Incidence and thickness of primary tumours and survival of patients with cutaneous malignant melanoma in relation to socioeconomic status

OBJECTIVE: To study incidence of and survival from cutaneous malignant melanoma in relation to socioeconomic status. DESIGN: Application of Carstairs deprivation score to all malignant melanoma patients diagnosed in a geographically defined area over a 15 year period. SETTING: West of Scotland (area population 2,716,900). SUBJECTS: 3142 patients first diagnosed with malignant melanoma in the period 1979-93. INTERVENTIONS: Surgical excision of primary malignant melanoma with additional treatment as appropriate and follow up until December 1994. MAIN OUTCOME MEASURES: Malignant melanoma incidence, primary tumour thickness and five year survival by socioeconomic status. RESULTS: From 1979 to 1993, the age standardised incidence rate for cutaneous malignant melanoma was 9.1/100,000 for the most affluent men and 2.4/100,000 for the least affluent men and 16.1/100,000 and 5.0/100,000 respectively for most and least affluent women (P < 0.001 for trend in both). The incidence increased steadily over time in both sexes in all socioeconomic groups. Good prognosis tumours ( < 1.5 mm thick) were most common in the most affluent men and women, and over the study period the proportion of such tumours increased most in the intermediate affluence group (both sexes) and in the least affluent women. Five year disease free survival from melanoma for the sexes combined was 81% for most affluent, 77% for intermediate, and 73% for least affluent groups. Even after adjustment for known prognostic factors of tumour thickness, ulceration, age, and body site of primary melanoma, the more affluent the group, the better the survival. CONCLUSION: Although the incidence of cutaneous malignant melanoma is higher among more affluent people, the prognosis is better in this group than for less affluent individuals. Early diagnosis campaigns should be targeted particularly to less affluent men and primary prevention campaigns should emphasise the greater risk in more affluent women.     

Angiography in giant-cell tumours of bone

The angiographic appearance of 9 cases of genuine giant-cell tumour of bone, 6 cases of aneurysmal bone cyst and one case of non-ossifying fibroma is described. Differential diagnosis would appear to be possible to a certain extent. The non-ossifying fibroma was poorly vascularized. The genuine giant-cell tumours were hypervascularized as well as some of the aneurysmal bone cysts making a differential diagnosis in these cases impossible. On the other hand, a poorly vascularized tumour devoid of soft tissue component and arteriovenous fistulas is probably an aneurysmal bone cyst. A hypervascular soft tissue component is of great prognostic value in cases of geniune giant-cell tumour.     

Frequency of bilateral tumours and primary retroperitoneal localization in tumours of the testicles

Report on 4 patients with bilateral testicular tumours (out of a total number of 181 cases) and the problems arising with a second course of irradiation. The question of histogenesis and therapeutic course in 4 patients with a primary retroperitoneal tumour localization are discussed in the second part.     

Measurement of total and local bone morphogenetic protein concentration in bone tumours

OBJECTIVE: To evaluate the relative effectiveness of two self-help smoking interventions as adjuncts to a self-help manual and telephone support service (hotline) for older smokers. DESIGN: Subjects were stratified on baseline variables and randomised to one of two treatment conditions in a methods development study. SUBJECTS: 177 community-dwelling smokers aged 60 years and older. INTERVENTIONS: All subjects received a self-help manual and access to a smokers' telephone hotline. Subjects also received either mailings (Letters condition) or counselling telephone calls (Proactive condition) at four and eight weeks after enrollment. MAIN OUTCOME MEASURES: Use of the hotline and prevalence of abstinence lasting at least 48 hours (verified by a "significant other") were assessed at three and six months for the full sample. Seven-day abstinence was calculated for comparison with previous research. A subsample of 91 subjects was followed up at 12 months. RESULTS: Overall abstinence rates for the two conditions were in the range of typical self-help interventions. Men were more likely to be abstinent than women at follow up at three and six months. A significant gender x treatment interaction was found, with abstinence rates higher for men in the Letters condition, and women in the Proactive condition. Hotline use was high, with nearly half of subjects calling by 12 months. CONCLUSION: Both interventions appear promising for older smokers, but may be differentially effective for men and women. Older smokers will use a hotline; whether Letters and Proactive interventions can improve on manual and hotline effectiveness rates alone is being tested in a subsequent controlled trial.     

Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and the bcl-2 oncogene in primary testicular germ cell tumours

The role of p53 in testicular germ cell tumours is still contradictory based on the finding of immunohistochemical overexpression at the protein level, but lack of mutations at the DNA level. In addition, p53 wild-type activity has been demonstrated in cell culture experiments. Overexpression of the proto-oncogene bcl-2 might block p53-induced apoptosis and might inhibit p53 functional activity. To clarify the apparent paradox with respect to p53 overexpression and lack of mutations, an immunohistochemical and mutational analysis of p53 and bcl-2 in TGCT was performed. Ten normal testes, 52 CIS and 151 clinical stage I nonseminomatous GCTs were included in our study. A commercially available anti-p53 polyclonal rabbit antibody and an anti-bcl-2-mouse monoclonal antibody were used to stain the 5pm sections. Staining was assessed by counting at least 500 cells from the area of the most intense staining in each tumour cell type, and this was scored semiquantitatively for intensity of staining on a 4 point scale. In addition, 30 primary GCTs were included in the mutational analysis: areas with p53 overexpression were identified and microdissected prior to DNA extraction. p53 exons 5-8 were amplified by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis. Templates demonstrating band shifts on SSCP were subjected to direct DNA sequence analysis. None of the normal testes, 32/52 (62%) CIS, and 142/151 (94%) germ cell tumours exhibited p53 overexpression. p53 expression was significantly lower in mature teratomas (0.8 +/- 0.2) than in other germ cell tumour components (2.8 +/- 1.2, p > 0.001). PCR-SSCP did not reveal any missense mutations or deletions for the p53 gene. Bcl-2 protein expression was observed in none of the normal testes, in none of the CIS, and in 14/151 (9.3%) germ cell tumours. 13/14 germ cell tumours demonstrated bcl-2 expression only in the glandular and stromal elements of their teratomatous components whereas all other components were negative for bcl-2. Our results--p53 overexpression, lack of p53 mutations, undetectable bcl-2--are consistent with recent in vitro studies. High susceptibility of testicular cancer to drug-induced apoptosis appears to be the result of wild-type p53 and lack of bcl-2. Radiation and chemotherapeutic insensitivity of mature teratomas might be the result of bcl-2 overexpression and lack of p53 overexpression. Therefore, chemoresistance to DNA damaging agents might be reflected by the expression of p53 and bcl-2 and it might be useful to evaluate p53 and bcl-2 in primary tumours and metastatic lesions in order to identify patients early with primary or secondary chemoresistance.     

p53 expression, DNA content and cell proliferation in primary and synchronous metastatic lesions from ovarian surface epithelial-stromal tumours

The aim of this study was to investigate biological heterogeneity between primary and metastatic ovarian cancer lesions from individual patients as a means of elucidating steps in clinical progression. Cancer tissue from 61 untreated patients with ovarian surface epithelial-stromal tumours was examined. p53 expression detected immunocytochemically by the PAb1801 antibody, DNA content evaluated by flow cytometry, and cell proliferation evaluated as the [3H]thymidine labelling index were investigated in primary tumours and corresponding synchronous metastases. The frequency of p53 positivity was similar in primary (62%) and metastatic (66%) sites, with an agreement between the two lesions from the same patient in 97% of the cases. Similarly, aneuploidy frequency (80%) and DNA indices were superimposable in primary and metastatic lesions from the same patient, with a 94% agreement. The frequency of aneuploidy was higher in p53-positive than in p53-negative lesions. An overall poor agreement (rs = 0.44) was observed for proliferative activity of primary and metastatic lesions, due to a heterogeneous profile in omental with respect to primary tumours, which was mainly evident in p53-positive cancers. Conversely, cell proliferation of peritoneal, abdominal and pelvic lesions was qualitatively similar to that of the primary tumour in 88% of patients.     

Incidence of neural tube defects in the Magdeburg administrative district

The Magdeburg Register of birth defects includes information on the incidence rate of neural tube defects (NTD) in the city of Magdeburg since 1980, and in the Regierungsbezirk (administrational district) since 1987. The average prevalence of NTD was 16.4 per 10,000 births in the city of Magdeburg, and 12 per 10,000 births in the surrounding counties. Besides of this significant difference between the city and counties, there are conspicuous variations from one year to the next. In 1987 the prevalence of NTD was about 27 per 10,000 births in the city of Magdeburg whereas the observed prevalence in the countryside was about 19 per 10,000 births. Different eating habits and/or increased teratogenic influences in the city may be considered as causes. In 1997 there was also a high rate of incidence of NTD in the city of Magdeburg--16.4 per 10,000 births. The incidence rate of NTD in the counties (about 10 per 10,000) births) is again lower than in the city. Because of these incidence rates, we may assume that the examined population is insufficiently protected by folic acid in the preconceptional stage.     

Micromechanical properties of epiphyseal trabecular bone and primary spongiosa around the physis: an in situ nanoindentation study

The application of amyloid beta-peptide (Abeta) 1-40 (10 microM) caused neurodegeneration of hippocampal neuronal cells, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Treatment with idebenone (10-1000 nM), a potent antioxidant in mitochondria, protected the hippocampal neurons against the Abeta1-40(10 microM)-induced neurotoxicity. To determine the morphological change in neurons during the Abeta1-40-induced cytotoxicity, the cells were immunostained with anti-MAP2 antibodies. After 4-day exposure to 10 microM Abeta1-40, the number of neurons was reduced, and the surviving neurons had an apparently reduced number of neurites which were shorter than those of control neurons. When idebenone was added to the culture medium with Abeta1-40, the number of surviving neurons was significantly increased, and their neurites were as long as seen in control culture. These results suggest that reactive oxygen species mediate neurotoxicity of Abeta1-40, and idebenone protects neurons against the Abeta1-40-induced neurotoxicity.     

Consolidation of massive bone allografts in limb-preserving operations for bone tumours

Acute renal failure (ARF) is a syndrome in which the kidneys are unable to excrete the products of metabolism. The failure of renal function is rapid in its onset but potentially reversible. It occurs rapidly, within 8 weeks of renal injury resulting in a rapid increase in serum urea and creatinine concentrations in patients with previously normal renal function. It is a condition traditionally associated with a high mortality rate, often due to the complications of sepsis, delayed wound healing and disrupted haemocoagulation. Survivability has been demonstrated to be improved by early appropriate nutritional support (Bartlett et al., 1986) although in practice this is often difficult to achieve as nutritional support is complex. In the past high morbidity and mortality rates were related to infections and inadequate nutritional intake. This resulted from unnecessary protein restrictions in an attempt to control uraemic symptoms (Thomas, 1988). To a large extent survivability of ARF has still not been greatly improved even with modern antibiotics and the careful dietary assessment of ARF patients. This reflects the complexity of managing patients with this condition. However, appropriate dietary management of ARF patients is essential to improve their long-term prognosis. Although the precise form this takes remains a contentious issue amongst clinicians.     

Factor XIIIa immunoreactivity in primary and secondary tumours of the meninges

Occasionally variants of meningeal hemangiopericytomas (HPC) may be confused with primary and secondary tumours of the meninges by virtue of their features and patterns of growth. Until now, a specific immunohistochemical marker for HPC could not be identified. HPC are reported to express factor XIIIa (F XIIIa) in the cytoplasm of the tumour cells. In an effort to assess the diagnostic value of F XIIIa for meningeal HPC, we investigated 38 primary meningeal tumours (6 HPC, 28 meningiomas of various subtypes, 4 meningeal sarcomas) and 23 secondary meningeal tumors (8 metastatic carcinomas, 6 gliosarcomas, 9 anaplastic gliomas) with anti-F XIIIa antibody. All HPC revealed 5%-20% of F-XIIIa-positive neoplastic cells. Malignant fibrous histiocytomas and gliosarcomas with MFH-like structures also exhibited multiple F-XIIIa-positive cells. Most of the F-XIIIa-positive cells in meningiomas were identified as macrophages. Furthermore, there was a population of small dark cells of uncertain histogenesis. Cells with positive immunoreactivity for F-XIIIa in metastatic carcinomas and gliomas apparently were of macrophage lineage. Though, in some cases, it would have been difficult to distinguish reactive from neoplastic cells without simultaneous immunohistochemical investigation with antibodies for macrophages, cytokeratin, EMA and GFAP. Because of these uncertainties, wo believe that the potential of F XIIIa-antibody in obtaining precise differential diagnostic information is limited.     

Incidence of ligament lesions and associated degenerative changes in the elderly wrist

As the carbohydrate lacto-N-fucopentaose III (CD15 antigen or X-determinant) and its sialylated derivative sialyl-Lewis X are involved in the adhesion of cells rolling along the surface of endothelial cells, experiments were done to study the presence of these molecules on human eosinophils from patients with the idiopathic hypereosinophilic syndrome. Normal-density eosinophils from some patients showed higher levels of expression for lacto-N-fucopentaose III than light-density eosinophils. In contrast, sialyl-Lewis X was highly expressed by light-density eosinophils. Activation of normal-density eosinophils with calcium ionophore A23187 resulted in increased expression of these molecules for a short time. Monoclonal antibodies to these carbohydrates stimulated eosinophils to secrete eosinophil cationic protein, but not eosinophil peroxidase, and acted as costimulatory signals for C3b-induced degranulation of eosinophil cationic protein. It was suggested that CD15 and sialyl-Lewis X might contribute to eosinophil-mediated tissue injury in patients with the idiopathic hypereosinophilic syndrome.     

Reimplantation of autoclaved tumour bone in limb salvage surgery

This is a prospective clinical study of 7 patients with malignant bone tumours who were treated by resection of the tumour, followed with reconstruction by reimplantation of the resected autoclaved tumour bone. There were 3 male and 4 female patients between 10 and 36 years of age. All the tumours were Stage IIB. Five of the 7 were in the region of the knee joint. Histologically, 5 were osteosarcomas, 1 a recurrent chondrosarcoma and 1 a recurrent Ewing's sarcoma. All the patients were treated by en bloc resection of the tumour with wide margins. The resected length ranged from 13 cm to 28 cm. After removal of soft tissue and cartilage, the resected bone segment was autoclaved for 5 min at 132 degrees C and 29 pounds per square inch pressure (0.2 mega Pascal). This autoclaved segment of bone was then reimplanted and fixed with an appropriate implant. The average follow-up was 20 months with a range of 14 to 27 months. None of the tumours recurred and, at the most recent follow-up, all the patients were alive, 6 with no evidence of disease and one with a lung metastasis. Six of the 7 patients were available for radiological assessment. Solid bone union was seen in 4 patients, delayed union in 1 and nonunion in 1. This method of reconstruction using an autoclaved tumour bone graft is useful in countries where facilities for allograft or tumour prostheses are not available owing to financial, technical or sociocultural reasons.     

Incidence and prognosis of early primary cardiogenic shock in myocardial infarction

The aim of this retrospective study was to analyse the results of coronary reperfusion on the incidence and short and medium term prognosis of early primary cardiogenic shock in acute myocardial infarction. Of 339 consecutive patients admitted within 6 hours of the onset of acute myocardial infarction, 25 (7.4%) had cardiogenic shock from the onset. The majority of patients (18) underwent direct angioplasty with a successful result in 16 cases. Intravenous thrombolysis was instituted in 5 cases followed by emergency coronary angiography leading to "rescue" coronary angioplasty in 3 cases, which was successful in 2 cases. Two patients had no coronary revascularisation because of a double contra-indication to thrombolysis and catheterization by the femoral approach. Intra-aortic balloon pumping was used in 17 cases. Complementary emergency surgical revascularization was necessary in 5 patients (20%). In all, early reperfusion of the infarct-related artery was obtained in 80% of cases (20 patients). The hospital mortality was 72% (18 patients) due to refractory cardiac failure in nearly all cases. After an average follow-up of 17 months, 3 of the 7 survivors of the hospital period have died and of the 4 remaining patients, 2 are in the NYHA classes III or IV. Recent therapeutic advances have not influenced the incidence of cardiogenic shock but have significantly increased the proportion of very early cardiogenic shock, whereas the late cardiogenic shocks of more progressive onset, have nearly disappeared (4/339, 1.2% in this series). The prognosis of these early shocks, caused by severe myocardial damage, remains catastrophic and hardly improved by emergency coronary reperfusion by angioplasty and intraaortic balloon pumping.(ABSTRACT TRUNCATED AT 250 WORDS)