Automated landmark identification on cone-beam computed tomography: Accuracy and reliability.

OBJECTIVES: To evaluate the accuracy and reliability of a fully automated landmark identification (ALI) system as a tool for automatic landmark location compared with human judges. MATERIALS AND METHODS: A total of 100 cone-beam computed tomography (CBCT) images were collected. After the calibration procedure, two human judges identified 53 landmarks in the x, y, and z coordinate planes on CBCTs using Checkpoint Software (Stratovan Corporation, Davis, Calif). The ground truth was created by averaging landmark coordinates identified by two human judges for each landmark. To evaluate the accuracy of ALI, the mean absolute error (mm) at the x, y, and z coordinates and mean error distance (mm) between the human landmark identification and the ALI were determined, and a successful detection rate was calculated. RESULTS: Overall, the ALI system was as successful at landmarking as the human judges. The ALI's mean absolute error for all coordinates was 1.57 mm on average. Across all three coordinate planes, 94% of the landmarks had a mean absolute error of less than 3 mm. The mean error distance for all 53 landmarks was 3.19 ± 2.6 mm. When applied to 53 landmarks on 100 CBCTs, the ALI system showed a 75% success rate in detecting landmarks within a 4-mm error distance range. CONCLUSIONS: Overall, ALI showed clinically acceptable mean error distances except for a few landmarks. The ALI was more precise than humans when identifying landmarks on the same image at different times. This study demonstrates the promise of ALI in aiding orthodontists with landmark identifications on CBCTs.

Diuretics: a review.

Diuretics, in one form or another, have been around for centuries and this review sets out to chart their development and clinical use. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. The different classes of diuretics are characterized, along with their mode of action. The clinical use of diuretics in conditions like congestive cardiac failure and hypertension, as well as some rarer, but clinically important, conditions is then examined. An account is given of the adverse effects of diuretics and how they come about. Common adverse effects like hypokalaemia and hyponatraemia are examined in some detail, and other electrolyte disturbances like hypomagnesaemia also gain a mention. Diuretic use in chronic kidney disease is examined and new guidelines that have been introduced are presented. A section on diuretic abuse is included as this is becoming an all too common clinical scenario, and the sometimes tragic consequences of this abuse are emphasized. Diuretics also find a role in the diagnosis of forms of renal tubular acidosis and this role is explored. Finally, a selection of some of the newer approaches to diuretic therapy are presented, often the consequence of the increasing development of molecular biology, and some of the novel compounds - which may be in drug formularies of the future - are revealed.

Characteristics and mortality of severe hyponatraemia--a hospital-based study.

OBJECTIVE: To determine the characteristics, causes and outcome of severe hyponatraemia (< 125 mmol/l) in hospitalized patients, and to identify mortality predictors. DESIGN: Prospective case controlled study of sequentially presenting patients with a serum sodium (Na) < 125 mmol/l. PATIENTS AND METHODS: One hundred and four hyponatraemic and 104 randomly chosen normonatraemic (Na > 135 mmol/l) adult patients were studied. We measured hospital mortality and days in hospital, diagnoses, drug history and cause of hyponatraemia. Na was recorded at admission, as well as the closest level measured before death or discharge. In addition, the lowest Na was recorded (if this was not at admission). RESULTS: Hyponatraemic patients were older (mean age +/- 1 SD 69 +/- 14 years) than controls (61 +/- 16 years, P < 0.001), but of similar sex ratio. On admission, Na in the hyponatraemic group was 125 +/- 7 mmol/l compared with 139 +/- 3 mmol/l in controls (P < 0.0001), but fell to 120 +/- 4 mmol/l before rising at discharge to 131 +/- 7 mmol/l (all changes P < 0.001). Overall mortality was 27% in hyponatraemic patients compared with 9% in controls (P = 0.009), and length of admission was also greater (16 +/- 12 vs. 13 +/- 11 days, P < 0.005). Mortality was greater in patients whose Na levels fell during admission (34%vs. 16%, P < 0.05), and these patients appeared to have an excess of diuretic-induced and possibly iatrogenic hyponatraemia. CONCLUSIONS: Severe hyponatraemia in hospital patients is associated with prolonged admissions and significantly increased mortality compared with normonatraemic patients. A particular group at high risk of death are those whose Na levels fall after admission. They may represent a 'sicker' group, and deserve increased monitoring and surveillance.

Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia.

Typically, autosomal dominant familial hypercholesterolaemia (FH) is caused by mutations in the low density lipoprotein (LDL) receptor or apolipoprotein B genes that result in defective clearance of plasma LDL by the liver, but a third gene (PCSK9), encoding a putative proprotein convertase, has recently been implicated. Two independent microarray studies support a role for PCSK9 in sterol metabolism and adenoviral-mediated over-expression of PCSK9 in mouse liver depletes hepatic LDL-receptor protein, but the mechanism by which dominant mutations cause human FH is unclear. We have identified the D374Y mutant of PCSK9 in three FH families of English origin; all 12 affected individuals have unusually severe hypercholesterolaemia and require more stringent treatment than typical FH patients, who are heterozygous for defects in the LDL receptor. We have stably expressed wild-type (WT) and variant PCSK9 in McArdle-7777 rat hepatoma cells and shown by confocal microscopy that all forms of PCSK9 co-localize with protein disulphide isomerase in the ER whether or not they can be autocleaved. Expression of the proposed pathogenic variants, but not of WT, S386A or F216L PCSK9, increases secretion of apolipoprotein B100-containing lipoproteins from the cells by 2-4-fold probably by reducing the degradation of nascent protein; no differences in LDL-receptor content were observed in cells expressing WT, S386A or F216L PCSK9 and only a small reduction in cells expressing the D374Y or S127R mutants. This suggests that the variants of PCSK9 found in FH influence the secretion of apoB-containing lipoproteins, providing an explanation for the marked increase in circulating LDL in heterozygous carriers.

An accurate and portable system for glycated haemoglobin measurement in the tropics.

Measurement of glycated haemoglobin (HbA1c) is vital to provide meaningful diabetic care, but the assay is difficult and expensive, making its availability limited in resource-poor countries. We have field-tested a novel near-patient HbA1c meter (Glycosal; Provalis Diagnostics Ltd, UK) in northern Ethiopia. The machine was easy to use and gave results which correlated well (r = -0.96) with standard laboratory methods. The meter also performed well and retained accuracy at high ambient temperature (34.0 degrees C). Though still relatively expensive (pound 4 per test), this meter does give the opportunity for practical and appropriate HbA1c testing in tropical climes, and should be considered for at least intermittent use in diabetic patients.