S.F. Ahmed

Consensus statement on management of intersex disorders

The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

The role of a clinical score in the assessment of ambiguous genitalia

Objective To improve the initial assessment of ambiguous genitalia in infants.

The impact of corticosteroids on growth and bone health

An examination of current evidence Glucocorticoids (GC) are important regulators of diverse physiological systems and are often used in the treatment of a number of chronic inflammatory, autoimmune, and neoplastic diseases. It is estimated that 10% of children may require some form of GC at some point in their childhood.1 Impairment of childhood growth with an approximate cortisone dose of 1.5 mg/kg/day was first described over 40 years ago; osteopenia in children receiving a prednisolone dose of less than 0.16 mg/kg/day has also been reported.2,3 The maintenance of growth and bone health is a complex process that can be influenced not only by drugs, but also by the nutritional status of the patient and the underlying disease process. The purpose of this review is to examine the current evidence for linking GC to adverse growth and bone health in childhood disorders that commonly require GC therapy. Loss of bone and deterioration in short term growth are dependent on the type and dose of GC and occur most prominently over the first six months of treatment.4–6 Although it is generally believed that GC affect trabecular bone more than cortical bone, a recent study of fractures in children following steroid exposure as part of acute lymphoblastic leukaemia (ALL) treatment showed a high incidence of cortical bone involvement, suggesting that the disease process may interact with GC usage in influencing site of bone loss.7,8 GC have a suppressive effect on osteoblastogenesis in the bone marrow and promote the apoptosis of osteoblasts and osteocytes, thus leading to decreased bone formation.9 Accumulation of apoptotic osteocytes may also explain the so called “osteonecrosis”, also known as aseptic or avascular necrosis. There is some evidence to suggest that GC may also increase bone resorption by extending the lifespan of …

Recent trends and clinical features of childhood vitamin D deficiency presenting to a children's hospital in Glasgow

Background The incidence of vitamin D deficiency is unclear in the context of continuing demographic changes and the introduction of new public health measures. Methods All cases in which vitamin D deficiency was suspected as the primary cause of the clinical presentation were studied. Results Between 2002 and 2008, 160 cases of symptomatic vitamin D deficiency were identified with twice as many cases in 2008 (n, 42) as in the previous years. The median age of the cohort was 24 months (range 2 weeks-14 years).Three cases were recorded in children of European background, whereas the rest were in children of South Asian, Middle Eastern or sub-Saharan ethnic background. Presenting features included bowed legs in 64 (40%) and a fit in 19 (12%). In one infant, concerns were raised following a presentation with cardiac failure and hypocalcaemia. Summary Symptomatic vitamin D deficiency remains prevalent in the West of Scotland. There is a need for effective public health education, action and surveillance.

The effect of GH and IGF1 on linear growth and skeletal development and their modulation by SOCS proteins

Circulating signalling proteins have often been divided into hormones and cytokines, but it is increasingly being recognised that these substances have a number of common characteristics and mechanisms of action. This is clearly illustrated by the suppressor of cytokine signalling (SOCS) proteins which are increasingly seen as a central component of the regulation of the action of hormones and cytokines that signal through the cytokine receptor complex. The SOCS protein family is probably more extensive than currently recognised; its members may have differential tissue expression and their potency for suppressing cytokine signalling may vary. Recent knockout and transgenic studies in mice have highlighted the role that these proteins play in growth and skeletal development as well as in inflammation. Chronic inflammation is associated with altered growth and skeletal development, and it is possible that SOCS proteins may have an important role to play in mediating these effects.

Prevalence of hypospadias and other genital anomalies among singleton births, 1988-1997, in Scotland.

Background: Considerable debate exists on the epidemiology of genital anomalies. Methods: All genital anomalies, excluding undescended testes, were identified from neonatal returns, stillbirth and infant death survey records, and returns relating to hospital admissions and linked to form infant profiles on a cohort of singleton births between 1988 and 1997 with follow up for a minimum of three years. Findings: The mean genital anomaly prevalence rate in Scotland was calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9 per 1000 births in 1996. However, there was no evidence of a clear trend to an increasing prevalence of hypospadias, which constituted 73% of the anomalies studied. Logistic regression analysis of the data also showed this rate to be independently associated with being relatively small for gestational age (odds ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05). Infants born in deprived areas, as judged by the Carstairs deprivation score, were least likely to have a genital anomaly (OR 0.73, p < 0.01). Interpretation: A new linked register of congenital genital anomalies in Scotland suggests that over a decade, the birth prevalence of genital anomalies has changed little. The associations between genital anomalies, maternal age, and socioeconomic deprivation require further study.

Invasive pneumococcal disease in Scotland, 1999-2001: use of record linkage to explore associations between patients and disease in relation to future vaccination policy.

A record linkage study was done to provide comprehensive data on the epidemiologic characteristics of invasive pneumococcal disease (IPD) in Scotland. The overall incidence of IPD was 11 cases/10(5) persons and 21 cases/10(5) persons <1 year of age, 51 cases/10(5) persons 1 year of age, 45 cases/10(5) elderly persons (age > or =65 years), 176-483 cases/10(5) persons with chronic medical conditions, and 562-2031 cases/10(5) persons with severe immunosuppression. The case-fatality rate was 11% among elderly persons and ranged from 3% to 13% among persons with underlying medical conditions. The most common pneumococcal serogroups associated with IPD were 14, 9, 6, 19, 23, 8, and 4. Serogroups included in the 23-valent polysaccharide vaccine caused the majority of cases of IPD. The proportion of IPD due to the 7-, 9-, and 11-valent conjugate vaccine serogroups was lower among older people and persons with underlying medical conditions.

Lethal outbreak of infection with Clostridium novyi type A and other spore-forming organisms in Scottish injecting drug users

This report describes the investigation and management of an unprecedented outbreak of severe illness among injecting drug users (IDUs) in Scotland during April to August 2000. IDUs with severe soft tissue inflammation were prospectively sought among acute hospitals and a mortuary in Scotland. Cases were categorised as definite or probable: probable cases had severe injection site inflammation or multi-system failure; definite cases had both. Information about clinical course, mortality, post-mortem findings and laboratory data was gathered by standardised case-note review and interview. Sixty cases were identified--23 definite and 37 probable. Most had familial or social links with each other and 50 were from Glasgow. Median age was 30 years; 31 were female. The majority, especially definite cases, injected heroin/citric acid extravascularly. Of definite cases, 20 died (87% case-fatality rate; 13 after intensive care), 15 had necrotising fasciitis, 22 had injection site oedema and 13 had pleural effusion. Median white cell count was 60 x 10(9)/L. Of 37 probable cases, three died (8% case-fatality rate). Overall, the most frequently isolated pathogen was Clostridium novyi type A (13 cases: 8 in definite cases). The findings are consistent with an infection resulting from injection into soft tissue of acidified heroin contaminated with spore-forming bacteria. Toxin production led to a severe local reaction and, in many, multi-system failure.

The role of sex steroids in controlling pubertal growth.

Longitudinal growth, which is primarily due to chondrocytic activity at the level of the epiphyseal growth plate, is influenced by many hormones and growth factors in an endocrine and paracrine manner. Their influence is even more complex during the accelerated growth period of puberty that accounts for about 20% of final adult height. Although abnormalities of growth during puberty are very common, the underlying mechanisms that govern the beginning and cessation of pubertal growth at the level of the growth plate are poorly understood. Sex steroids play a crucial role in pubertal growth both at the systemic level via the GH/IGF‐1 axis and at the local level of the epiphyseal growth plate. In both sexes it is now accepted that oestrogen is the critical hormone in controlling growth plate acceleration and fusion. This paper reviews the mechanisms that influence pubertal growth and the problems that are associated with disorders of gonadal function.

Epidemiological investigation of the Central Scotland outbreak of Escherichia coli O157 infection, November to December 1996

On Friday, 22 November 1996, the microbiologist at a hospital in Lanarkshire, Scotland, identified presumptive Escherichia coli O157 in faecal specimens submitted by three patients with bloody diarrhoea, and confirmed its presence in one. Over the next 6 h, 12 more potential cases were identified. Investigations first indicated then confirmed a single food premises as the source of infection. Effective control measures were applied promptly. The outbreak was declared over on 20 January 1997, by which time 512 cases had been identified, and infection with the outbreak strain confirmed in 279. Twenty deaths occurred in cases during the outbreak and there were two more in cases during 1997. Seventeen of these deaths resulted from the outbreak. This paper describes the outbreaks epidemiological investigation, referring to other investigations, and control measures, where appropriate.