p53 and p21waf-1 expression correlates with apoptosis or cell survival in poorly differentiated, but not well-differentiated, retinoblastomas.

In human retinoblastomas, rare genetic mutations of the retinoblastoma gene cause massive cell proliferation, altered differentiation, and tumor formation; but paradoxically, this is accompanied by extensive apoptotic cell loss. We quantified the immunohistochemical distribution of p53, its downstream effector p21 (WAF-1), and apoptotic cells in 50 human retinoblastomas, within three concentric zones of sleeves of tumor cells surrounding blood vessels. In poorly differentiated retinoblastomas, both p53 expression and apoptosis increase toward the outer zone of tumor sleeves, whereas p21 expression occurs primarily within the inner zone. This staining pattern of p53 expression is reversed in well-differentiated tumors, whereas p21 staining and apoptotic cell distributions are unchanged. We detected no p53 mutations in four retinoblastomas and two retinoblastoma cell lines. We postulate that oxygen and cell "survival/growth factors" delivered via blood vessels protect retinoblastoma cells from apoptosis. In poorly differentiated tumors, apoptosis is spatially associated with increased p53 expression and may be p53 mediated, but in well-differentiated tumors, apoptosis does not colocalize with p53 and may be p53 independent. In retinoblastomas, p21 is involved not in cell death by apoptosis but in cell survival. Thus, p53 varies its expression (and by implication its function) with altered differentiation in retinoblastomas.

In vivo measurements of indwelling tracheo-oesophageal prostheses in alaryngeal speech.

Over the last 5 years, detailed air pressure, flow and voice measurements have been made on indwelling tracheo-oesophageal speaking valves whilst inserted in patients, using specially designed apparatus. This study was set up to investigate the relationship between speech and in vivo parameters. In vivo pressure measurements were generally lower for Groningen low resistance than Groningen high resistance, while flow and voice measurements were higher. A plot of opening pressure against pressure at maximum flow for all valves suggested a straight line relationship. A graph of maximum voice against composite parameter score for all valves showed a cluster of points between the composite score of 0-15. The advances in knowledge about these valves should be of use in the design of improved valves.

Speech assessment of patients using three types of indwelling tracheo-oesophageal voice prostheses.

A multidisciplinary prospective study compared speech acceptability between three types of indwelling tracheo-oesophageal voice prostheses. Twenty male laryngectomees took part over five years, using 42 prostheses. Speech was assessed on a discrete scale by trained and untrained personnel. The majority scored in the mid-range for each assessor. The kappa coefficient was used to test similarity between assessors, and for all pairings agreement was significant (p < 0.05). The speech and language therapist tended to give higher scores and the patient lower. A relationship was found between patients' ages categorized by decade and the surgeon's score alone. This relationship held for Groningen high resistance and Provox prostheses individually too (p < 0.05). The untrained assessed similarly to the professionals--humans are all voice listeners. The analysis suggests surgeons find tracheo-oesophageal speech in older patients better than in younger ones; or make more allowances for the elderly. There was a trend for Provox prostheses to produce the best scores.

An investigation into the incidence of auto-immune disorders in patients with localized morphoea.

Patients with localized morphoea have an increased incidence of auto-immune disorders, but this is not related to the age of onset, duration of disease nor the site or number of lesions. The patients have an increased incidence of tissue antibodies and these are more common when more than one lesion is present. The relatives of the patients have also been found to have an increased incidence of auto-immune disorders. These findings suggest an immunological basis for the disease and indicate that the patients should be investigated and followed up to detect the evidence of other auto-immune disorders.

Does control affect growth in diabetes mellitus?

Factors affecting the growth of 67 diabetic children were analysed retrospectively. The effects of age, sex, three year average glycosylated haemoglobin (HbA1) levels, time since diagnosis and age at diagnosis were assessed on the change in the child's height standard deviation score (SDS) over three years, as well as the change in height SDS from diagnosis. No correlation between these factors was noted over a three year period; however, there was a strong correlation (p less than 0.001) in the change in height SDS from diagnosis with the age of the child and time from diagnosis. Multiple regression analysis revealed that the younger the child at original diagnosis, the less the height SDS loss, and also that in younger children the age of the child and not the time from diagnosis was the more important variable in deciding the loss in height SDS. No correlation existed between HbA1 levels and either the short or long term growth of patients in this study.

Final stature in brain tumours other than craniopharyngioma: effect of growth hormone.

The final growth pattern of 27 children who developed growth hormone deficiency after treatment of an intracranial tumour other than craniopharyngioma was assessed retrospectively. No patient achieved his or her genetic potential, though 12 attained an adult height above the the third centile for the population. All patients showed a tendency to a eunuchoid body build irrespective of whether puberty was spontaneous or not.

Non-Hodgkin's lymphoma in Sheffield 1971-1980.

Data from a study of 342 patients with histologically proven non-Hodgkin's lymphoma treated in Sheffield between 1970-1979 is presented. The Working Formulation for Clinical Usage (National Cancer Institute, 1982) has been applied to histology reviews. The overall 5 year survival was 34.2%. Analysis of data by two factor contingency table analysis of possible prognostic indices showed the favourable effects of low grade histology, localized extranodal staging, asymptomatic (A) status, complete response to initial therapy, high haemoglobin and normal ESR. Unfavourable markers were stage IV disease, histology other than low grade, older age, low haemoglobin and elevated ESR. One hundred and ten cases initially referred to our centre as non-Hodgkin's lymphoma were not histologically acceptable as such, one third of these showed reactive hyperplasia only. A broad spectrum of extra nodal lymphoma was seen in the series (78 patients, 23%); the commonest sites being Waldeyer's ring, gastrointestinal tract, thyroid and skin. Necropsy (50 patients) confirmed that infection, usually bronchopneumonia, in association with persistent lymphoma was the commonest cause of death.

Immunity in Hodgkin's disease: status after 5 years' remission.

Immunological indices have been reassessed in 27 patients in remission from Hodgkin's disease for 5 years after treatment and the findings correlated with initial treatment and splenectomy status. Neutrophil counts were lower and lymphocyte and monocyte counts higher at 5 years' remission than at presentation; the increases in lymphocyte count were mainly a feature of the splenectomized patients. Neutrophil function (nitro-blue tetrazolium) was unchanged in remission but cellular immunity (leucocyte migration inhibition and lymphocyte transformation) was depressed at 5 years and progressive falls in serum immunoglobulins were noted. Low values of IgG and IgM were particularly found in patients who had splenectomy and chemotherapy; there was however no excess of infections in this small group.

Lymphopenia: a bad prognostic factor in Hodgkin's disease.

Pretreatment peripheral blood lymphocyte counts have been recorded in 181 consecutive untreated patients with histologically proven Hodgkin's disease and the patients followed prospectively to determine the relationship of lymphopenia to survival. Lymphocyte counts at presentation did not correspond with histology type but were lower in stage 4 disease. Survival in the 77 patients with lymphocyte counts of less than 1.5 X 10(9)/l was 49.7% which was significantly worse (P less than 0.0001) than the 74.2% survival of those with 'normal' counts. This difference was maintained even after adjustment for other acknowledged prognostic variables including sex, age, stage, symptom status, histology type, and response to treatment. The study provides evidence that the lymphocyte count can be used as a meaningful marker in the clinical staging of Hodgkin's disease.

An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and atrophicus.

Patients with lichen sclerosus and atrophicus have an increased incidence of organ specific antibodies, and these patients and their relatives have a significantly higher incidence of associated autoimmune diseases than a control population. The incidence of other auto-immune diseases in patients with lichen sclerosus is highest when the onset is between the ages of 41 and 60 years, but is not related to the duration or site of the lesions. These findings suggest an immunological basis for the disease and indicate that the patients should be investigated and followed up to detect the existence of other auto-immune disorders.

Follow-up studies on the immune status of patients with Hodgkin's disease after splenectomy and treatment, in relapse and remission.

Sixty-two patients with Hodgkin's disease have been followed for one year from the start of treatment. Immunological assessments were repeated after intensive treatment, in patients relapsing and in those in remission at one year. In patients achieving remission, overall cellular immunity, after deteriorating with therapy, particularly cytotoxic chemotherapy, returned to pre-treatment levels in remission when there was little evidence of cellular immune disturbance. Serum IgG and IgM levels fell with intensive chemotherapy in splenectomized patients. IgA and IgM levels were lower (irrespective of splenectomy or therapy status) in remission than at presentation or after treatment. Relapse or non-response was usually associated with deteriorating cellular immunity. Herpes zoster/varicella and candida infections (seen in 6 patients) were preceded by, or associated with, deterioration of cellular immunity.