Risk factors for suicide in epilepsy: a case control study

PURPOSE: Suicide is considered to be one of the most important causes of death contributing to the increased mortality of persons with epilepsy. We investigated the association between the risk of suicide in persons with epilepsy and clinical factors that might increase or have been suggested to increase the risk of suicide. METHODS: A case-control study was nested within a cohort of 6,880 patients registered in the Stockholm County In-Patient Register with a diagnosis of epilepsy. The study population was followed up through the National Cause of Death Register. Twenty-six cases of suicide, 23 cases of suspected but not proven suicide, and 171 controls, living epilepsy patients, were selected from the cohort. Clinical data were collected through medical record review. RESULTS: There was a ninefold increase in risk of suicide with mental illness and a 10-fold increase in relative risk (RR) with the use of antipsychotic drugs. The estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4-58.3] for onset of epilepsy at younger than 18 years, compared with onset after 29 years. The risk of suicide seemed to increase with high seizure frequency and antiepileptic drug (AED) polytherapy, although the estimates were imprecise and the associations not statistically significant. Insufficient data on seizure frequency and changes in AED dosage due to incomplete case records were associated with high RRs. We found no association between risk of suicide and any particular AED, with type of epilepsy, or localization or lateralization of epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1-1.7)]. CONCLUSIONS: The profile of the epilepsy patient who commits suicide that emerges from our study is a patient with early onset (particularly onset during adolescence) but not necessarily severe epilepsy, psychiatric illness, and perhaps inadequate neurologic follow-up. Previous reports of an association with temporal lobe epilepsy could not be confirmed.     

Temporal effects of cell adhesion on mechanical characteristics of the single chondrocyte.

Cell adhesion to material surfaces is a fundamental phenomenon in tissue response to implanted devices, and an important consideration in tissue engineering. For example, elucidation of phenomena associated with adhesion of chondrocytes to biomaterials is critical in addressing the difficult problem of articular cartilage regeneration. The first objective of this study was to measure the mechanical adhesiveness characteristics of individual rabbit articular chondrocytes as a function of seeding time to provide further understanding of the cell adhesion process. The second objective was to quantify the force required to separate the plasma membrane from the underlying cytoskeleton as a function of seeding time. After culturing chondrocytes on glass coverslips for 1, 2, 4, 6 h, two biomechanical tests were performed on single chondrocytes: (i) mechanical adhesiveness measurement by the cytodetacher; and (ii) plasma membrane tether formation force measurement by optical tweezers. Cell mechanical adhesiveness increased from 231+/-149 Pa at 1 h to 1085+/-211 Pa at 6 h. The cell contact area with the substrata increased from 161+/-52 microm(2) at 1 h to 369+/-105 microm(2) at 6 h. The tether formation force increased from 232+/-23 pN at 1 h to 591+/-17 pN at 6 h. Moreover, fluorescence staining by rhodamine-phalloidin demonstrated the process of actin spreading within the cytoskeleton from 0.5 to 6 h and allowed for measurement of cell height which was found to decrease from 12.3+/-2.9 microm at 0.5 h to 6.2+/-0.9 microm at 6 h.     

Autofluorescence characterization for the early diagnosis of neoplastic changes in DMBA/TPA-induced mouse skin carcinogenesis

BACKGROUND AND OBJECTIVE: Squamous cell carcinoma (SCC), the second most common skin cancer, usually remains confined to the epidermis for some time but eventually penetrates the underlying tissues, if left untreated. The non-invasive early detection of the SCC is important for appropriate therapeutic strategies. In this study, we aim to characterize the tissue transformation in DMBA/TPA induced mouse skin tumor model using autofluorescence excitation emission matrix (EEM) in conjunction with a multivariate statistical method for early detection of the neoplastic changes. STUDY DESIGN/MATERIALS AND METHODS: The fluorescence EEM from experimental group (n = 40; DMBA/TPA application), control group (n = 6; acetone application), and the blank group (n = 6; no application of DMBA/TPA or acetone) were measured every week using a spectrofluorometer coupled with a fiber optic bundle. The EEM was recorded at excitation wavelengths from 280 to 460 nm at 10 nm intervals and the fluorescence emission was scanned from 300 to 750 nm. The fluorescence emission characteristics corresponding to different fluorophores were extracted from the EEM and the spectral data were used in a multiple/linear discriminant statistical algorithm. RESULTS: The changes in the fluorescence emission intensity were observed as early as the 1st week of tumor initiation by DMBA. Morphological changes as well as differences in the gross appearance of the skin surface were observed during the entire tumor initiation and promotion period of 15 weeks. The statistical analysis was performed for each excitation wavelength in the EEM and better classification accuracy was obtained for 280 and 410 nm excitations, corresponding to tryptophan and endogenous porphyrins, respectively. The statistical analysis of the combination wavelengths resulted in 11.6% increase in the overall classification accuracy when compared to the highest classification accuracy obtained with single wavelength analysis. CONCLUSION: The intensity ratio mapping using the combination of emission intensities of key fluorophores such as tryptophan, collagen, NADH, and endogenous porphyrins from the measured EEM in conjunction with a simple multivariate statistical analysis can be used as a potential tool for the discrimination of early neoplastic changes with improved classification accuracy. Tryptophan and endogenous porphyrins may be used as biomarkers for the discrimination of early neoplastic changes when single wavelength excitations are used.     

Comparison of 585 and 595 nm laser-induced vascular response of normal in vivo human skin

BACKGROUND AND OBJECTIVES: Two wavelengths, 585 and 595 nm, are currently common options for treating vascular malformations such as port-wine stains (PWS). Controversy exists as to which wavelength induces greater photothermal damage to the blood vessels and subsequent resolution of the malformations. STUDY DESIGN/MATERIALS AND METHODS: We irradiated normal, human skin in vivo at 585 and 595 nm wavelengths using fluences of 10-30 J/cm(2) with a 1.5 millisecond laser pulse. The level of purpura, total vascular damage, maximum coagulation depth (MCD), and perivascular damage were quantified by gross observation and histological analysis. RESULTS: Results demonstrated that 585 nm light caused greater purpura, vascular damage, maximum coagulation depth, and perivascular damage than 595 nm. Purpura showed a positive correlation with total vascular damage to a certain extent beyond which the total vascular damage did not change. For equivalent purpura, 585 and 595 nm produced no statistically significant difference in vascular damage. The difference in the laser-induced vascular damage between 585 and 595 nm, although statistically significant, was no more than 50%. CONCLUSIONS: The bathochromic (red) shift and formation of met-hemoglobin, which reduces the 585 nm light absorption and increases that of 595 nm compared to native oxy-hemoglobin, play a considerable role in creating more parity in vascular damage between the two wavelengths than would be expected based on their respective "native" absorption coefficients alone.     

Para-aortic lymph node radiation in advanced cervical cancer

From 1970 until December, 1977, 36 patients with advanced carcinoma of the uterine cervix and with iliac or para-aortic nodes interpreted as un-equivocally positive on lymphangiography have received radiation therapy (4500–5000 rad) to the para-aortic area at the Department of Therapeutic Radiology at Tufts-New England Medical Center Hospital. Of 29 patients who received para-aortic area irradiation as part of their initial treatment, local control was achieved in 18 patients (62%). Of these, 11 patients are currently alive with no evidence of disease (NED); two died without evidence of tumor. The remaining 16 patients died of their tumor (11 with locally uncontrolled tumor and five with distant metastasis). Of seven patients in whom the para-aortic area was treated because of retroperitoneal nodal recurrence, only two are alive without disease and the rest succumbed to their tumor. Overall, four patients developed major complications requiring surgical intervention. Detailed results and our current pre-treatment evaluation policy including lymphangiography, percutaneous needle biopsy and selective extra-peritoneal lymph node biopsy will be discussed.     

Dynamic Measurements of Transverse Optical Trapping Force in Biological Applications

Optical tweezers present a technology for measurements of biological forces in the piconewton range. In such applications, one method of calibrating the transverse optical trapping force involves relating a known external force to the displacement of the trapped object from the trapping center. In this work we used Fourier analysis of the equation of motion to calculate the displacement of the trapped object from the trapping center under an external force induced by viscous drag. Triangular waveforms of different frequencies were used both in theoretical modeling and experiments to induce a force on a trapped object. We investigated the contribution of various factors including frequency of the external force, fluid viscosity, density, and dimensions of the trapped object, stiffness of the optical trap, and frequency response of the instruments used to control the motion of the viscous medium to the accuracy of the calibration. The developed model can be adopted for calibration of the transverse trapping force, analysis of the trapped object motion, and reconstruction of a force profile during measurements of dynamic biological forces.     

Opportunistic screening for diabetes in routine clinical practice

OBJECTIVE: Since 1997, the American Diabetes Association has recommended that nondiabetic individuals >/=45 years of age be screened for diabetes at least every 3 years. We sought to characterize the frequency, methods, and results of diabetes screening in routine clinical practice. RESEARCH DESIGN AND METHODS: We studied opportunistic screening in nondiabetic members of a health maintenance organization >/=45 years of age who were assigned to a large, integrated, academic health care delivery system. Screening was defined as the first glucose, HbA(1c), or oral glucose tolerance test (OGTT) performed between 1 January 1998 and 31 December 2000. Chart review was performed to determine the prevalence of diabetes risk factors and to describe follow-up. RESULTS: Of 8,286 nondiabetic patients >/=45 years of age, 69% (n = 5,752) were screened. The frequency of screening was greater in patients with one or more primary care visits and increased with age. Women were more likely to be screened than men, and patients with at least one diabetes risk factor were more likely to be screened than those without risk factors. Random plasma glucose was the most common screening test (95%). Four percent (n = 202) of those screened had abnormal results. Only 38% (n = 77) of those with abnormal results received appropriate follow-up, and 17% (n = 35) were diagnosed with diabetes within 6 months of screening. The yield of screening was very low (0.6%, 35 of 5,752). CONCLUSIONS: Despite frequent screening and appropriate targeting of high-risk patients, follow-up of patients with abnormal results is uncommon and the yield of screening is low. Interventions are needed to help physicians recognize and provide appropriate follow-up for patients with potentially abnormal random glucose levels.     

Integrating model-based decision support in a multi-modal reasoning system for managing type 1 diabetic patients

We present a multi-modal reasoning (MMR) methodology that integrates case-based reasoning (CBR), rule-based reasoning (RBR) and model-based reasoning (MBR), meant to provide physicians with a reliable decision support tool in the context of type 1 diabetes mellitus management. In particular, we have implemented a decision support system that is able to jointly exploit a probabilistic model of the glucose-insulin system at the steady state, a RBR system for suggestion generation and a CBR system for patient's profiling. The integration of the CBR, RBR and MBR paradigms allows for an optimized exploitation of all the available information, and for the definition of a therapy properly tailored to the patient's needs, overcoming the single approaches limitations. The system has been tested both on simulated and on real patients' data.