The enigma of pain

The unusual subject of pain in all its forms is explored at a recently opened Wellcome Trust exhibition at the Science Museum in London. Arveen Bajaj speaks to the exhibition's curator, Javier Moscoso, about the themes, ideas and insights behind the exhibition.     

Chromosome 17q12 duplications: Further delineation of the range of psychiatric and clinical phenotypes

Copy number variants at chromosome 17q12 have been associated with a spectrum of phenotypes. Deletions of 17q12 are well described and associated with maturity onset diabetes of the young type 5 (MODY5) and cystic renal disease (HNF1β) as well as cognitive impairment and seizures. Duplication of 17q12 is emerging as a new genetic syndrome, associated with learning disability, seizures, and behavioral problems. The duplication is often inherited from an apparently unaffected parent. Here, we describe a three‐generation family with multiple individuals carrying a17q12 microduplication with varying clinical features, consistent with variable penetrance. The proband who inherited a 1.8 Mb interstitial 17q12 duplication from his mother presented with developmental delay, behavioral problems, and mild dysmorphism. One of his sisters, his maternal uncle, and his maternal grandmother also carry the 17q12 microduplication. Clinical features of the carriers include renal problems, diabetes mellitus, learning difficulties, epilepsy and mental illness. Cognitive abilities range from normal function to moderate impairment (full‐scale IQ range: 52‐99). In light of recent reports of association of this locus with schizophrenia, we performed a detailed psychiatric assessment and confirmed that one family member has symptoms consistent with a diagnosis of schizophrenia and another has a prodromal syndrome with attenuated positive symptoms of psychosis. This report extends the clinical phenotype associated with the 17q12 microduplication and highlights the phenotypic variability.     

Disaster victim identification: Tsunami

In the aftermath of the devastating tsunami that hit South East Asia last December, a huge operation to try to identify thousands of victims got underway, with the help of many overseas medical and dental professionals. British dentist Gareth Pearson went to Thailand to try and help in this task and here recounts his experience.     

Genetic and genomic investigations in the neonatal intensive care unit

Genetic testing is available and widely used in the neonatal intensive care setting for a broad range of complex presentations arising both antenatally and in the postnatal period. Here we discuss the investigations currently available to clinicians in the neonatal intensive care unit, such as array comparative genomic hybridization (aCGH), FISH (fluorescent in situ hybridization) and quantitative florescent polymerase chain reaction (QF-PCR), later looking to the future of clinical genomic testing, in the form of next generation sequencing panels (NGS panels), whole exome (WE) and whole genome (WG) sequencing. The mainstreaming of genetic medicine requires non-genetic specialists, such as neonatologists and paediatricians, to have confidence and knowledge of the testing process, the technologies available and the ethical and social considerations associated with their use.     

Perforated Peptic Ulcer in South India: An Institutional Perspective

Background  Perforated peptic ulcer is one of the most common surgical emergencies in South India. The advent of medical therapy for peptic ulcer has remarkably decreased the number of elective surgical procedures. The incidence of perforated peptic ulcer on the contrary, is increasing. The high incidence of complications necessitates the identification of factors associated with the morbidity and mortality of patients undergoing surgery for perforated peptic ulcer. Methods  Three hundred twenty-eight consecutive patients (299 men and 29 women) who underwent surgery for perforated peptic ulcer in our institute between November 2006 and June 2008 were studied prospectively. Results  The mean age was 43.4 ± 14.4 years. The mean hospital stay was 10.9 ± 6.8 days. Of the 328 patients, 58 presented with shock, 159 presented with delay more than 24 h, and 24 had co-morbid illness. Wound infection and intra-abdominal abscess were encountered in 12.5% and 13.4% of the patients, respectively. Altogether, 85 patients had postoperative complications. Twenty-eight (8.5%) patients died. The mortality rate among men and women was 7.9% and 20.7%, respectively. Age ≥ 60 years, lag period longer than 24 h, presence of co-morbid illness, and shock at presentation were identified as independent predictors of postoperative complications. Shock at presentation, presence of co-morbid illness, American Society of Anesthesiologists (ASA) grade III or more, and renal failure were identified as independent predictors of mortality. Conclusions  Decreasing the delay in intervention and improving access to medical care may improve the outcome of patients undergoing surgery for perforated peptic ulcer. High-risk patients are those who present with shock and co-morbid illness.     

Fairy tales

Everyone knows the story of the tooth fairy, but fine art degree student Cordelia Cembrowicz has transformed the mythical figure in a most unusual way.     

The role of open radical nephrectomy in contemporary management of renal cell carcinoma

Radical nephrectomy (RN) remains a cornerstone of the management of localised renal cell carcinoma (RCC). RN involves the en bloc removal of the kidney along with perinephric fat enclosed within Gerota’s fascia. Key principles of open RN include appropriate incision for adequate exposure, dissection and visualisation of the renal hilum, and early ligation of the renal artery and subsequently renal vein. Regional lymph node dissection (LND) facilitates local staging but its therapeutic role remains controversial. LND is recommended in patients with high risk clinically localised disease, but its benefit in low risk node-negative and clinically node-positive patients is unclear. Concomitant adrenalectomy should be reserved for patients with large tumours with radiographic evidence of adrenal involvement. Despite a recent downtrend in utilisation of open RN due to nephron-sparing and minimally invasive alternatives, there remains a vital role for open RN in the management of RCC in three domains. Firstly, open RN is important to the management of large, complex tumours which would be at high risk of complications if treated with partial nephrectomy (PN). Secondly, open RN plays a crucial role in cytoreductive nephrectomy (CN) for metastatic RCC, in which the laparoscopic approach achieves similar results but is associated with a high reoperation rate. Finally, open RN is the current standard of care in the management of inferior vena caval (IVC) tumour thrombus. Management of tumour thrombus requires a multidisciplinary approach and varies with cranial extent of thrombus. Higher level thrombus may require hepatic mobilisation and circulatory support, whilst the presence of bland thrombus may warrant post-operative filter insertion or ligation of the IVC.     

Dilemmas and controversies in penicillin allergy

Since the initial reports of penicillin and beta-lactam drugs causing allergic reactions, much has been elucidated regarding their pathophysiology and mechanism of action. Despite advances in testing for penicillin allergy, with IgE antibodies and skin tests available for the major and minor determinants of penicillin, these reactions remain a challenge to all physicians. They have characteristically been classified according to mechanism and time. Herein, the authors propose a classification system of penicillin allergy based on immunologic mechanisms.