Retinoblastoma gene abnormalities in early laryngeal cancer

The retinoblastoma gene (Rb) is postulated to be important in carcinoma of the larynx. Its cellular protein (pRb) is involved in regulation of the cell cycle and may be influential in the cells response to irradiation injury. From the University of Liverpool Head and Neck Database we identified 35 patients with a T2 N0 laryngeal squamous carcinoma whom received primary irradiation and had a minimum of 5 years follow up. Laser capture microdissection was performed on paired normal and tumour biopsy material to analyse for loss of heterozygosity (LOH) and microsatelite instability (MI) of the Rb gene and immunohistochemistry (IHC) was carried out to detect pRb expression. Of 35 tumours, 13 were normal, 12 had MI and 5 had LOH of the Rb gene. Abnormalities at the Rb locus did not correlate with loss of pRb expression. There was also no significant difference between the distribution of normal and abnormal gene sequences and whether or not the primary laryngeal tumour recurred after radiotherapy. Rb gene abnormalities occurred in one third of T2 N0 laryngeal carcinomas. These were not in isolation predictive of cure by radiotherapy.     

Isolated hypoglossal nerve palsy: a harbinger of malignancy

The hypoglossal nerve is an underrated nerve usually consigned to a few words in anatomical text books, under the last four cranial nerves. However, paralysis of this nerve may be the first indication of a serious underlying disorder. Excluding previous surgery, radiotherapy and trauma, 50 per cent of cases of isolated hypoglossal nerve palsy are idiopathic. A further 20 per cent are malignant, 20 per cent are vascular and 10 per cent are due to miscellaneous causes. Presentation of an isolated hypoglossal nerve palsy is therefore an ominous sign. There is confusion over both cause and investigation, and management protocols for isolated hypoglossal nerve palsy are ill-defined. We present a case of isolated hypoglossal palsy which was due to a metastatic skull base deposit. This case illustrates the fact that magnetic resonance imaging is the investigation of choice in assessing the entire course of the hypoglossal nerve.     

Understanding chronic heart failure

The key principles of chronic heart failure and the development of clinical management strategies are described. The physiological changes in chronic heart failure and the clinical management of children with heart failure are considered, but the treatment of heart failure related to congenital heart disease or the intensive care management of heart failure are not mentioned as both topics require consideration in their own right. A greater understanding of the maladaptive responses to chronic heart failure has enabled targeted therapy to be introduced with consequent improvement in symptoms, reduction in hospitalisation and lower mortality.     

Incidence and reinfection rates of genital chlamydial infection among women aged 16-24 years attending general practice, family planning and genitourinary medicine clinics in England: a prospective cohort study by the Chlamydia Recall Study Advisory Group

BACKGROUND: In England, screening for genital chlamydial infection has begun; however, screening frequency for women is not yet determined. AIM: To measure chlamydia incidence and reinfection rates among young women to suggest screening intervals. METHODS: An 18-month prospective cohort study of women aged 16-24 years recruited from general practices, family planning clinics and genitourinary medicine (GUM) clinics: baseline-negative women followed for incidence and baseline-positive women for reinfection; urine tested every 6 months via nucleic acid amplification; and behavioural data collected. Extra test and questionnaire completed 3 months after initial positive test. Factors associated with infection and reinfection investigated using Cox regression stratified by healthcare setting of recruitment. RESULTS: Chlamydia incidence was mean (95% CI) 4.9 (2.7 to 8.8) per 100 person-years (py) among women recruited from general practices, 6.4 (4.2 to 9.8) from family planning clinics and 10.6 (7.4 to 15.2) from GUM clinics. Incidence was associated with young age, history of chlamydial infection and acquisition of new sexual partners. If recently acquiring new partners, condom use at last sexual intercourse was independently associated with lower incidence. Chlamydia reinfection was mean (95% CI) 29.9 (19.7 to 45.4) per 100/person-year from general practices, 22.3 (15.6 to 31.8) from family planning clinics and 21.1 (14.3 to 30.9) from GUM clinics. Factors independently associated with higher reinfection rates were acquisition of new partners and failure to treat all partners. CONCLUSIONS: Sexual behaviours determined incidence and reinfection, regardless of healthcare setting. Our results suggest annual screening of women aged 16-24 years who are chlamydia negative, or sooner if partner change occurs. Rescreening chlamydia-positive women within 6 months of baseline infection may be sensible, especially if partner change occurs or all partners are not treated.     

Pseudohypoparathyroidism type 1a with congenital hypothyroidism

Pseudohypoparathyroidism type la (PHP-1a) is an uncommon disorder that results from an inactivating mutation in the GNAS gene. It can present with resistance to several hormones, in addition to parathyroid hormone (PTH). Patients may have the classic Albright's hereditary osteodystrophy (AHO) phenotype and can develop resistance to thyroid stimulating hormone (TSH), gonadotropins, growth hormone releasing hormone (GHRH), and other hormones that rely on the Gsalpha protein to regulate signal transmission at their receptors. We report two siblings with PHP-1a and congenital hypothyroidism. The patients were found to have a heterozygous mutation at nucleotide 305 in exon 4 (c305C-->A) of the GNAS gene, which has not been previously linked to congenital hypothyroidism.