Nanostrain sensitivity in a wire torsion experiment.

The feasibility of a thin-wire torsion stress-strain experiment with nanostrain sensitivity is demonstrated. A gauge length of 50 m was made possible by using The Monument, London, thereby restoring it to its original purpose as a scientific instrument. A wire of 150 µm diameter was studied using the load-unload method, and data were recorded in the elastic regime and through the elastic-plastic transition. Analysis of this preliminary experiment suggested some necessary improvements to the equipment and methods. Progress towards definitive experiments is described together with difficulties still to be overcome.

Oral squamous cell carcinoma after allogeneic bone marrow transplantation for Fanconi anaemia.

We report a case of oral squamous cell carcinoma (SCC) originating in the buccal mucosa of an 18-year-old female patient with chronic graft-versus-host disease (GVHD) 9 years after HLA-identical sibling bone marrow transplantation (BMT) for Fanconi anaemia (FA). The case highlights the problems of malignant change in FA and also the increased risk of second malignancy after BMT. The literature is reviewed with regard to previous cases and the possible aetiology of tumour formation. A high index of suspicion to any epithelial lesion in FA is appropriate so that early diagnosis may lead to improved prognosis.

Spontaneous graft-versus-host disease following autologous peripheral blood progenitor cell transplantation in chronic myeloid leukaemia.

Myeloablation followed by haemopoietic reconstitution using autologous peripheral blood progenitor cells (PBPC) is applicable to some patients with CML, particularly where there is no allogeneic stem cell donor available, and interferon alpha has failed to achieve a significant cytogenetic response. Cells lacking the Philadelphia (Ph) chromosome can be collected at the early phase of myeloid recovery after intensive chemotherapy, and reconstitution after autografting can be associated with prolonged suppression of the Ph positive clone. It is possible that mechanisms other than this "in vivo purge' may contribute to disease control, for example an autologous graft-versus-leukaemia effect. We report two patients in whom significant autologous graft-versus-host disease (auto-GVHD) has occurred, which has not previously been described as a spontaneous event after PBPC autograft for CML. We postulate that mononuclear cells collected in an early phase of recovery after intense myelosuppression have the capacity to produce self-reactivity after autografting. These cells, which may include autoreactive T lymphocytes or antigen-presenting dendritic cells, might mediate a useful graft-versus-leukaemia effect.

Expression of chorionic gonadotrophin in human pituitary adenomas.

In addition to the classical anterior pituitary hormones, many human pituitary adenomas express hormone genes ectopically. Expression of glycoprotein hormone alpha-subunit and, less commonly, free luteinizing hormone beta (LH-beta) or follicle-stimulating hormone beta is characteristic of endocrinologically inactive adenomas, a subgroup thought to be derived predominantly from the gonadotroph line. Thyrotrophin beta expression in these tumours is unusual, and specific chorionic gonadotrophin beta (CG-beta) expression, identified using oligonucleotide probes that reliably distinguish LH-beta and CG-beta in situ, is not well described. Using in situ hybridization histochemistry with a CG-beta transcript-specific oligonucleotide probe and a non-specific LH/CG-beta oligonucleotide and riboprobe, we have demonstrated specific CG-beta expression in two of 35 random pituitary adenomas; LH-beta expression occurred in a further eight adenomas. Unlike prolactin, growth hormone and proopiomelanocortin, which are transcribed in the vast majority of cells in their respective hormone-positive tumour subtypes, the pattern of LH/CG-beta was typically a scattering of single or small clusters of hormone-positive cells in a predominantly LH/CG-beta-negative tumour. Finally, although bona fide CG-beta expression in human pituitary adenomas does occur, it is only at an incidence similar to that described for carcinomas of other tissues.

Autopsy findings in two cases of neonatal herpes simplex virus infection: detection of virus by immunohistochemistry, in situ hybridization and the polymerase chain reaction.

We describe the pathological findings in two fatal cases of neonatal infection with herpes simplex virus. One had an encephalitis caused by herpes simplex virus type 2 (HSV-2); the other had a disseminated infection with herpes simplex virus type 1 (HSV-1). Confirmation of the diagnosis was obtained by use of the polymerase chain reaction to amplify viral DNA from paraffin sections of autopsy tissues. By using primers which amplify fragments of the HSV-1 thymidine kinase gene and HSV-2 glycoprotein gene respectively it was possible to discriminate between infection with HSV-1 and HSV-2. In contrast, immunohistochemistry and in situ hybridization using commercially available reagents did not distinguish between HSV-1 and HSV-2 infection. However, immunohistochemistry and in situ hybridization are probably more reliable than the polymerase chain reaction for assessment of the distribution of virus in different tissues.

Vulvitis chronica plasmacellularis (Zoon's vulvitis).

Vulvitis chronica plasmacellularis (Zoon's vulvitis) is rare. We describe a case in whom all the typical features, as delineated by Zoon, are demonstrated.

Parvovirus infection of the human fetus and newborn.

Human parvovirus B19 is a recently recognized cause of hydrops fetalis. It is a small, single-stranded DNA virus, which preferentially infects late erythroid precursors and produces red blood cell (RBC) aplasia, fetal anemia, and cardiac failure. Infection is accompanied by characteristic intranuclear inclusions in fixed and circulating RBC precursors. These inclusions have been shown to contain virus particles by electron microscopy and in situ hybridization. Infection of the fetus, mother, and newborn infant can be diagnosed by serological and molecular methods selected to match the stage of the infection. Recent work has shown that parvovirus B19 can infect cells other than erythroid precursors, and that additional mechanisms such as myocarditis may contribute to hydrops fetalis in some cases. Infected fetuses are not always hydropic. Maternal infection results in increased abortion and stillbirth even in the absence of transplacental transmission, which occurs in approximately one third of infected mothers. The overall risk of fetal loss following maternal exposure is much less than previously thought, and may be less than 3% in the first 20 weeks of gestation or approximately 10% if the mother is actually infected. Although parvoviruses are teratogenic in animals, there is no evidence that B19 is a significant teratogen in man. The long-term outlook of survivors of intrauterine infection, including those successfully treated by intrauterine blood transfusion, appears to be good, but requires further study.

Sjögren's syndrome in systemic sclerosis. A clinical study of 26 patients.

Features of Sjögren's syndrome were sought in 26 patients with systemic sclerosis and in age- and sex-matched control subjects. The assessments included a structured history to establish symptoms of dry eyes and dry mouth. Schirmer's I and II tear tests. Rose Bengal staining with slit lamp microscopy of the eyes, measurement of basal and stimulatory salivary secretion. We measured sweat secretion rates from the skin. Salivary scintigraphy and skin biopsies were performed on the patients. Only one patient showed the complete picture of Sjögren's syndrome with both clinical and investigational evidence of lacrimal and salivary gland involvement. A further patient had an abnormal Schirmer's II test and xerostomia with reduced salivary secretion and an abnormal scan, but no ocular symptoms and no keratoconjunctivitis sicca on ophthalmological examination. Two patients had reduced salivary flow and a dry mouth. A number of patients and control subjects showed various individual symptoms and signs of lacrimal and salivary disorders. These features alone are not sufficient for the diagnosis of Sjögren's syndrome. There is a clear need to adopt strict criteria for diagnosing the condition. The association of Sjögren's syndrome with systemic sclerosis seems doubtful and if it does occur it is very much less common than previously suggested.

Intrauterine infection with human parvovirus B19: a light and electron microscopy study.

Recent reports have documented human parvovirus B19 infection in pregnancy, which may lead to spontaneous abortion, stillbirth or hydrops fetalis. Transplacental infection in a case of hydrops fetalis is demonstrated by light and electron microscopy observation of virus inclusions in all tissues examined. Parvovirus particles measuring approximately 20 nm were observed within the nuclei of erythropoietic cells. The parvovirus virions were observed most commonly as randomly distributed particles and rarely in crystalline assays. Thus definitive evidence of fetal infection confined to red cell precursors is documented.

Lichen sclerosus et atrophicus. A common and distinctive cause of phimosis in boys.

Lichen sclerosus et atrophicus, a disease said to be rare in boys, was found in 14 of 100 prepubertal boys undergoing elective circumcision for disease of the foreskin. The clinical features of the disease, in particular the acquired scarring phimosis of the tip of the prepuce, were distinctive. Extragenital involvement was not found. Scarring phimosis in boys must be considered to be one of the most common manifestations of lichen sclerosus et atrophicus.

The clinical assessment of duodenogastric reflux by scintigraphy and its relation to histological changes in gastric mucosa.

Fifty-seven patients undergoing routine or review gastroscopy had multiple gastric biopsies taken and assessed histologically for gastritis, metaplasia and dysplasia. Duodenogastric reflux was graded scintigraphically by BIDA Scanning. Patients with dysplastic changes in the gastric mucosa (n = 33) had a higher mean grade of reflux 2.1 +/- 0.21 (mean +/- SEM) than patients with no dysplasia (1.1 +/- 0.24: P less than 0.0025). Patients with metaplasia (n = 33) had an increased mean grade of reflux of 2.0 +/- 0.19 compared with patients without metaplasia (1.3 +/- 0.29: P less than 0.05), but there was no significant difference in degree of reflux between patients with and without gastritis. When the grade of reflux was plotted against increasing degrees of mucosal abnormalities, there appeared to be a positive correlation between duodenogastric reflux and severity of mucosal change.