with mushroom worker's lung: an update on the clinical significance of the importation of exotic mushroom varieties

Hypersensitivity pneumonitis remains an important industrial disease in mushroom workers. It has a significant morbidity, and early diagnosis and removal from exposure to the antigen are critically important in its management. Recently, several new allergens have been described, particularly those from mushroom species originating in the Far East, which are of clinical significance to workers occupationally exposed to such allergens in cultivation, picking, and packing of commercial mushroom crops. Importing of exotic mushrooms including Shiitake is common in EU countries, and some of the exotic species of mushrooms are cultivated for local markets. This practice may contribute to an increase in clinical cases of mushroom hypersensitivity pneumonitis. This update reviews the recent literature and examines changing trends of mushroom worker's lung, with increased movement of commercial product and labour markets worldwide.     

Measurement of the consistency of patellar-tendon-bearing cast rectification

The quality of fit of a trans-tibial patellar-tendon-bearing (PTB) socket may be influenced by consistency in casting, rectification or alignment. This paper quantifies, for the first time, the variations in the rectified casts between two experienced prosthetists and the variation between the rectified casts of each individual prosthetist. Prosthetists A and B observed the hand casting of a typical trans-tibial amputee. Each prosthetist was supplied with 5 previously measured duplicated plaster models. The two prosthetists rectified the supplied plaster models based on their own interpretation of basic rectification guidelines. Both prosthetists operated in isolation. The re-measured rectified plaster model data was compared with the unrectified data. The extent of rectification at each of 1800 locations per plaster model was calculated. In zones of major rectification, the mean difference between prosthetists was quantified as 2mm and the standard deviation (SD) about that mean was +/- 1mm for each prosthetist. The co-ordinates of the apex of the fibular head for the 10 modified casts indicated that the maximum variation was in the axial direction with a SD of 4.3mm for prosthetist A and a SD of 2.8mm for prosthetist B. The lengths of the 5 plaster models rectified by prosthetist A indicated a SD of 0.2mm whereas the lengths of the 5 plaster models rectified by prosthetist B indicated a SD of 2.9mm.     

Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint

The efficacy of ropivacaine 100 mg (5 mg ml^–1),150 mg (7.5 mg ml^–1) and 200 mg (10 mg ml^–1)and bupivacaine 100 mg (5 mg ml^–1) givenby intra-articular injection into the knee after the end ofsurgery was studied in 72 ASA I–II patients scheduledfor elective knee arthroscopy under general anaesthesia in arandomized, double-blind study. Kapake (paracetamol 1 gand codeine 60 mg) was given as a supplementary analgesic.Pain scores were assessed 1–4 h after surgery and a verbalrating scale of overall pain severity was assessed on secondpostoperative day. Ropivacaine or bupivacaine concentrationswere determined in peripheral venous plasma up to 3 h afterinjection in eight patients in each group. Verbal rating painscores were lower with ropivacaine 150 mg compared withbupivacaine 100 mg (P<0.05). There was a tendency forlower analgesic consumption and pain scores with all doses ofropivacaine (not significant). The mean (SD) maximum total plasmaconcentrations of ropivacaine were 0.64 (0.25), 0.78 (0.43),and 1.29 (0.46) mg litre^–1 after 100, 150 and200 mg. The corresponding unbound concentrations were 0.018(0.009), 0.024 (0.020) and 0.047 (0.022) mg litre^–1.Both were proportional to the dose. The maximum total concentrationafter bupivacaine 100 mg was 0.57 (0.36) mg litre^–1.The time to reach maximum plasma concentration was similar forall doses and varied between 20 and 180 min. All concentrationswere well below the threshold for systemic toxicity. Br J Anaesth 2001; 87: 570–6