Routine computerised tomographic scans of the thorax in surveillance of stage I testicular non-seminomatous germ-cell cancer--a necessary risk?

BACKGROUND: The standard management approach to stage I testicular non-seminomatous germ-cell tumours (NSGCT) in the UK is a surveillance programme with adjuvant bleomycin, etoposide, cisplatin (BEP) chemotherapy being offered to individuals with high risk disease. Conventionally, computed tomography (CT) scanning of the thorax has formed part of the surveillance programme. This paper evaluates the contribution of routine thoracic CT imaging in the management of this disease. PATIENTS AND METHODS: We retrospectively reviewed the case notes of 168 patients with stage I NSGCT referred to the Wessex Medical Oncology Unit over a period of 13 years (1986-1998). These patients entered onto a surveillance programme that included serial chest X-ray follow up rather than thoracic CT. RESULTS: Forty-two out of 168 patients (25%) evaluated suffered relapse during the follow up period. Eight of 42 patients (19%) relapsed with intrathoracic disease. Seven out of eight of these patients (87.5%) had at least one other indicator of disease recurrence (elevated serum marker, abnormal abdominal CT). One of 42 patients (2.4%) relapsed with isolated intrathoracic disease with no other indicator of relapse. All patients with intrathoracic relapse had evidence of disease on chest X-ray. Of the 42 relapsing patients, 93% could be categorised as having good prognosis metastatic disease. Seven per cent relapsed with intermediate or poor prognostic disease; relapse in these patients would not have been detected earlier with the inclusion of routine thoracic CT. Only one patient has died giving a cure rate of 98% for relapsing patients. CONCLUSIONS: The elimination of chest CT did not compromise outcome but significantly reduced radiation exposure thereby minimising the risk of radiation-induced secondary malignancy. Continued review of surveillance programmes is essential if we are to optimise management of this disease.

A novel approach to the design of inhibitors of human secreted phospholipase A2 based on native peptide inhibition.

Human Type IIA secreted phospholipase A(2) (sPLA(2)-IIA) is an important modulator of cytokine-dependent inflammatory responses and a member of a growing superfamily of structurally related phospholipases. We have previously shown that sPLA(2)-IIA is inhibited by a pentapeptide sequence comprising residues 70-74 of the native sPLA(2)-IIA protein and that peptides derived from the equivalent region of different sPLA(2)-IIA species specifically inhibit the enzyme from which they are derived. We have now used an analogue screen of the human pentapeptide (70)FLSYK(74) in which side-chain residues were substituted, together with molecular docking approaches that modeled low-energy conformations of (70)FLSYK(74) bound to human sPLA(2)-IIA, to generate inhibitors with improved potency. Importantly, the modeling studies showed a close association between the NH(2) and COOH termini of the peptide, predicting significant enhancement of the potency of inhibition by cyclization. Cyclic compounds were synthesized and indeed showed 5-50-fold increased potency over the linear peptide in an Escherichia coli membrane assay. Furthermore, the potency of inhibition correlated with steady-state binding of the cyclic peptides to sPLA(2)-IIA as determined by surface plasmon resonance studies. Two potential peptide interaction sites were identified on sPLA(2)-IIA from the modeling studies, one in the NH(2)-terminal helix and the other in the beta-wing region, and in vitro association assays support the potential for interaction of the peptides with these sites. The inhibitors were effective at nanomolar concentrations in blocking sPLA(2)-IIA-mediated amplification of cytokine-induced prostaglandin synthesis in human rheumatoid synoviocytes in culture. These studies provide an example where native peptide sequences can be used for the development of potent and selective inhibitors of enzyme function.

Haemobilia.

BACKGROUND: This review aims to establish whether increased use of invasive procedures and the trend toward conservative management of major trauma has resulted in an increased incidence of haemobilia. METHOD: A Medline (http://igm.nlm.nih.gov/)-based search of the English language literature from January 1996 to December 1999 inclusive was performed using the keywords haemobilia, hemobilia, haematobilia and hematobilia. The presentation, aetiology, investigation, management and outcome of 222 cases were reviewed. RESULTS: Two-thirds of cases were iatrogenic while accidental trauma accounted for 5 per cent. Haemobilia may be major, constituting life-threatening haemorrhage, or minor; it may present many weeks after the initial injury. Diagnosis is most commonly confirmed by angiography. Management is aimed at stopping bleeding and relieving biliary obstruction; 43 per cent of cases were managed conservatively and 36 per cent were managed by transarterial embolization (TAE). Surgery was indicated when laparotomy was performed for other reasons and for failed TAE. The mortality rate was 5 per cent. CONCLUSIONS: Although the incidence of iatrogenic haemobilia has risen considerably, the bleeding is often minor and can be managed conservatively. When more urgent intervention is required, TAE is usually the treatment of choice. There is no evidence that the conservative management of accidental liver trauma increases the risk of haemobilia.

Four-phase study of computer-assisted and slide-tape methods of stimulating clinical endodontic problems.

1. Computer-assisted instruction of stimulated clinical endodontic problems is superior to a slide-tape presentation for test selection but not for diagnosis and treatment planning. 2. The lack of a difference in diagnosis is likely due to the already superior performance of students in diagnosis at the University of Kentucky without computer assistance. A study with students of less background might reveal a difference in presentation methods. 3. Students with high GPSs score higher on a written test of endodontic clinical judgment. 4. Reliable results on the effects of a human tutor's supplementing machine instruction were not obtained. 5. Students felt that the problems presented in this study were useful in preparing for clinical treatment of patients. 6. After some exposure to machine methods of instruction, students divided into three sizable groups, one preferring a human teacher, another preferring a machine, and the third having no preference. The decision to use only machine or human instruction cannot then be made from student attitudes. 7. Students liked the active participation and immediate responses of the computer but not the time necessary to complete the problems. 8. Students liked the self-pacing, speed, and convenience of the slide-tape method but not the incompleteness of the problems presented by this method. 9. It appears that there is some justification from this study for offering both slide-tape and computer-assisted presentations to students.