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During the first 2 years (July 1989 to July 1991) of the Avon Breast Screening Service, fine-wire localization biopsy was indicated in 213 impalpable breast lesions. A total of 144 lesions were benign and 69 malignant. Only four of 213 lesions (1.9 per cent) were not excised at the first localization. Factors influencing reoperation in the 69 patients with malignant impalpable lesions were examined. There was a significant association (P < 0.001) between parenchymal disturbances on mammography and invasive carcinoma, and between non-invasive carcinoma and microcalcification (P < 0.001). In 31 patients the localization biopsy was the only surgical procedure. Thirty-eight patients required further surgery: 12 underwent further local excision and 26 mastectomy. Reoperation was more frequent in patients with calcification than in those with parenchymal disturbance (P < 0.001). The most frequent indications for mastectomy were inadequate excision of widespread comedo ductal carcinoma in situ or invasive ductal carcinoma combined with extensive ductal carcinoma in situ. Fine-wire localization biopsy was a combined therapeutic and diagnostic procedure in 31 of 69 women with impalpable screen-detected lesions. The majority of patients required further surgery because radiological abnormalities underestimated the extent of disease.

Epidermal growth factor (EGF) receptor status is a useful prognostic indicator in women with breast cancer. Lack of standardization and correlation of methodology for the detection of EGF receptor has hampered its further evaluation. EGF receptor status was ascertained by immunohistochemistry and radioligand assay in 120 breast cancers. Of 52 tumours negative for EGF receptor on radioligand assay, 47 were negative on immunohistochemistry and, of 68 tumours positive for the receptor on assay, 52 were positive on immunohistochemistry. If the more widely evaluated radioligand assay is assumed to be the ‘gold standard’, immunohistochemistry has a sensitivity of 81 per cent and a specificity of 91 per cent.

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction–single-strand conformational polymorphism (PCR—SSCP) analysis, mutations in p53 exons 5–8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR—SSCP analysis were more common in grade III tumours (P = 0·015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.

Epidermal growth factor receptor (EGFR) is a sensitive prognostic indicator in women with breast cancer. A new technique for the detection of EGFR on breast cancer imprints is described and evaluated in relation to immunohistochemistry on frozen sections. The standard streptavidin-biotin method using the R1 antibody on frozen sections was modified for use on tumour imprints. In the first group (group 1 imprints) 43 tumours were assessed by frozen section and imprint staining. The group 1 imprint method had a sensitivity of 50% and a specificity of 89% compared with the frozen sections. Further modifications were made for the following 32 tumours (group 2) and this method had a much improved sensitivity of 94% while specificity was preserved. This method is simple and could be performed in any hospital histopathology department.

A total of 393 nipple discharge or scrape smears from 360 women were examined cytologically over a 12-year period. Twenty-nine breast cancers (8 per cent) have been histologically confirmed in this group, of which 16 had malignant smear cytology (sensitivity 55 per cent). Nine patients with breast cancer and positive cytology had impalpable tumours. Two of these cancers were not detected by any other investigation. Thirteen patients with nipple discharge had false-negative cytology, but there were no false-positive results (specificity 100 per cent). All patients with expressible or spontaneous nipple discharges and those with skin changes at the nipple should undergo examination of cytological smears.

After arterial reconstruction, patients have traditionally been followed up in clinic in the long term. We have pursued a policy of limited clinic follow-up, with an 'open access' service for suspected graft failure (and latterly duplex scanning surveillance for vein grafts). This policy was assessed by measurement of the success of self-referral, graft patency and patient satisfaction after operation for lower limb ischaemia in 173 patients. At median follow-up of 50 months, 61 (35%) patients had died and 45 (25%) had required amputation. Of those with salvaged limbs and available for follow-up, 55 (86%) patients reported continuing symptomatic improvement with a graft patency rate of 80%. During the review period, 27 (42%) patients had presented themselves on suspicion of graft occlusion and 14 (52%) of these had required surgical intervention. Of the patients, 45 (70%) found a single postoperative clinic visit helpful, and the majority thought that further visits would not have been helpful to them. Limited clinic appointments seem especially desirable for elderly patients for whom journeys are an imposition, as well as reducing travel costs, and giving surgeons more time to deal with new referrals. These results suggest that properly educated patients present themselves when signs of graft occlusion occur, and there is little to be gained by regular long-term clinic follow-up in vascular surgical practice.

Medullary thyroid carcinoma accounts for 5–10 per cent of thyroid malignancies and occurs sporadically, and in three familial settings with autosomal dominant inheritance. Calcitonin, a 32 amino acid 3.5-kDa protein, is a biochemical marker of the tumour. Serum levels correlate with disease burden. Treatment initiated by screening allows disease removal at a premalignant phase: C cell hyperplasia. Genetic linkage studies locate the multiple endocrine neoplasia type 2A gene near the centromere of chromosome 10. Flanking genetic markers may allow polymorphic probes to examine DNA from a once-only blood sample to identify affected individuals. At what age thyroidectomy should be carried out in these patients is unclear.

The purpose of this study was to validate a field test of cardiorespiratory fitness for men with mental retardation. The subjects were 19 healthy young men (26 +/- 6 yr) with moderate mental retardation (IQ = 48 +/- 11). Each subject underwent a maximal treadmill test after a three-phase familiarization process. Each subject also completed a 1-mile walk test twice (Rockport Fitness Walking Test = RFWT). The correlation coefficients between peak VO2 on the treadmill and the two 1-mile walks varied from 0.78 to 0.83. When weight, height, age, heart rates of 1-mile walks, and their combinations were held constant, the correlations were strengthened. Using multiple correlation analysis the best equation for predicting peak VO2 was: Peak VO2 = 101.92 - 2.356(mile-1 time) - 0.42(weight). This model accounted for 85% of total variance. The standard error of estimate was 4.06 ml.kg-1.min-1. The test-retest reliability of the RFWT for the 19 subjects used in this study was very high (R = 0.97). This finding suggests that the RFWT is a valid and reliable field test for this population and appears to be a valid indicator of cardiorespiratory fitness for these men with mental retardation.

On Two Deflationary Truth Theories.- Some Reflections On The Prosentential Theory of Truth.- Paradox and Reference.- Two Theorems concerning Stability.- The Complexity of Decision Procedures in Relevance Logic.- Relevant Predication 3: Essential Properties.- The Dog: Relevance and Rationality.- Consistency and Logical Consequence.- On What Cannot Be.- Durations: Temporal Intervals with Gaps and Undetermined Edges.- Categorical Semantics.- The Myth of the Intuitionistic "Or".- What Mathematical Truth Need Not Be.- A Tour of the Multivariate Lambda Calculus.- Choice Trees.- The Extensional but Hyper-Intensional Calculus C? with Orderless Constants and Variables.- A Skeptical Theory of Mixed Inheritance.- The Logic of Mitchill v. Lath.- What are Absolute Probabilities a Function of?.- How Prediction Enhances Confirmation.- Figures in a Probability Landscape.- Nuel Belnap: Curriculum Vitae.- Nuel Belnap: Doctoral Students.- Nuel Belnap: Publications.- Index of Names.- Index of Subjects.

In the Preface to his Two Treatises of Government in 1689 Locke expressed the hope that the arguments of his book would besufficient to establish the Throne of our Great Restorer, Our present King William; to make good his Title, in the Consent of the People, which being the only one of all lawful Governments, he has more fully and clearly than any Prince in Christendom: And to justifie to the World, the People of England, whose love of their Just and Natural Rights, with their Resolution to preserve them, saved the Nation when it was on the very brink of Slavery and Ruin.(1) He went on to express his confidence that the King and Body of the Nation had between them by this time so thoroughly confuted the divine right hypothesis of Sir Robert Filmer that no future writer would be likely to have the effrontery to advocate slavery and threaten the common safety again. It was an eminently partisan summary of English political experience over the preceding decade. But there can be no doubt of its sincerity and accuracy as an expression of Locke’s own political attitudes on the February afternoon that he sailed from Holland in the flotilla of Princess Mary, to land in England the day before Mary and her consort announced their joint acceptance of the English throne (2).

Recoarctation is a problem in some patients after subclavian flap aortoplasty. To investigate the reason for recoarctation, we reviewed the records of 26 infants who underwent subclavian flap repair for symptomatic coarctation of the aorta at less than 3 months of age between June, 1979, and December, 1983. Age at repair ranged from 2 to 65 days (median 16 days) and weight from 2.1 to 4.9 kg (median 3.4 kg). In 14 patients the coarctation was associated with significant intracardiac defects (complex in six). There were two intraoperative deaths and one early death (surgical mortality 12%). The survivors were followed from 6 weeks to 66 months (median 12 months). Five survivors (22%), all operated on at less than 14 days of age, developed severe recoarctation 6 weeks to 6 months (median 5 months) after repair. The obstruction appeared to be due to lumen obliteration by shelf-life posterior wall tissue. Morphometric analysis of preoperative angiograms showed no correlation between recoarctation and distance between the left subclavian artery and the site of coarctation, length of the isthmus, diameter of the isthmus, combined cross-sectional area of the left subclavian artery and isthmus, or the ratio of the combined cross-sectional area of the left subclavian artery and isthmus to the cross-sectional area of the descending thoracic aorta. Recoarctation did not correlate with weight at operation, but it correlated significantly with age at aortoplasty (p = 0.02). The results suggest that intrinsic abnormalities of the periductal aortic wall are responsible for recoarctation after subclavian flap aortoplasty. Particular attention to this abnormal tissue at repair may prevent early recurrence in young infants.

Four cases of palliative Mustard or Senning repair for transposition of the great arteries (TGA) with ventricular septal defect (VSD), hypoplastic right ventricle, and superior-inferior ventricular configuration are presented. The palliative Mustard procedure-a Mustard repair without VSD closure-is usually reserved for patients with pulmonary vascular obstructive disease (PVOD). In such cases, VSD closure would result in left ventricular failure. Each of our four patients had normal or only slightly elevated pulmonary resistance (1.0 to 5.2 Wood units). However, in each case a hypoplastic right ventricle precluded VSD closure. All four patients had transposition-like hemodynamics with unfavorable streaming to the great arteries, despite the fact that two patients had a levo arterial configuration. In each case, the ventricular relationship included a hypoplastic, superior right ventricle with a horizontal ventricular septum-the so-called "upstairs-downstairs" or "superior-inferior" heart. All patients had previous balloon atrial septostomy or open septectomy to improve atrial mixing. Two patients had previous pulmonary artery banding because of increased pulmonary flow. All four patients remain survivors of the palliative Mustard or Senning repair, which was performed at 10 months, 5 1/2, 12, and 16 years. In each case, there was a marked improvement of symptomatology with a decrease of hemoglobin (mean 21.1 gm/dl preoperatively to 15.3 gm/dl postoperatively) and an increase of arterial oxygen saturation (mean 78 vol % preoperatively to 93 vol % postoperatively). This is the first palliative Mustard or Senning repairs in patients with TGA, VSD, and hypoplastic right ventricle without PVOD. The procedure produces gratifying palliation for these patients.

Aortico--left ventricular tunnel (ALVT) is a rare anomaly, only 21 such cases having appeared in the literature. This report describes a case of ALVT in which there were features characteristics of sinus of Valsalva aneurysm (SVA). Details of the operative repair are discussed.

A case is presented of failure of a Hancock porcine xenograft mitral prosthesis secondary to disruption of the prosthetic leaflets. Clinical, hemodynamic, and echocardiographic evidence of prosthetic dysfunction has been correlated with operative, pathological, and ultrastructural findings. Other instances of dysfunction of this prosthesis have been reviewed. Echocardiography should be routinely employed when the diagnosis of xenograft dysfunction is entertained.