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Background and aim-The present study was undertaken to determine if detection of Ki-ras gene point mutations in bile specimens could diVerentiate between benign and malignant biliary strictures. Patients-Bile specimens were obtained from 117 patients exhibiting a stricture of the main bile duct, the nature of which was assessed by cholangiography, histology, and follow up. Methods-DNA from frozen bile specimens was extracted, amplified, and tested for codon 12 point mutations of Ki-ras gene using sequence specific oligonucleotide hybridisation and mutant allele specific amplification. Results-DNA amplification was successful in 110/117 bile specimens (94%). Detection of Ki-ras gene mutations in bile specimens was positive in 24.4% (22/90) of patients with malignant strictures, in 31.4% (22/70) when only primary malignant tumours were considered, and in 4% (1/25) of patients with benign strictures. Of the 49 patients with histological specimens obtained before surgery, the sensitivity of histology, Ki-ras mutation analysis, and combined methods was 59.2%, 28.6%, and 73.5% respectively. Conclusions-Our study showed that Ki-ras mutations may be detected in about one third of bile specimens from patients with primary tumours invading the main bile duct. Detection of such mutations appears to be specific and may help to diVerentiate between benign and malignant biliary strictures.

Delayed intradermal sensitivity to homologous white blood cells has been described in humans rejecting full thickness skin homografts (1). The reaction at the site of the challenge leukocyte was greatest at 18 to 24 hours against the cell suspensions obtained from the skin donor. It was noted, however, that lesser reactions were consistently elicited to similarly prepared and simultaneously injected leukocytes obtained from donors other than the sensitizing skin donor. There was no recipient response to injections of autologous leukocytes, homologous erythrocytes or homologous plasma. Biopsy sections taken at peak reaction times were similar to early tuberculin responses. It was postulated that the skin erythema and induration were a manifestation of an antigen-antibody reaction, in which antibodies developed against the skin homograft were capable of also reacting with shared antigen (s) within or upon the peripheral white blood cell. To explain the lack of specificity of the skin response, it was assumed that there is a distribution of common transplantation antigens in the human, as has been shown by Berrian and Jacobs in the mouse (2).The present experiment supports this supposition and suggests that transplantation immunity in the human is not as specific a phenomenon as has been previously proposed (3).

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A method was developed for the demonstration of intrarenal lymphatics by the retrograde injection of contrast medium directly into capsular or hilar lymphatic trunks. Utilizing this method in the dog, intrarenal lymphatics were found to be distributed primarily along arcuate blood vessels and in interlobular spaces with small branches closely associated with Bowman’s capsule. These lymphatic vessels were found to be continuous with both capsular and hilar lymphatic trunks. Data derived from a horse and a calf support the findings in dog concerning periglomerular lymphatics and the interlobular distribution respectively. Although this study does not preclude the existance of medullary lymphatics, we have never observed injected lymphatics in this area. On the basis of the lymphatic distribution found in this study, renal lymph is derived primarily from fluid formed in the periarterial spaces along with a component derived from the immediate vicinity of Bowman’s capsule.

The incidence of solitary toxic adenoma of the thyroid in a general surgical unit with an interest in thyroid disease has been reviewed over a 15-year period. Six hundred and thirty thyrotoxic cases were treated surgically, 35 (5.6 per cent) having a solitary toxic adenoma. Thyroid enlargement or toxicity had been present for more than 5 years in 7 patients (20.0 per cent). Cardiovascular complications were present in 6 cases (17.1 per cent). Thyroid lobectomy resulted in 30 (85.7 per cent) euthyroid and 5 (143.3 per cent) hypothyroid patients. One toxic adenoma contained a focus of carcinoma. The clinical features, diagnosis and management of solitary toxic adenoma, and the management of symptomatic nodules which are 'hot' but not biochemically toxic, are discussed.

A case of villous adenoma of the bladder associated with cystitis glandularis of intestinal type is described. Only three villous adenomas have been reported to date, of which two were also accompanied by cystitis glandularis. The lesion can be confused with polypoid hyperplasia in cystitis glandularis. Neutral mucins, acidic sulphomucins, and sialomucins were identified within the villous adenoma and adjacent areas of cystitis glandularis. It is suggested that the villous adenoma may form an intermediary stage in the development of some of the primary adenocarcinomas of the bladder arising in metaplastic intestinal mucosa. ( Clin Pathol 1993;46:450-452) Villous adenomas arising in the bladder are rare tumours but have been described as isolated cases,' or in association with cystitis glandularis.3 Some primary adenocarcino-

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