Cancer symptom awareness and barriers to symptomatic presentation in England--are we clear on cancer?

BACKGROUND: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. METHODS: Using a uniquely large data set (n=49 270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. RESULTS: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor's surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. CONCLUSIONS: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes.

Mediastinal necrosis in acute pancreatitis - case report.

Ascites, pseudocyst, necrosis of the retroperitoneal fat tissue and pancreatopleural fistula with left sided pleural effusion may complicate pancreatitis. However, steatonecrosis of the mediastinum and right side pleural effusion are rather rare complications of pancreatitis. We present a case of a patient with alcohol induced pancreatitis. Chest x-ray showed right sided pleural effusion. Although high levels of amylase in pleural fluid made the diagnosis of pancreatopleural fistula most likely, necrosis of the mediastinal fat tissue with right side pleural effusion was found postmortem.

Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element.

In monosymptomatic forms of cystic fibrosis such as congenital bilateral absence of vas deferens, variations in the TG(m) and T(n) polymorphic repeats at the 3' end of intron 8 of the cystic fibrosis transmembrane regulator (CFTR) gene are associated with the alternative splicing of exon 9, which results in a nonfunctional CFTR protein. Using a minigene model system, we have previously shown a direct relationship between the TG(m)T(n) polymorphism and exon 9 splicing. We have now evaluated the role of splicing factors in the regulation of the alternative splicing of this exon. Serine-arginine-rich proteins and the heterogeneous nuclear ribonucleoprotein A1 induced exon skipping in the human gene but not in its mouse counterpart. The effect of these proteins on exon 9 exclusion was strictly dependent on the composition of the TG(m) and T(n) polymorphic repeats. The comparative and functional analysis of the human and mouse CFTR genes showed that a region of about 150 nucleotides, present only in the human intron 9, mediates the exon 9 splicing inhibition in association with exonic regulatory elements. This region, defined as the CFTR exon 9 intronic splicing silencer, is a target for serine-arginine-rich protein interactions. Thus, the nonevolutionary conserved CFTR exon 9 alternative splicing is modulated by the TG(m) and T(n) polymorphism at the 3' splice region, enhancer and silencer exonic elements, and the intronic splicing silencer in the proximal 5' intronic region. Tissue levels and individual variability of splicing factors would determine the penetrance of the TG(m)T(n) locus in monosymptomatic forms of cystic fibrosis.

Functional analysis of cis-acting elements regulating the alternative splicing of human CFTR exon 9.

The rate of exon 9 exclusion from the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA is associated with monosymptomatic forms of cystic fibrosis. Exon 9 alternative splicing is modulated by a polymorphic polythymidine tract within its 3' splice site. We have generated a minigene carrying human CFTR exon 9 with its flanking intronic sequences and set up an in vivo model to study the cis-acting DNA elements which modulate its splicing. Transfections into human cell lines showed that T5, but not T9 or T7 alleles, significantly increases the alternative splicing of exon 9. Moreover, we found that another polymorphic locus juxtaposed upstream of the T tract, and constituted by (TG)(n)repeats, can further modulate exon 9 skipping but only when activated by the T5 allele. Then, we extended our studies to the mouse CFTR exon 9 which does not show alternative splicing. Comparison of human and mouse introns 8 and 9 revealed a low homology between the two sequences and the absence of the human polymorphic loci within the mouse intron 3' splice site. We have tested a series of constructs where the whole human exon 9 with its flanking intronic sequences was replaced partially or completely by the murine counterpart. The transfections of these constructs in human and murine cell lines reveal that also sequences of the downstream intron 9 affect exon 9 definition and co-modulate, with the UG/U 3' splice site sequences, the extent of exon 9 skipping in CFTR mRNA.

Association between deletion polymorphism of the angiotensin-converting enzyme gene and cerebral atherosclerosis.

We investigated deletion polymorphism in the gene for angiotensin-converting enzyme in patients with angiographically verified cerebral atherosclerosis. Genotypes were determined by the polymerase chain reaction with oligonucleotide flanking of the polymorphic region of intron 16 of the angiotensin-converting enzyme gene. Results of angiotensin-converting enzyme genotyping showed 46% of 50 studied patients to be homozygous for the DD allele, whose prevalence was significantly increased as compared with a group of controls without atherosclerotic changes. In this control group, the following genotypes were observed (%): II = 24, ID = 52 and DD = 24. The frequency of the I and D alleles in the group of patients with cerebral atherosclerosis was 0.28 and 0.72, respectively, whereas in the group without atherosclerosis it was 0.50 for both. Furthermore, in the present study, the DD genotype was associated with a high level of serum angiotensin-converting enzyme activity, total and LDL-cholesterol and triacylglycerol. A newly established association between DD genotype and cerebral atherosclerosis, detected even in our small group, supports the view that angiotensin-converting enzyme polymorphism might be indicative of the development of cerebral atherosclerosis.

[Intravascular coagulation fibrinolysis syndrome (ICF) in patients with epipharyngeal juvenile angiofibroma (author's transl)]. / Verbrauchskoagulopathie bei Patienten mit juvenilem Angiofibrom.

In two patients with epipharyngeal juvenile angiofibroma we could find coagulation disorders in the sense of the disseminated intravascular coagulation fibrinolysis syndrome (IFC), which was clinically latent before, but became manifest during or after surgery. The author tries to explain the mechanism of its development.

[Immunglobulins in serum of laryngeal and pharyngeal cancer patients (author's transl)]. / Die Serumimmunglobuline bei Patienten mit Malignomen des Kehlkopfs und des Rachens

The majority of our laryngeal and pharyngeal cancer patients had increased serum immunoglobulin values, which normalised in nearly all of the patients examined six month after successful surgical treatment. The decreased values of the serum immunoglobulins were found in patients with advanced tumours as well as in those with T1 and T2 tumours. Some of these latter patients also had a deficient cellular immune response, and it is likely that a combined immune deficiency was the leading factor which caused the malignancy in those patients.

[Coagulation abnormalities in the patients with malignant tumours of the larynx and pharynx (author's transl)]. / Uber Gerinnungsstörungen bei Kehlkopf- und Rachen-malignomen

In 8 of 41 examined patients with larynx tumour and in 6 of 7 those with pharynx tumours we found hypercoagulability using specific coagulation test. In two of our patients laboratory tests pointed out on the disseminated intravascular coagulation, that became clinically manifest just during radiotherapy. The routine coagulation tests cannot detect the coagulation abnormality in the majority of cases and therefore in the patients with malignant tumours specific tests for discovering the ICF (intravascular coagulation and fibrinolysis) syndrom are to be made.