Novel expression and regulation of gastrin gene in human ovarian cancer cell line, SW626

Gastrin-secreting tumors have been identified in ectopic locations including the ovary; the mechanisms regulating gastrin gene expression, its distribution, and signaling pathways in these ectopic tissues are not known. The purpose of our present study was to determine: (1) whether the gastrin gene and peptide could be detected in ovarian cancer cell lines, (2) if functional gastrin releasing peptide receptors (GRP-R) are present, and (3) whether gastrin gene expression is altered by GRP. Five ovarian cancer cell lines (SW626, OVCA 420, OVCA 429, OVCA 432, and OVCA 433) were analyzed. We identified gastrin gene and peptide expression in the SW626 cell line but not in the OVCA lines. SW626 cells express a functional GRP-R that is correctly coupled to the Ca2+ signaling pathway. Treatment of SW626 cells with bombesin, the amphibian equivalent of GRP, inhibited expression of the gastrin gene in a time- and dose-dependent fashion. The SW626 ovarian cancer cell line will provide a useful model to further define regulation and expression of both the gastrin gene and peptide in ectopic (nongastrointestinal) tissues.     

One hundred years of orthopedics in the Netherlands. IV. Spinal abnormalities]

In recent years there has been spectacular progress in the approach to various disorders of the spinal column. Owing to improved methods of osteosynthesis there is no longer so much need for long periods of postoperative bed rest. Of all the scolioses, idiopathic scoliosis is most common. The vast majority of these cases are not clinically significant. What is seen in the remaining cases if left untreated is a progression in the curvature during growth. Progressive idiopathic scoliosis can be effectively treated using conservative methods. Screening at school is an important part of this process. If the curvature proves progressive and skeletal growth is not complete a brace can be prescribed. Use of this strategy and form of treatment can avoid progression of the curvature and development of serious deformities. This conservative therapy has markedly reduced the need for corrective surgery. Scheuermann's disease is characterized by a fixed dorsal thoracic kyphosis. Progressive Scheuermann's kyphosis can be effectively treated using a brace. The majority of fractures of the vertebral bodies can be treated conservatively. However, serious fractures normally require surgical intervention. In the industrialised Western world, low back pain is a major health problem and the foremost cause of disability and unfitness for work. Low back pain caused by degenerative disease of the spinal column should be treated using a multidisciplinary approach. The development of advanced operative techniques and osteosynthesis methods has made it possible to treat metastases of the spine surgically. The effects of this treatment on the quality of life are encouraging.     

Antibiotic pharmacodynamics in cerebrospinal fluid

The CSF half-lives of lipophilic agents, such as quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (beta-lactams and vancomycin) in CSF often differ from those in serum. In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic antibiotics, such as beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of inflammation. In contrast, lipophilic antibiotics, such as quinolones, enter the CSF more efficiently and their penetration is not inflammation dependent. The pharmacodynamic properties of antibiotics in CSF are generally similar to those in other body sites; beta-lactam agents and vancomycin are time-dependent, whereas the quinolones and aminoglycosides are concentration-dependent. However, a notable difference from infections in other sites is that quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF, quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness. With the exception of quinolones, many antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in meningitis. However, this requires clinical verification.     

Transthoracic defibrillation of swine with monophasic and biphasic waveforms

BACKGROUND: Biphasic waveforms have had a favorable impact on internal defibrillation but have seen minimal use in transthoracic defibrillation systems. The purpose of this study was to compare monophasic and biphasic waveforms for transthoracic defibrillation in swine. METHODS AND RESULTS: Three interrelated studies were performed in 19 swine to establish the relative transthoracic defibrillation efficacy of biphasic shock waveforms. In study 1, we measured voltage (V50) and energy (E50) strength-duration curves for monophasic and biphasic truncated exponential waveforms. We then independently examined the effects of phase duration and tilt on biphasic waveform defibrillation with a total waveform duration from study 1 that provided the minimum V50 (study 2) and the minimum E50 (study 3). At each pulse duration tested in study 1, biphasic waveforms defibrillated with significantly less voltage and energy than monophasic waveforms. At a duration of 12 ms, there was a voltage minimum for biphasic waveform defibrillation. At this duration, V50 was 1378 +/- 505 V for the biphasic waveform compared with 2185 +/- 361 V for the monophasic waveform, P = .01. For both monophasic and biphasic waveforms, E50 increased with pulse duration. With a total pulse duration of 12 ms, E50 was 169 +/- 101 J for the biphasic waveform compared with 414 +/- 114 J for the monophasic waveform, P = .003. In study 2, optimization of phase duration and total tilt reduced the defibrillation requirements of the 12-ms "minimum voltage" biphasic waveform to 1284 +/- 187 V and 129 +/- 36 J. In study 3, the 8-ms "minimum energy" biphasic waveform had an E50 of 115 +/- 35 J that was 11% less than the 12-ms biphasic waveform, P = .11; however, voltage requirements of 1476 +/- 239 V were 15% higher, P = .005. CONCLUSIONS: This study demonstrates the superiority of truncated biphasic waveforms over truncated monophasic waveforms for transthoracic defibrillation of swine. Biphasic waveforms should prove as advantageous at reducing voltage and energy requirements for transthoracic defibrillation as they have for internal defibrillation.     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

Multidimensionality of oral health in dentate adults

OBJECTIVES: An understanding of the validity and usefulness of self-reported measures (as distinct from clinically determined measures) of oral health is emerging. These self-reported measures include self-rated oral health (SROH). Three objectives were to: (1) describe self-rated oral health in dentate adults, (2) quantify associations between self-rated oral health and other measures of oral health (oral disease and tissue damage, pain and discomfort, functional limitation, and disadvantage), and (3) assess the construct validity of a model of oral health proposed herein. METHODS: The Florida Dental Care Study is a longitudinal study of oral health, which included at baseline 873 subjects who had at least one tooth, were 45 years or older, and who participated for an interview and clinical examination. RESULTS: The prevalence of self-rated oral health decrements was substantial; approximately one fourth of subjects reported their oral health as only fair or poor. Bivariate and multivariate results provided consistent evidence of the construct validity of the proposed model of oral health. Additionally, the salience of one measure of dental appearance suggests that persons may use esthetic cues when rating their oral health. CONCLUSIONS: The proposed multidimensional model of oral health has construct validity. Self-rated oral health is affected by oral disease and tissue damage, oral pain and discomfort, oral functional limitation, and oral disadvantage. These self-reported measures and the proposed model should provide useful information for dental care effectiveness research. General health status has been disaggregated into the "physical" and the "mental;" an additional separation into the "oral" aspects of health seems warranted.     

Can cirrus clouds produce glories?

A vague glory display was photographed over central Utah from an airplane beginning its descent through a cirrus cloud layer with an estimated cloud top temperature of -45 and -55 degrees C. Photographic analysis reveals a single reddish-brown ring of 2.5-3.0 degrees radius around the antisolar point, although a second ring appeared visually to have been present over the brief observation period. Mie and approximate nonspherical theory scattering simulations predict a population of particles with modal diameters between 9 and 15 mum. Although it is concluded that multiple-ringed glories can be accounted for only through the backscattering of light from particles that are strictly spherical in shape, the poor glory colorization in this case could imply the presence of slightly aspherical ice particles. The location of this display over mountainous terrain suggests that it was generated by an orographic wave cloud, which we speculate produced numerous frozen cloud droplets that only gradually took on crystalline characteristics during growth.     

Choroidal neovascular membrane in Best's vitelliform macular dystrophy

The right eye of a 9-year-old white boy with Best's vitelliform macular dystrophy had an intact egg-yolk lesion and a retinal pigment epithelial defect superiorly, suggesting an early pseudohypopyon stage. The disruptive phase of the left eye showed subretinal hemorrhages, a "signet ring," and a subretinal neovascular membrane.     

Full-body interface pressure testing as a method for performance evaluation of clinical support surfaces

A method for evaluating the performance of clinical support surfaces is required by designers in their efforts to produce better clinical support surfaces that will reduce the incidence of pressure ulcers. In this study, a Pressure Index (P_index) is defined which is derived from an analytical equation used to evaluate the average interface pressure, the peak pressure, the magnitude of the peak pressure, and the number of peak pressures on the entire body. The type of subjects needed to represent a population of users as well as the head of bed elevations necessary to simulate clinical applications were integrated with the P_index to create a single-value mean pressure index which can be used to evaluate any type of surface. To determine the accuracy and repeatability of the mean pressure index, three surfaces (a standard hospital innerspring, a replacement foam mattress, and a low-airloss surface) were tested and evaluated using this method. The low airloss performed the best and the standard innerspring clearly performed the worst (p < 0.0001). The method appeared to accurately and reproducibly predict the relative performance of the three surfaces in reducing pressure.