Near‐infrared spectroscopy for monitoring muscle oxygenation

Near‐infrared spectroscopy (NIRS) is a non‐invasive method for monitoring oxygen availability and utilization by the tissues. In intact skeletal muscle, NIRS allows semi‐quantitative measurements of haemoglobin plus myoglobin oxygenation (tissue O₂ stores) and the haemoglobin volume. Specialized algorithms allow assessment of the oxidation–reduction (redox) state of the copper moiety (CuA) of mitochondrial cytochrome c oxidase and, with the use of specific tracers, accurate assessment of regional blood flow. NIRS has demonstrated utility for monitoring changes in muscle oxygenation and blood flow during submaximal and maximal exercise and under pathophysiological conditions including cardiovascular disease and sepsis. During work, the extent to which skeletal muscles deoxygenate varies according to the type of muscle, type of exercise and blood flow response. In some instances, a strong concordance is demonstrated between the fall in O₂ stores with incremental work and a decrease in CuA oxidation state. Under some pathological conditions, however, the changes in O₂ stores and redox state may diverge substantially.     

Overweight and obesity among patients attending a Nigerian oral surgery clinic: implications for oral surgical practice in Nigeria

Aim

To determine the prevalence of overweight and obesity among patients attending oral and maxillofacial outpatient clinic of the Lagos University Teaching Hospital, Nigeria; and discuss the clinical and surgical implications that obesity has on the delivery of oral and maxillofacial surgical and anaesthetic care.

Methods

Consecutive patients presenting to the oral and maxillofacial surgery outpatient clinic at the Lagos University Teaching Hospital, Nigeria over a 4-month period (May–August 2004) were screened for age, sex, height and weight. All of the patients were treated for dentoalveolar surgical procedures (routine and surgical extractions), incisional and excisional biopsies, and enucleation under local anaesthesia.

Results

The BMIs of the studied patients ranged from 16.7 to 39.8 kg/m², with a mean of 24.6 ± 4.5 kg/m². Prevalence of excess weight was 39.1%. Thirty-one (11.4%) patients were obese and 75 (27.7%) patients were overweight. A significant difference was observed in the BMIs of male and female patients (P=0.000). The age groups < 30 years had mean BMIs that were considered normal; whereas other age groups above 30 years had mean BMIs that were considered overweight. Prevalence of obesity increases with increasing age. Obese individuals were seen in all the age groups except those < 20 years.

Conculsions

The prevalence of excess weight (overweight and obesity) in patients presenting in the studied oral and maxillofacial outpatient setting was 39.1%. Oral and maxillofacial surgeon needs to be aware of obesity-/overweight-related medical and surgical issues and take them into consideration when treating these patients.     

Novel TMPRSS6 mutations associated with iron‐refractory iron deficiency anemia (IRIDA)

Mutations leading to abrogation of matriptase‐2 proteolytic activity in humans are associated with an iron‐refractory iron deficiency anemia (IRIDA) due to elevated hepcidin levels. In this paper we describe 12 IRIDA patients belonging to 7 unrelated families and identify 10 (9 novel) TMPRSS6 mutations spread along the gene sequence: 5 missense, 1 non sense and 4 frameshift. The frameshift and non sense mutations are predict to result in truncated protein lacking the catalytic domain. The causal role of missense mutations (Y141C, I212T, R271Q, S304L and C510S) is demonstrated by in silico analysis, their absence in 100 control chromosomes and the high conservation of the involved residues. The C510S mutation in the LDLRA domain in silico model causes an intra‐molecular structural imbalance that impairs matriptase‐2 activation. We also assessed the in vitro effect on hepcidin promoter and the proteolytic activity of I212T and R271Q variants demonstrating a reduced inhibitory effect for the former mutation, but surprisingly a normal function for R271Q which appears a silent mutation in vitro. Based on mRNA expression studies I212T could also decrease the total amount of protein produced, likely interfering with mRNA stability. Collectively, our results extend the pattern of TMPRSS6 mutations associated with IRIDA and propose a model of causality for some of the novel missense mutation. © 2010 Wiley‐Liss, Inc.     

MEN1 family with a novel frameshift mutation

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.     

Effects of Tobacco Smoking on the Dorsum of the Tongue and Buccal Epithelium

Objective: The aim of this study was to assess the effects of tobacco smoking on the dorsum of the tongue and buccal epithelium. Methodology: This case control cross-sectional study was conducted with 174 smoking and non-smoking volunteers living in the city of Hail, Northern KSA. Cytological Materials were obtained from buccal mucosa and dorsum of the tongue, and assessed using cytopathological methods. Results: In buccal smears, cytological atypia was observed in 17 out of 101 (16.8%) smoker cases but only 3/73(4.1%) of the controls. For cytological atypia in buccal and tongue smears, the adjusted odd ratio (OR) and the 95% confidence interval (CI) were found to be 4.7 (1.3-16.8), P < 0.016)) and 4.3 (0.93- 20.2), P <0.06)), respectively, in the two sites. Conclusion: Tobacco smoking is a major risk factor for occurrence of cytological atypia, which might subsequently develop into oral precancerous and cancerous lesions. Oral exfoliative cytology is an easy and cheap non-invasive procedure which appears highly suitable for screening populations at risk of developing oral cancer.     

Pelvic radiation therapy: Between delight and disaster

In the last few decades radiotherapy was established as one of the best and most widely used treatmentmodalities for certain tumours. Unfortunately that came with a price. As more people with cancer survive longer an ever increasing number of patients are living with the complications of radiotherapy and have become, in certain cases, difficult to manage. Pelvic radiation disease(PRD) can result from ionising radiationinduced damage to surrounding non-cancerous tissues resulting in disruption of normal physiological functions and symptoms such as diarrhoea, tenesmus, incontinence and rectal bleeding. The burden of PRDrelated symptoms, which impact on a patient's quality of life, has been under appreciated and sub-optimally managed. This article serves to promote awareness of PRD and the vast potential there is to improve current service provision and research activities.     

Targeted inhibition of the serotonin 5HT2A receptor improves coronary patency in an in vivo model of recurrent thrombosis

Summary. Background: Release of serotonin and activation of serotonin 5HT_2A receptors on platelet surfaces is a potent augmentative stimulus for platelet aggregation. However, earlier‐generation serotonin receptor antagonists were not successfully exploited as antiplatelet agents, possibly owing to their lack of specificity for the 5HT_2A receptor subtype. Objective: To assess whether targeted inhibition of the serotonin 5HT_2A receptor attenuates recurrent thrombosis and improves coronary patency in an in vivo canine model mimicking unstable angina. Methods: In protocol 1, anesthetized dogs were pretreated with a novel, selective inverse agonist of the 5HT_2A receptor (APD791) or saline. Recurrent coronary thrombosis was then initiated by coronary artery injury + stenosis, and coronary patency was monitored for 3 h. Protocol 2 was similar, except that: (i) treatment with APD791 or saline was begun 1 h after the onset of recurrent thrombosis; (ii) template bleeding time was measured; and (iii) blood samples were obtained for in vitro flow cytometric assessment of platelet responsiveness to serotonin. Results: APD791 attenuated recurrent thrombosis, irrespective of the time of treatment: in both protocols, flow–time area (index of coronary patency; normalized to baseline coronary flow) averaged 58–59% (P < 0.01) following administration of APD791 vs. 21–28% in saline controls. Moreover, the in vivo antithrombotic effect of APD791 was not accompanied by increased bleeding, but was associated with significant and selective inhibition of serotonin‐mediated platelet activation. Conclusion: 5HT_2A receptor inhibition with APD791, even when initiated after the onset of recurrent thrombosis, improves coronary patency in the in vivo canine model.