Multiple Cerebral Haematomata and Peripheral Nerve Palsies Associated with a Case of Juvenile Diabetic Ketoacidosis

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.     

International cancer patterns in men: geographical and temporal variations in cancer risk and the role of gender

The comparison of disease risk in populations stratified by certain demographic variables provides important clues as to the underlying causes of disease. There are fundamental variations in the risk of occurrence of different cancers by gender, area of residence, and time of diagnosis. Men are, for instance, at considerably higher risk of developing most of the common cancers that occur in both sexes, and there are substantial variations in the occurrence of particular cancers in different regions of the World. This paper attempts to highlight some of these remarkable variations using cancer incidence data by sex, area of residence and year of diagnosis, emphasising the strong evidence that many of the contrasts can be appropriated to a number of modifiable “environmental” factors.Rates of cancer occurrence in the developed world are double that of less developed regions, although risk patterns are of very different magnitude and direction depending on the cancer site examined. Lung cancer is the most common neoplasm in men globally, but is overshadowed by prostate cancer in certain westernised countries, notably in the U.S. Cancers of the colon and rectum are important in the developed world, whereas stomach and liver cancer are common in developing areas.Men have systematically higher rates than women for the vast majority of the tumours that develop in both sexes, with the exception of thyroid cancer. There are also huge variations in the extent of the inequality: men have notably elevated risks, relative to women, of developing tumours of the head and neck, bladder, lung, oral cavity and liver.In Europe, incidence trends of lung cancer tend to be declining in men, although there is substantial between-country variation. In women, lung cancer rates are systematically on the increase in most Western, Southern and European countries. Trends in prostate cancer are increasing, as are trends in colorectal cancer (in both sexes), although more noticeably in Southern and Eastern Europe. Stomach cancer continues to fall in most European areas. Bladder cancer is decreasing in both men and women, apart from in Eastern Europe, whereas cancers of the kidney and non-Hodgkin lymphoma are steadily increasing in both sexes.We have estimated that men have better and more readily achievable prospects of avoiding death from cancer since they have lower rates of gender specific cancers, that are probably hormonal in origin, then women. Tobacco consumption plays a dominating role in the excess risk of cancer in men but it is apparent that the male excess disease burden can be effectively reduced by various prevention measures. As well as avoiding (or quitting) smoking, these include, moderating alcohol consumption, avoiding obesity, undertaking regular physical exercise, and maintaining a diet high in fruit and vegetables. The adoption of a healthier lifestyle will be of considerable benefit to the general health of both men and women, with an expectation of a major reduction in the burden of cancer, as well as other major diseases.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

The expression of somatostatin receptors 1 and 2 in benign,pre‐malignant and malignant laryngeal lesions

The expression of somatostatin receptors 1 and 2 in benign, pre‐malignant and malignant laryngeal lesions The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane‐bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre‐malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre‐malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low‐to‐moderate levels in only 2/6 (33%) pre‐malignant and 3/12 (25%) malignant specimens (P < 0.01). This ‘loss’ of epithelial SSTR2 expression may provide a growth advantage in pre‐malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre‐malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.