Analysis of drug action on tumor cell metabolism using electronic sensor chips

Chemotherapeutic drugs affect the metabolism of tumor cells regardless of the specific target of action. Basic parameters of cell metabolism are extrusion of acids into the microenvironment and oxygen consumption. To analyze these changes on living cells in real-time, a test system based on multiparametric chips with an array of sensors for monitoring pH and O(2) as well as electric impedance has been developed. Cells are cultivated on these chips and supplied with medium by a fluid perfusion set-up which mimics microphysiological conditions and allows for drug addition and removal. Human colon carcinoma cells LS174T were used as a model to test the effect of drugs. Cells growing on chips were monitored for 24 h and longer. Untreated cells showed a continuous increase in the rate of acidification, while the rate of respiration remained fairly constant. Addition of chloroacetaldehyde (50 microM) rapidly attenuated O(2) consumption with a gradual decrease in acidification following. In contrast, with cisplatin (16.7 microM) a delayed and gradual decrease in both the rates of acidification and respiration effect occurred over 2-3 days. These results provide insights to the mechanisms of action of these drugs, which are coherent with those already known. Thus, multiparametric sensor chips provide elementary information on drug action.     

Periodontal disease in children with Down's syndrome

Abstract – The occurrence of supra- and subgingival calculus, gingival inflammation, periodontal pockets ( 5 mm) and alveolar bone loss was determined in children (10-19 yr) with Down's syndrome (D-S) and in an aged- and sex-matched control group ( n = 39). Of D-S children ( n = 71), 39 of the patients (mean age 15.5 yr) cooperated in a clinical and roentgenologic examination. Alveolar bone loss was determined around incisors and first molars on intraoral radiographs when the distance between cementoenamel junction (GEJ) to alveolar crest (AC) exceeded 2.0 mm. Alveolar bone loss was diagnosed in 39% of the D-S children compared to 3% in the control group ( P <0.001). Of the total number of sites examined on radiographs the distance from CEJ to AC exceeded 2.0 mm in 8% in the D-S group compared to 0.2% in the control group ( P <0.001). The frequency of sites with alveolar bone loss in D-S children was significantly ( P <0.001) higher around the mandibular incisors compared to first molars. The study shows that early signs of periodontitis are frequently seen in D-S children as early as 11 yr of age and the lesions are first diagnosed in the mandibular anterior region.     

Thrombosis at venous insertion sites after inferior vena caval filter placement

Color Doppler flow imaging or compression ultrasound (US) was used to prospectively determine frequency of thrombosis at 54 venous insertion sites (47 in common femoral veins, seven in right internal jugular veins) after percutaneous placement of Greenfield filters for interruption of the inferior vena cava. Fifty-one filters were successfully placed in 51 patients with a dilator set or a balloon angioplasty catheter. Nine focal thrombi were detected in the common femoral vein (19%) and one in the right internal jugular vein (14%). Use of dilators induced eight thrombi (24%), compared with two (10%) from balloon catheters. The left common femoral vein had a high frequency of thrombosis, regardless of dilation technique (five of nine). Of nine patients with acute common femoral vein thrombosis, four became symptomatic within 10 days after the procedure. Patients may remain asymptomatic or have delayed symptoms; thus, US is valuable for determining patients at risk of thrombosis of the common femoral vein.     

Myocardial tagging in polar coordinates with use of striped tags

Regional deformation abnormalities in the heart wall provide a good indicator of ischemia. Myocardial tagging with magnetic resonance imaging is a new method of assessing heart wall motion during contraction. Current methods of myocardial tagging either do not provide two-dimensional information or lack a coordinate system well adapted to the morphology of the heart. In this article, the authors describe a new tagging method that provides a true polar coordinate system, with both radial and angular dimensions. This is accomplished with use of a section-selective version of spatially modulated magnetization resulting in striped tags (STAGs). These STAG planes are placed in the myocardium in a star pattern so that they intersect on the long axis of the heart and stripes appear through the width of the heart wall. In the short-axis view during contraction, rotation around the long axis yields angular information such as shear and twist, while separation of the stripes within the myocardium permits measurement of radial thickening. Therefore, this method provides a coordinate system for calculating two-dimensional strain that is adapted to the morphology of the left ventricle.     

Presence of residual basal cell carcinoma in re-excised specimens is more probable when deep and lateral margins were positive

In order to quantify presence of residual BCC in patients with histologic positive margins after the first excison and to correlate the presence of residual tumor in re‐excised lesions with the location of the positive margin on the first excision, a retrospective evaluation of 2053 surgically treated BCC was performed. Only 38.3% of the re‐excised lesions showed residual tumor. In the group of re‐excised lesions where residual BCC was found, 13% had lateral positive margin in the first excision, 39% had deep positive margin and 48% had both lateral and deep positive margins. In the group of re‐excised lesions where no residual BCC was found, 49% of the primary excised lesions had lateral positive margin, 32% had deep positive margin and 19% had both deep and lateral positive margins. The association between residual tumor and positive margins was statistically significant (p = 0.01). Our findings confirm that presence of residual tumour is more likely when both lateral and deep margins are compromised.     

Effect of disease severity and pharmacotherapy of asthma on oral health in asthmatic children

Abstract – Oral health was studied in a group of asthmatic children (n = 61). The children were divided in two groups, 5–10 and 11–18 yr of age. The individuals with asthma were further sub grouped with respect to the disease severity. Severe asthma was defined as more than 10 asthmatic attacks per year. This patient group had daily medication compared to children with moderate asthma (<10 asthmatic attacks/yr) who medicated temporarily. 55 age matched children from the same area made up the control group. Ail children were examined clinically and two bitewing radiographs were taken. The results showed no statistically significant differences concerning caries prevalence and gingival condition in asthmatic children compared to a healthy control group. The study shows that neither the asthma per se nor the disease severity affected the caries prevalence and gingival condition in asthmatic children.     

Craniofacial growth in bone marrow transplant recipients treated with growth hormone after total body irradiation

Abstract— The effect of growth hormone (GH) treatment on craniofacial development was studied in five children exhibiting growth retardation following bone marrow transplantation. Linear and angular measurements were made on lateral radiographic cephalograms taken prior to the start of GH treatment and after an average treatment time of 1.2 yr. The results showed that the mean growth increments of mandibular length in the GH treated children, exceeded the corresponding values of the control group by 150% during the period of investigation. It is suggested that this dimensional increase in the patients was due to GH stimulation on the chondral growth process in the mandibular condyles.     

Influence of phenytoin on cytoplasmic free Ca2+ level in human gingival fibroblasts

Abstract— Influence of 5,5-diphenylhydantoin (phenytoin;PHT) on the cytoplasmic free Ca²⁺ concentration, [Ca²⁺]ⁱ, was studied in fura 2 loaded adherent monolayers of human gingival fibroblasts derived from three patients before and after 9 months of PHT therapy. In the patient where gingival overgrowth developed during PHT medication (responder), addition of PHT to gingival fibroblasts derived before PHT medication induced a transient extracellular Ca²⁺ dependent increase in [Ca²⁺]ⁱ. In a non-responder patient, where gingival overgrowth did not develop during the same period of PHT therapy, addition of PHT to gingival fibroblasts derived before the start of medication did not significantly affect [Ca²⁺]_i. Under extracellular Ca²⁺ deficient conditions, addition of PHT to serum-starved fibroblasts derived from the two categories of patients before the medication resulted in an increase in [Ca²⁺]_i. In fibroblasts derived from the responder patient during PHT medication, in contrast to those from the non-responders (n = 2), the basal level of [Ca²⁺]_i was significantly decreased. The results indicate that, in the cases studied, there is a relationship between PHT induced alterations in [Ca²⁺]_i in gingival fibroblasts and the clinical development of gingival overgrowth.     

Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting.