Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines

BackgroundBi-allelic germline mutations of one of the DNA mismatch repair genes, so far predominantly found in PMS2, cause constitutional MMR-deficiency syndrome. This rare disorder is characterised by paediatric intestinal cancer and other malignancies. We report the clinical, immunohistochemical and genetic characterisation of four families with bi-allelic germline PMS2 mutations. We present an overview of the published gastrointestinal manifestations of CMMR-D syndrome and propose recommendations for gastro-intestinal screening.Methods and ResultsThe first proband developed a cerebral angiosarcoma at age 2 and two colorectal adenomas at age 7. Genetic testing identified a complete PMS2 gene deletion and a frameshift c.736_741delinsTGTGTGTGAAG (p.Pro246CysfsX3) mutation. In the second family, both the proband and her brother had multiple intestinal adenomas, initially wrongly diagnosed as familial adenomatous polyposis. A splice site c.2174+1G>A, and a missense c.137G>T (p.Ser46Ile) mutation in PMS2 were identified. The third patient was diagnosed with multiple colorectal adenomas at age 11; he developed a high-grade dysplastic colorectal adenocarcinoma at age 21. Two intragenic PMS2 deletions were found. The fourth proband developed a cerebral anaplastic ganglioma at age 9 and a high-grade colerectal dysplastic adenoma at age 10 and carries a homozygous c.2174+1G>A mutation.Tumours of all patients showed microsatellite instability and/or loss of PMS2 expression.ConclusionsOur findings show the association between bi-allelic germline PMS2 mutations and severe childhood-onset gastrointestinal manifestations, and support the notion that patients with early-onset gastrointestinal adenomas and cancer should be investigated for CMMR-D syndrome. We recommend yearly follow-up with colonoscopy from age 6 and simultaneous video-capsule small bowel enteroscopy from age 8.     

In vitro evaluation of the permeation through reconstructed human epidermis of essentials oils from cosmetic formulations

The permeation of essential oils through SkinEthic^® reconstructed human epidermis, (RHE), was studied in vitro to establish a convenient tool to monitor the kinetics of release of active principles from cosmetic formulations. Twelve days old human epidermis held on polycarbonate disks was revitalized by addition of growth medium and incubated at 37 °C in 5% CO₂ atmosphere for five days prior to investigation. A system of six custom designed glass Franz-type diffusion cells were used for the permeation studies at 34 °C. The diffusion kinetic for 8 selected terpenes (camphor, carvone, 1,8-cineole, linalool, menthol, α-thujone, menthone, t-anethole), chosen as analytical markers of a mixture of plant essential oils contained in a cosmetic formulation, was probed by HS/SPME–GC–MS analysis and elaborated according to Fick's first law to obtain skin permeability coefficients (P_S = 1.51, 1.47, 1.36, 0.80, 0.62, 0.40 and 0.14 × 10⁻³ cm/h, respectively). The method proved to be sensitive, simple and reproducible, and RHE represents a convenient model for safety/quality assessment of cosmetic formulations.     

Thoracic epidural analgesia and the cardiovascular system

Thoracic epidural exerts a remarkable influence on the cardiovascular system (Table 1). With regard to cardiac electrical activity in animal models, TEA was found to lengthen repolarization and to protract the refractory period more at the ventricular site than at the atrium. The atrio-ventricular conduction and refractoriness are also prolonged. Human studies documented a slight impairment in the sensitivity of the baroreflexes sparing the sympathetically mediated responses to various stress if TEA is limited to the first five thoracic vertebrae. Although an overall reduced risk of perioperative dysrhythmias, TEA is not shown to decrease the incidence of postoperative atrial fibrillation.There are contradictory results from animal studies on the effect of TEA on ventricular function. In healthy patients, TEA seems to alter left ventricular contractility and reduce cardiac output, whereas in cardiac surgical patients, the left ventricular global and regional wall motion were better preserved.In a canine model, TEA improves regional blood flow by favoring the endocardium. In patients, TEA has been associated with a reduction of the major determinants of cardiac oxygen consumption without jeopardizing coronary perfusion pressure and even increasing the diameter of stenotic coronary segments. Thus, TEA lessens the severity of experimental acute myocardial ischemic injury and quickens the recovery after brief ischemic insult. In patients, changes in clinical markers of ischemic damage, such as Troponin T and Atrial Natriuretic Peptide, are not consistent, except for Brain Natriuretic Peptide, which is diminished. The overall incidence of myocardial infarction is also reduced.TEA produces functional hypovolemia by inhibiting the vasoconstrictor sympathetic outflow, oreover it interferes with the integrity of renin–angiotensin system, but increments vasopressin plasma concentration. Although TEA causes hypotension, it has a beneficial outcome during hemorrhagic shock.     

Evaluation of cuffed tracheal tube size predicted using the Khine formula in children

BACKGROUND: The correct size of cuffed endotracheal tube (CET) limits the risk of postintubation tracheal damage. The aim of this study was to compare the size of the CET used in children with the size predicted by the Khine formula [age (years)/4 + 3]. METHODS: After ethical committee approval, 204 children aged 1 day-15 years were included prospectively in the study. The choice of the size of the CET was made at the discretion of the attending anesthesiologist. The main criterion of judgment was the comparison of the leak before and after inflating the cuff at a pressure of 20 cm.H(2)O. Demographic data, tracheal tube size used and that predicted by Khine's formulae and side-effects were recorded. RESULTS: Overall, 21% of the CET were in accordance with the size predicted by the Khine formula. In the remaining patients, 72% were oversized and 7% undersized. In 12 cases, the size of CET chosen initially was modified: for a larger size in eight children and for a smaller size in four others. Six children (2.9%) presented with minor postoperative complications. CONCLUSIONS: Our data suggest that Khine's formula for predicting the appropriate tracheal tube size underestimates optimal size by 0.5 mm. We therefore recommend the use of the following formula: internal diameter of the CET = [age/4 + 3.5] in children >1 year of age which may be applied without increased risk of complications. The rate of tracheal reintubation as well as the detected leaks supports these recommendations.     

Correlation between pre-operative metabolic syndrome and persistent blood glucose elevation during cardiac surgery in non-diabetic patients

Background: Cardiopulmonary-bypass (CPB) induces hyperglycemia. There is growing evidence that perioperative maintenance of blood glucose within the physiological range improves patients' outcome. Nevertheless, perioperative normoglycemia is often difficult to achieve during surgery with CPB and the response to insulin infusion is characterized by a considerable variability. The aim of this study was to determine to what extent the presence of pre-operative metabolic syndrome (MS) influences the blood glucose and insulin response during cardiac surgery.
Methods: Forty-five patients scheduled for elective cardiac surgery were screened for the presence of MS according to the International Diabetes Federation definition. Patients were then assigned to two groups: those with metabolic syndrome (MSP) and those without (control). During surgery, blood glucose levels were measured in all patients and hyperglycemia was treated with a standard protocol of continuous insulin infusion.
Results: The mean blood glucose levels during CPB increased only in the MSP group ( P <0.001). Mean blood glucose in control patients did not increase during CPB ( P =0.4). Patients with MS received 13.3±8.4 IU of insulin during CPB, while the control group did not require insulin treatment ( P <0.001). Forty percent of patients in the control group and 100% of those in the MSP group developed post-operative insulin resistance. C-reactive protein was higher in the MSP group before, during and at 48 h after surgery.
Conclusions: The mean blood glucose levels during CPB increased only in patients with MS, while they remained unchanged in patients in the control group.     

Benign paroxysmal vertigo of childhood

Benign paroxysmal vertigo of childhood (BPV) is a paroxysmal, non-epileptic, recurrent event characterized by subjective or objective vertigo that occurs in neurologically intact children. We recorded the history and the clinical aspects of 19 cases presenting with neurological problems to the outpatient clinic at the Pediatrics Department of Padova University between 1987 and 1998 and re-examined in 1999. Details were collected on the characteristics of their vertigo: age at onset, mode of onset, trigger factors, duration, frequency and recurrence of episodes, duration of symptoms in time and age at disappearance. An attempt was also made to establish any family history of migraine and kinetosis and the most important data were compared, when possible, with those reported in the literature. Differential diagnosis and pathogenetic hypothesis were also reported. It is worth emphasizing that it is important for pediatricians to be aware of these benign events to ensure a correct diagnostic approach, avoiding the child and family any pointless anxiety or costly and sometimes invasive diagnostic procedures.     

Preoperative assessment of melanoma thickness by ABCD score of dermatoscopy

BACKGROUND: Epiluminescence microscopy is a useful tool for the noninvasive diagnosis of malignant melanoma based on criteria that have been correlated with specific histologic characteristics. Previous studies have also shown a good correlation between the frequency of some dermatoscopic criteria based on pattern analysis (pigment network, blue-gray areas, vascular pattern) and tumor thickness. This technique could be useful in the preoperative assessment of tumor thickness as an indication for sentinel node biopsy. OBJECTIVE: Our purpose was to evaluate the possible role of the total dermatoscopy score (TDS) assigned to a series of lesions in accordance with the ABCD rule of dermatoscopy as a preoperative predictor of melanoma thickness. METHODS: For 84 cutaneous melanomas (17 were in situ melanomas; 67 invasive cases with mean thickness 0. 93 mm; range, 0.2-3.9 mm; standard deviation, 0.63) consecutively excised at the Department of Dermatology of Florence, TDS was established by two observers blinded as to the tumor thickness. The performance of different cut-off points of TDS in the diagnosis of melanoma with Breslow's thickness more than 0.75 or 1.00 mm was investigated by receiver operating characteristic (ROC) analysis. Accuracy of classification was evaluated in terms of sensitivity, specificity, and area under ROC curves (AUC). RESULTS: The TDS assigned to cutaneous melanomas by the ABCD rule increased with the thickness of the lesions from in situ melanomas to melanomas of intermediate thickness (0.75-1.50 mm). As a preoperative method for the detection of melanomas with a Breslow thickness greater than 0. 75 mm, a TDS cut-off point of 6.80 showed 80% sensitivity, 84% specificity, and 82% diagnostic accuracy (AUC value, 0.90). TDS performed better in the diagnosis of a thickness threshold of 0.75 than 1.00 mm (higher AUC value). CONCLUSION: The TDS calculated by the ABCD rule of dermatoscopy-a simplified approach to dermatoscopic diagnosis of melanoma-provides useful information for the preoperative assessment of melanoma thickness greater than 0.75 mm.