Showing papers by "Wishaw General Hospital published in 2014"

Pharmacogenomics in psychiatry: the relevance of receptor and transporter polymorphisms

Abstract: The treatment of severe mental illness, and of psychiatric disorders in general, is limited in its efficacy and tolerability. There appear to be substantial interindividual differences in response to psychiatric drug treatments that are generally far greater than the differences between individual drugs; likewise, the occurrence of adverse effects also varies profoundly between individuals. These differences are thought to reflect, at least in part, genetic variability. The action of psychiatric drugs primarily involves effects on synaptic neurotransmission; the genes for neurotransmitter receptors and transporters have provided strong candidates in pharmacogenetic research in psychiatry. This paper reviews some aspects of the pharmacogenetics of neurotransmitter receptors and transporters in the treatment of psychiatric disorders. A focus on serotonin, catecholamines and amino acid transmitter systems reflects the direction of research efforts, while relevant results from some genome-wide association studies are also presented. There are many inconsistencies, particularly between candidate gene and genome-wide association studies. However, some consistency is seen in candidate gene studies supporting established pharmacological mechanisms of antipsychotic and antidepressant response with associations of functional genetic polymorphisms in, respectively, the dopamine D2 receptor and serotonin transporter and receptors. More recently identified effects of genes related to amino acid neurotransmission on the outcome of treatment of schizophrenia, bipolar illness or depression reflect the growing understanding of the roles of glutamate and γ-aminobutyric acid dysfunction in severe mental illness. A complete understanding of psychiatric pharmacogenomics will also need to take into account epigenetic factors, such as DNA methylation, that influence individual responses to drugs.

Reduced fetal growth in methadone-maintained pregnancies is not fully explained by smoking or socio-economic deprivation.

Abstract: Aim To determine if reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is explained by cigarette smoking or socio-economic deprivation. Design Retrospective cohort study. Setting Inner-city maternity unit in Scotland. Participants A total of 366 singleton infants of methadone-prescribed opioid-dependent mothers compared with the Scottish birth population (n = 103 366) as a whole. Measurements Primary outcome measures were birth weight and head circumference. Findings In infants of methadone-prescribed opioid-dependent mothers mean birth weight was 259 g [95% confidence interval (CI) 214–303 g; P < 0.0001] less, and mean head circumference 1.01 cm (95% CI 0.87–1.15 cm; P < 0.0001) less than in controls, allowing for gestation, cigarette smoking, area deprivation, infant sex and maternal age and parity. This represents an adjusted difference of −0.61 (95% CI −0.52–−0.71; P < 0.0001) Z-score in mean birth weight and −0.77 (95% CI −0.66–−0.89; P < 0.0001) Z-score in mean head circumference. Conclusions Reduced fetal growth in infants of opioid-dependent mothers prescribed methadone maintenance in pregnancy is not fully explained by cigarette smoking, area deprivation, maternal age or parity.

Comorbidities in lung cancer: prevalence, severity and links with socioeconomic status and treatment

Abstract: Background Survival from lung cancer remains poor in Scotland, UK. Although the presence of comorbidities is known to influence outcomes, detailed quantification of comorbidities is not available in routinely collected audit or cancer registry data. The aim of the present study was to assess the prevalence and severity of comorbidities in patients with newly diagnosed lung cancer across four centres throughout Scotland using validated criteria. Methods Between 2005 and 2008, all patients with newly diagnosed lung cancer coming through the multidisciplinary teams in four Scottish centres were included in the study. Patient demographics, WHO/Eastern Cooperative Oncology Group performance status, clinicopathological features and primary treatment modality were recorded. Results Details of 882 patients were collected prospectively. The majority of patients (87.3%) had at least one comorbidity, the most common being weight loss (53%), chronic obstructive pulmonary disease (43%), renal impairment (28%) and ischaemic heart disease (27%). A composite score was produced that included both number and severity of comorbidities. One in seven patients (15.3%) had severe comorbidity scores. There were statistically significant variations in comorbidity scores between treatment centres and between non-small cell lung carcinoma treatment groups. Disease stage was not associated with comorbidity score. Conclusions There is a high prevalence of multiple, severe comorbidities in Scottish patients with lung cancer, and these vary by site and treatment group. Further research is needed to determine the relationship between comorbidity scores and survival in these patients.

Recent advances of hemorrhage management in severe trauma.

Abstract: Trauma is one of the most common causes of mortality worldwide with a substantial percentage of deaths resulting secondary to haemorrhages, which are preventable and treatable when adequately managed This paper offers a review of the current literature on how to successfully resuscitate patients with major haemorrhage

Polymorphisms of serotonin neurotransmission and their effects on antipsychotic drug action

Abstract: The receptor pharmacology of many antipsychotic drugs includes actions at various serotonin (5-hydroxytryptamine [5-HT]) receptors. The 5-HT neurotransmitter system is thought to be involved in many of the consequences of treatment with antipsychotic drugs, including both symptom response, primarily of negative and depressive symptoms, and adverse effects, notably extrapyramidal side effects and weight gain. There is substantial interindividual variability in these drug effects, to which genetic variability contributes. We review here the influence of functional polymorphisms in genes associated with 5-HT function, including the various processes of neurotransmitter synthesis, receptors, transporters and metabolism, on the clinical response to, and adverse effects of, antipsychotic drugs. The relatively young field of epigenetics also contributes to the variability of 5-HT-related genes in influencing drug response. Several of these findings inform our understanding of the mechanisms of antipsychotic drug action, and also provide the opportunity for the development of genetic testing for personalized medicine.

Langerhans cell histiocytosis: 23 years’ paediatric experience highlights severe long-term sequelae:

Abstract: PurposeTo review the presentation and outcome of patients with Langerhans cell histiocytosis attending The Royal Hospital for Sick Children, Glasgow over a 23-year period.MethodThirty-one children ...

Severe congenital herpes simplex virus infection

Abstract: A preterm baby boy was delivered at 29 weeks of gestation following preterm labour. He was ventilated due to poor respiratory effort. His skin was unusually translucent, fragile, red and prominently vascularised. There were sparse pustules and areas of superficial ulceration and sloughing, especially on the face as shown in figure 1. His growth was appropriate for gestational age. Umbilical lines were sited in view of condition of the skin and …

Gas gangrene presenting with back pain.

Abstract: A 61-year-old Caucasian man (previously fit and well) presented to the emergency department with 2 days of non-traumatic, non-radiating lower back pain. He was admitted to our department having been provisionally diagnosed with discitis. Later that night, while being reassessed, a skin lesion on his thigh appeared and gas could be palpated. The patient was then taken immediately to theatre and a radical surgical debridement was performed. The organism that grew from tissue samples was Clostridium septicum, which when identified is an indication to exclude colonic neoplasms. The patient managed to preserve his limb on this occasion, however, he underwent a right hemicolectomy for what proved to be a colonic tumour at a later date.

Rectal obliteration following stapled haemorrhoidopexy: a new endoscopic approach to restore luminal continuity

Abstract: Dear Sir, Life threatening complications following stapled haemorrhoidopexy are uncommon and include rectal perforation, sepsis, bleeding and rectal obstruction [1,2]. There are only a few reported cases of rectal obliteration after stapled haemorrhoidopexy, also known as the procedure for prolapse and haemorrhoids (PPH), which is widely accepted for the treatment of haemorrhoids and rectal mucosal prolapse [3–6]. Data from the literature show a complication rate ranging from 5% to 45% with reoperation in 11% [2,6]. We performed stapled haemorrhoidopexy on a 60year-old lady for circumferential haemorrhoids and partial thickness rectal prolapse using an Ethicon PPH03 instrument. The standard technique was followed with the purse string placed circumferentially 4 cm proximal to the dentate line leaving no gaps between the sutures. The suture was tied around the examining digit to ensure the presence of a lumen before insertion, closure and firing of the stapler. After firing, however, complete rectal obliteration was identified on digital examination. The doughnut was examined and a complete disc of mucosa was found (Fig. 1). An attempt to pass a fine probe through the obstructed site was not successful. The only remaining option was to perform a laparoscopic loop colostomy to relieve the obstruction. Following recovery from the operation a radiocontrast study confirmed the presence of luminal obliteration (Fig. 2a). After discussion with the patient, corrective surgery was performed 3 weeks after the initial operation. A gastroscope was inserted down the distal limb of the loop colostomy (Fig. 3) The light of the instrument was seen on inspection by an eisenhammer rectal speculum introduced into the rectum at the site of the obliteration. A cannula from a percutaneous endoscopic gastroscopy pack was then inserted from below through the centre of the obliterated rectal mucosa under direct vision, following which a guide wire was passed (Fig. 4). This was then drawn proximally by the gastroscope in the colostomy. Once exteriorized through the stoma, the guide wire was attached to the anvil of an EEA circular stapler (size 21)

Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection

Abstract: We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients.

Congenital hypothyroidism associated with congenital diaphragmatic hernia.

Abstract: To the Editor:A female infant was born by normal delivery at full term with birth weight of 2.95 kg. The antenatal period was uneventful except mild polyhydramnios that resolved in repeat scan done after two weeks. Baby was vigorous at birth with Apgar’s of eight and nine at one and five minutes respectively. She developed respiratory distress at four hours of age and chest radiograph revealed left sided diaphragmatic hernia with moderate shift of the mediastinum to the right side (Fig. 1). Subsequently, she was intubated and commenced on mechanical ventilation. She underwent surgical repair of diaphragmatic hernia at 12 h of age. Post-operative recovery was uneventful. Blood taken for newborn screening by heel prick on day 5 of life revealed high thyroid stimulating hormone (TSH) with value 43 mU/L. Subsequent thyroid function tests (TFT) revealed total T4 and TSH levels as 8 mcg/dL and 51 mU/L respectively. Ultrasound of the neck could not localise thyroid gland. One hundred twenty-three Iodine Radionuclide thyroid scan performed on day eight of life showed zero uptake at neck. She was commenced on thyroxin supplement immediately. Free T4 and TSH levels normalised after 3 wk of commencement of therapy. Cytogenetic study revealed normal female karyotype and DNA microarray did not reveal any genetic mutation. Congenital hypothyroidism (CH) is the most common cause of preventable intellectual disability in pediatric population. Its incidence has been cited around 1:4000 in several studies [1]. CH has been associated with various congenital malformations with cardiac being the most common [2]. Associations of CH, mainly of syndromic varieties, have also been sought with various renal, urologic, skeletal, gastrointestinal, and neurological (ataxia) abnormalities [3–5]. Though neonatal respiratory distress has been ascribed as an association of congenital hypothyroidism by Doyle et al., our extensive literature search could not reveal any case or incidence of Congenital diaphragmatic hernia (CDH) associated with congenital hypothyroidism, though umbilical hernia is a commonly reported finding in CH. Few genetic