The reproducibility of assessing radiological reporting: studies from the development of the General Medical Council's Performance Procedures.

OBJECTIVES: To investigate the reproducibility of peer ratings of consultant radiologists' reports, as part of the new General Medical Council (GMC) Performance Procedures. DESIGN: An evaluation protocol was piloted, used in a blocked, balanced, randomized generalizability analysis with three blocks of three judges (raters), each rating 30 reports from 10 radiologists, and re-rated to estimate intrarater reliability with conventional statistics (kappa). SETTING: Rating was performed at the Royal College of Radiologists. Volunteers were sampled from 23 departments of radiology in university teaching and district general hospitals. PARTICIPANTS: A nationally drawn non-random sample of 30 consultant radiologists contributing a total of 900 reports. Three trained and six non-trained judges were used in the rating analysis. RESULTS: A protocol was generated that was usable by judges. Generalizable results would be obtained with not less than three judges all rating the same 60 reports from a radiologist. CONCLUSIONS: Any assessment of performance of technical abilities in this field will need to use multiple assessors, basing judgements on an adequate sample of reports.

Lymphocyte 5'-ectonucleotidase: an indicator of oxidative stress in humans?

Lymphocytic 5'-ectonucleotidase (NT) activity previously has been shown to be reduced in patients with a high pro-oxidant state. This study shows that NT activity is decreased in vitro by exposure to superoxide anions and that ascorbate protects against this effect. Also, a putative high pro-oxidant state in vivo, as indicated by low tissue ascorbate levels, resulted in a significant decrease in NT which an antioxidant intake normalized. These results taken together suggest that NT is sensitive to superoxide anion and that it may be a good marker of a pro-oxidant state in humans.

Age-related outcome for peripheral thrombolysis.

OBJECTIVES: To investigate the age-related outcome of peripheral thrombolysis and determine for which patient group this treatment is worthwhile. DESIGN AND METHODS: A combined retrospective and prospective analysis of consecutive patients undergoing thrombolysis for acute lower-limb ischaemia was made with respect to age-related outcome and other risk factors. RESULTS: One hundred and two patients underwent thrombolysis for acute limb ischaemia. In the under 60 age group there was a 40% amputation rate. Seventy-three per cent of this group smoked. In the over 80 age group, the amputation rate was 15% and only 8% were smokers. CONCLUSION: Advancing age is not an adverse risk factor for thrombolysis which appears to be safe and effective in this patient group. There is a high incidence of smoking in the younger age group (< 60 years), in whom failed thrombolysis frequently leads to amputation.

The effect of depression in an animal model on 5'-ectonucleotidase, antibody production, and tissue ascorbate stores.

The learned helplessness model of depression in rats was tested. It was hypothesized that 5'-ectonucleotidase (NT), ascorbate, and antibody to sheeps' red blood cells (SRBC) are significantly reduced in rats who experienced uncontrollable shock, compared with rats who did not receive shock or could control it. During a learned-helplessness manipulation, antibody response to SRBC and NT values were unaffected. However, tissue ascorbate stores fell significantly, by 20-30%. The lack of effects on antibody responses and NT are discussed n terms of the acute nature of the stressor used in this model, as opposed to the more chronic stressors that have occurred in the human model.

Haemolysis associated with continuous venovenous renal replacement circuits.

Extracorporeal circuits can cause haemolysis resulting in an increase in plasma-free haemoglobin (PFHb). High pressures and clots within the circuit have been identified as factors increasing the likelihood of haemolysis. Continuous venovenous haemodiafiltration (CVVHD) is associated with high circuit pressures as the pump-driven circuit clots over a period of time. PFHb was measured during CVVHD to determine if circuit life, maximum circuit pressure or the clotting of the haemofilter was associated with evidence of haemolysis. Circuit life up to 50 hours, circuit pressures or haemofilter clotting had no significant effect on PFHb. There was a small rise in PFHb in the circuits lasting beyond 50 hours. CVVHD circuits can be run up to 50 hours without concern for haemolysis.

Do-it-yourself femoropopliteal bypass.

A 74-year-old male claudicant had undergone operative repair of his bilateral varicose veins 22 years earlier. His records confirmed that on the right side he had only had a saphenofemoral disconnection. Duplex scanning and angiography of his right leg demonstrated an occluded superficial femoral artery (SFA) and a network of channels between the proximal SFA stump and the long saphenous vein (LSV). Distal SFA reconstitution occurred through two distal arteriovenous fistulas. We believe that this is the first case of a spontaneous femorodistal bypass graft secondary to neovascularisation recorded in the literature.

Unusual pulmonary complication of ulcerative colitis with a rapid response to corticosteroids: case report.

Extraintestinal features of ulcerative colitis are well recognised. Pulmonary complications include pulmonary vasculitis, fibrosing alveolitis, asthma, and chronic bronchial suppuration. A case is described of a patient with longstanding quiescent ulcerative colitis who developed a life threatening pulmonary complication, which is extremely sensitive to corticosteroid treatment.

Increased calcium absorption in nephrolithiasis explained by uptake studies in ileal brush border membrane vesicles.

We previously showed that recurrent calcium renal stone formers have enhanced urinary excretions of calcium and oxalate resulting from malabsorption of citrate. In the present investigation, the mechanism of the citrate-induced increased calcium uptake was studied using guinea pig ileal brush border membrane vesicles. In this model, calcium is absorbed in a concentration dependent, single mechanism uptake with a Km of 275 +/- 30 umol/liter (SD) and a Vmax of 4.0 +/- 0.5 nmol/min.mg protein. Under conditions of maximal calcium uptake, both citrate and phosphate inhibited calcium absorption into brush border membrane vesicles (BBMVs). In contrast, when phosphate and citrate were added together, calcium absorption normalized. Citrate inhibition of calcium absorption appeared to be due to free citrate ions, and phosphate ions overcame this inhibition. Phosphate inhibition was mostly due to decreased concentrations of ionized calcium and partly to precipitation of insoluble calcium phosphate. These studies confirm that the effects of citrate in humans in enhancing calcium absorption occur in the lumen of the gut and are not related to further biochemical conversions of citrate by the gut cells, to effects of citrate on calcium-related hormones, or to the renal handling of calcium. Also, the effects of citrate on increasing calcium absorption should be increased or attenuated in patients who malabsorb citrate, and this explains the increased urinary calcium and oxalate excretions reported for recurrent calcium stone formers.

The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.

Estimation of plasma and urinary hemoglobin by a rate spectrophotometric method.

A method is described for estimating plasma and urinary hemoglobin concentrations as low as 3 mg/L. The assay measures at 528 nm the rate of peroxidation of chlorpromazine by hemoglobin and is not affected by ascorbate and bilirubin concentrations up to 500 mumol/L. Results by this method (mean +/- SD: 54.4 +/- 41.6 mg/L; n = 19) correlated well with those by a scanning spectrophotometric method (52.5 +/- 41.6 mg/L; r = 0.96) and a Coulter Instrument method (r = 0.99; Coulter method: 125 +/- 15 g/L; rate method: 122 +/- 15 g/L; n = 10, r = 0.99). The correlation for assays of 20 plasma samples by our method and a tetramethylbenzidine method was also good (r = 0.95) though the latter gave lower results (31.1 +/- 31.6 mg/L) than the chlorpromazine method (50.9 +/- 41.1 mg/L). The chlorpromazine rate method gave an intra- and interday CV of 7.9% and 9.7%, respectively, at a hemoglobin concentration of 31 mg/L.

Simple, sensitive measurement of carbon monoxide in plasma.

A simple, sensitive method for estimating carbon monoxide in plasma is described. In this method, the carbon monoxide in plasma is trapped with hemoglobin and subsequently estimated by dithionite reduction. The method has an intra- and interassay precision (CV) of 10.7% and 12.8%, respectively, at a concentration of 1.12 mg of carbon monoxide per liter and has a detection limit of 0.1 mg/L. The reference interval for carbon monoxide in plasma from 17 men and eight women ranged from 0.14 to 0.60 mg/L (mean 0.36 mg/L).

A semi-automated method for 5'-ectonucleotidase measurement in lymphocytes.

We describe a simple, non-radioactive, semi-automated method for measuring lymphocyte ecto-5'-nucleotidase activity in isolated cell homogenates. The method which uses inosine 5'-monophosphate (IMP) as a substrate was optimized and requires a total of 4 x 10(6) lymphocytes. The reference range obtained (38.7-180.0 nmol/h per mg protein; means = 106.6) agrees with other isotopic methods which use 14C-IMP. The simplicity, sensitivity (lower limit 10, upper limit 400 nmol/h per mL) and precision (at 114 nmol/h per mL, interday 4.2% s.d., n = 20; intraday 5.8%, n = 10) makes this method suitable for routine clinical laboratory use.

The value of investigation for genetic counselling in tuberous sclerosis.

Forty sets of parents and 24 sibs of patients with tuberous sclerosis were investigated by an extensive protocol, including clinical examination of skin, hair, and oral cavity, direct and indirect ophthalmoscopy, cranial CT scan, renal ultrasound, and a radiological skeletal survey. None of the clinical examinations provided evidence that any of the subjects was affected. Similarly, the cranial CT scan, renal ultrasound, and skeletal survey failed to identify any occult gene carriers. All of these investigations showed abnormalities in some parents but none was diagnostic. This study shows the difficulties in interpretation that these investigations may produce with consequent problems for genetic counselling. The study does not support the routine use of these tests. There are published reports where the diagnosis of tuberous sclerosis has been made in adults exclusively on a CT scan and an argument can be made for including this investigation. There is no indication for performing renal ultrasound nor skeletal x rays in parents who have normal clinical examinations.

Lymphocyte ectoenzyme activity compared in healthy persons and patients seropositive to or at high risk of HIV infection.

We measured two ectoenzymes, ecto-5'-nucleotidase (NT) and dipeptidyl peptidase IV (DP) in the peripheral blood lymphocytes of various groups of HIV-infected patients because of the previous implied relationship of these enzymes to immune function. NT expressed as mean nmol/h per mg protein (+/- s.d.) was significantly depressed in the HIV-seropositive asymptomatic (42 +/- 32; P less than 0.01) and AIDS groups (14 +/- 7; P less than 0.002) when compared with a healthy HIV-seronegative male population (83 +/- 27). The NT activities in asymptomatic HIV-seropositive and HIV-seronegative high risk groups (53 +/- 30) were not significantly different from one another but both groups had significantly higher enzyme activities than the AIDS group (P = 0.01 and less than 0.002, respectively). The seronegative high risk and normal healthy group had similar NT activities. DP activities expressed as mean nmol/h per mg protein (+/- s.d.) in both seropositive asymptomatic (0.188 +/- 0.038) and high risk seronegative (0.180 +/- 0.05) groups had higher enzyme activities than the healthy seronegative (0.117 +/- 0.015; P = 0.02 and 0.05, respectively) and AIDS group (0.096 +/- 0.036; P = 0.002 and 0.02, respectively). The healthy seronegative group had DP activities not significantly different to the AIDS groups. Similarly the high risk seronegative and healthy seropositive group had similar DP activities. These results taken together indicate that measurement of both DP and NT should be evaluated prospectively as a monitor of the clinical progression of HIV infection.